Stroke awareness among community health workers from rural health blocks of Thiruvananthapuram, India.
Secondary prevention of stroke largely depends on risk factor control and lifestyle modification. Optimal secondary prevention strategies are limited in rural settings due to the shortage of primary care physicians and neurologists. Awareness of community health workers (CHWs) regarding stroke and its management remains largely unexplored. The current cross-sectional study aimed at assessing the knowledge, attitude, and practice (KAP) of CHWs regarding stroke care. A structured KAP questionnaire was administered among 510 CHWs from randomly selected rural health blocks of Thiruvananthapuram, Kerala, India. Knowledge assessment showed that the CHWs possessed an average knowledge of stroke care. The mean attitude and practice scores were higher, indicating a favorable attitude and good practice. The overall mean (standard deviation) KAP scores of CHWs were 13.54 (4.43) against a total score of 23. The KAP scores were highest among palliative care nurses. The stroke awareness of the accredited social health activists was comparatively lower than other CHWs. Factors such as age and years of work experience were not correlated to the KAP scores. Recurrent strokes remain a major challenge in primary care. Overall, the health workers demonstrated average knowledge, favorable attitudes, and positive practices. The study highlights the importance of training accredited social health activists (ASHAs) and other CHWs in stroke to improve secondary prevention strategies.


A mathematical model of antibody-dependent cellular cytotoxicity (ADCC).
Immunotherapies exploit the immune system to target and kill cancer cells, while sparing healthy tissue. Antibody therapies, an important class of immunotherapies, involve the binding to specific antigens on the surface of the tumour cells of antibodies that activate natural killer (NK) cells to kill the tumour cells. Preclinical assessment of molecules that may cause antibody-dependent cellular cytotoxicity (ADCC) involves co-culturing cancer cells, NK cells and antibody in vitro for several hours and measuring subsequent levels of tumour cell lysis. Here we develop a mathematical model of such an in vitro ADCC assay, formulated as a system of time-dependent ordinary differential equations and in which NK cells kill cancer cells at a rate which depends on the amount of antibody bound to each cancer cell. Numerical simulations generated using experimentally-based parameter estimates reveal that the system evolves on two timescales: a fast timescale on which antibodies bind to receptors on the surface of the tumour cells, and NK cells form complexes with the cancer cells, and a longer time-scale on which the NK cells kill the cancer cells. We construct approximate model solutions on each timescale, and show that they are in good agreement with numerical simulations of the full system. Our results show how the processes involved in ADCC change as the initial concentration of antibody and NK-cancer cell ratio are varied. We use these results to explain what information about the tumour cell kill rate can be extracted from the cytotoxicity assays.


How to Provide Nitrite Robustly for Anaerobic Ammonium Oxidation in Mainstream Nitrogen Removal.
Innovation in decarbonizing wastewater treatment is urgent in response to global climate change. The practical implementation of anaerobic ammonium oxidation (anammox) treating domestic wastewater is the key to reconciling carbon-neutral management of wastewater treatment with sustainable development. Nitrite availability is the prerequisite of the anammox reaction, but how to achieve robust nitrite supply and accumulation for mainstream systems remains elusive. This work presents a state-of-the-art review on the recent advances in nitrite supply for mainstream anammox, paying special attention to available pathways (forward-going (from ammonium to nitrite) and backward-going (from nitrate to nitrite)), key controlling strategies, and physiological and ecological characteristics of functional microorganisms involved in nitrite supply. First, we comprehensively assessed the mainstream nitrite-oxidizing bacteria control methods, outlining that these technologies are transitioning to technologies possessing multiple selective pressures (such as intermittent aeration and membrane-aerated biological reactor), integrating side stream treatment (such as free ammonia/free nitrous acid suppression in recirculated sludge treatment), and maintaining high activity of ammonia-oxidizing bacteria and anammox bacteria for competing oxygen and nitrite with nitrite-oxidizing bacteria. We then highlight emerging strategies of nitrite supply, including the nitrite production driven by novel ammonia-oxidizing microbes (ammonia-oxidizing archaea and complete ammonia oxidation bacteria) and nitrate reduction pathways (partial denitrification and nitrate-dependent anaerobic methane oxidation). The resources requirement of different mainstream nitrite supply pathways is analyzed, and a hybrid nitrite supply pathway by combining partial nitrification and nitrate reduction is encouraged. Moreover, data-driven modeling of a mainstream nitrite supply process as well as proactive microbiome management is proposed in the hope of achieving mainstream nitrite supply in practical application. Finally, the existing challenges and further perspectives are highlighted, i.e., investigation of nitrite-supplying bacteria, the scaling-up of hybrid nitrite supply technologies from laboratory to practical implementation under real conditions, and the data-driven management for the stable performance of mainstream nitrite supply. The fundamental insights in this review aim to inspire and advance our understanding about how to provide nitrite robustly for mainstream anammox and shed light on important obstacles warranting further settlement.


In vitro estrogen-binding by human breast carcinomas.
Patients whose breast carcinomas possess only low concentrations of a receptor molecule that binds estrogens with high affinity are unlikely to respond to hormonal manipulative therapy when the disease recurs. The estrogen-binding capacity of 106 breast carcinomas was measured by an in vitro method and was expressed per milligram wet weight and in some cases related to the concentration of deoxyribonucleic acid (DNA) of the tumours. The ability of tumors to bind 3H-estradiol ranged from 0 to 1.3 fm/mg in pre- and perenopausal women, and from 0 to 16.8 fm/mg in postmenopausal women. Menopausal status or serum concentrations of endogenous estrogen, or both, should therefore be considered when tumours are classified into low and high estrogen-binding capacity. It is not necessary to carry out Scatchard analysis for every tumour, and expressing estradiol binding on the basis of DNA concentration may be preferable to expressing in on a wet-weight basis.


Endometriosis is not associated with inferior pregnancy rates in in vitro fertilization: an analysis of 616 patients.
To analyze whether the presence of endometriosis per se is associated with inferior pregnancy rates in women undergoing in vitro fertilization (IVF). Between July 2005 and November 2012, a total of 485 patients with endometriosis under the age of 38 years undergoing their first IVF attempt at our center were included; 72 patients had minimal-mild disease and the remaining 413 patients had moderate-severe disease. 131 patients with laparoscopically confirmed tubal factor infertility not harboring endometriosis and hydrosalpinx under the age of 38 years undergoing their first IVF attempt at our center served as the control group. The bilateral antral follicle count and controlled ovarian hyperstimulation response were diminished in the moderate-severe group. However, the implantation, clinical pregnancy, miscarriage and live birth rates were comparable among the three groups. The recurrence of endometrioma following pre-IVF cystectomy was not associated with inferior pregnancy rates. Female age, bilateral antral follicle count and number of embryos transferred were noted to be significant independent predictors of live birth. We conclude that neither the presence nor the extent of endometriosis have any detrimental effect on IVF pregnancy rates.


Unexpected efficiency boosting in CO2-microemulsions: a cyclohexane depletion zone near the fluorinated surfactants evidenced by a systematic SANS contrast variation study.
Microemulsions with supercritical CO2 are promising alternatives for organic solvents, especially if both polar and non-polar components need to be dissolved. However, only fluorinated surfactants, which are known to be environmentally unfriendly, are appropriate to formulate well-structured microemulsions. While most approaches to increase the environmental performance of CO2-microemulsions deal with the design of new surfactants with a reduced degree of fluorination, we discovered that the partial substitution of CO2 by cyclohexane enables a considerable reduction of fluorinated surfactants. Thereby, the most efficient solubilization of the CO2/cyclohexane mixture, which turned out to be pressure-dependent, was found at a cyclohexane-to-CO2 mass ratio between 1 : 6 and 1 : 4. In order to elucidate this unexpected effect a systematic Small Angle Neutron Scattering (SANS) contrast variation study was performed. The analysis of the recorded scattering curves by the Generalized Indirect Fourier Transformation (GIFT) clearly shows that the scattering length density profiles differ considerably from CO2-microemulsions without cyclohexane. Instead of a nearly constant scattering length density, a density profile that varies systematically over half of the droplet radius was detected. These results clearly indicate that the observed efficiency boosting is caused by the formation of a depletion zone of cyclohexane close to the fluorinated amphiphilic film.


Maternal kangaroo (skin-to-skin) care in the NICU beginning 4 hours postbirth.
Kangaroo care (KC) for preterm infants is becoming well known in the United States. Typically, KC is given by mothers in the neonatal intensive care unit (NICU) beginning days or weeks postbirth. This case report documents KC beginning at 4.5 hours postbirth with a healthy mother whose 32-week, 1,953 gram infant required initial care in the NICU. The nurse's role in supporting this care is described. Both parents experienced KC with their son and were soon convinced of the exceptional benefits he received. The infant was transferred to intermediate care on Day 2, regained his birth weight by Day 12, was discharged home on Day 21. He was breast-feeding exclusively at 40 weeks corrected age, and had Bayley mental and motor development scores within normal limits at 6 months corrected age.


Fat grafting versus adipose-derived stem cell therapy: distinguishing indications, techniques, and outcomes.
With adipose-derived stem cells (ASCs) at the forefront of research and potential clinical applications, it is important that clinicians be able to distinguish them from the fat grafting currently used clinically and to understand how the two approaches relate to one another. At times, there has been confusion in clinically considering the two therapies to be the same. This report is aimed at distinguishing clearly between fat grafting and ASC therapy with regard to the indications, harvesting, processing, application techniques, outcomes, and complications. Findings have shown that autologous fat transfer, a widely used procedure for soft tissue augmentation, is beneficial for reconstructive and cosmetic procedures used to treat patients with volume loss due to disease, trauma, congenital defects, or the natural process of aging. On the other hand, ASCs have been identified as an ideal source of cells for regenerative medicine, with the potential to serve as soft tissue therapy for irradiated, scarred, or chronic wounds. Recent advances in tissue engineering suggest that the supplementation of fat grafts with ASCs isolated in the stromal vascular fraction may increase the longevity and quality of the fat graft. Research suggests that ASC supplementation may be a great clinical tool in the future, but more data should be acquired before clinical applications.


A climate change context for the decline of a foundation tree species in south-western Australia: insights from phylogeography and species distribution modelling.
A worldwide increase in tree decline and mortality has been linked to climate change and, where these represent foundation species, this can have important implications for ecosystem functions. This study tests a combined approach of phylogeographic analysis and species distribution modelling to provide a climate change context for an observed decline in crown health and an increase in mortality in Eucalyptus wandoo, an endemic tree of south-western Australia. Phylogeographic analyses were undertaken using restriction fragment length polymorphism analysis of chloroplast DNA in 26 populations across the species distribution. Parsimony analysis of haplotype relationships was conducted, a haplotype network was prepared, and haplotype and nucleotide diversity were calculated. Species distribution modelling was undertaken using Maxent models based on extant species occurrences and projected to climate models of the last glacial maximum (LGM). A structured pattern of diversity was identified, with the presence of two groups that followed a climatic gradient from mesic to semi-arid regions. Most populations were represented by a single haplotype, but many haplotypes were shared among populations, with some having widespread distributions. A putative refugial area with high haplotype diversity was identified at the centre of the species distribution. Species distribution modelling showed high climatic suitability at the LGM and high climatic stability in the central region where higher genetic diversity was found, and low suitability elsewhere, consistent with a pattern of range contraction. Combination of phylogeography and paleo-distribution modelling can provide an evolutionary context for climate-driven tree decline, as both can be used to cross-validate evidence for refugia and contraction under harsh climatic conditions. This approach identified a central refugial area in the test species E. wandoo, with more recent expansion into peripheral areas from where it had contracted at the LGM. This signature of contraction from lower rainfall areas is consistent with current observations of decline on the semi-arid margin of the range, and indicates low capacity to tolerate forecast climatic change. Identification of a paleo-historical context for current tree decline enables conservation interventions to focus on maintaining genetic diversity, which provides the evolutionary potential for adaptation to climate change.


Getting zeolite catalysts to play your tune: methyl carboxylate esters as switchable promoters for methanol dehydration to DME.
Methyl carboxylate esters can be used as additives to promote the zeolite catalysed formation of dimethly ether (DME) from methanol. By taking advantage of the well-known confinement effect in combination with further functionalisation the potency of the promoter can be markedly enhanced, giving significant increases in DME yield at promoter concentrations as low as 10 ppm relative to methanol. The promotion is readily reversible and promoter concentration can be used to fine tune the zeolite productivity to DME.


In vivo stable isotope labeling by amino acids in Drosophila melanogaster.
The fruit fly Drosophila melanogaster is one of the most widely used and well-studied model organisms in biology and therefore a promising tool for quantitative proteomics. Here, we describe a method to label D. melanogaster with stable isotope labeled amino acids in vivo. Feeding flies with heavy lysine labeled yeast cells leads to virtually complete heavy labeling already in the first filial generation. The approach is simple, fast, and cost-effective, which makes SILAC flies an attractive model system for the emerging field of in vivo quantitative proteomics.


3-Fluoro-2H-azirine: Generation, Characterization, and Photochemistry.
The elusive 3-fluoro-2H-azirine, cyclic NCH2CF, has been generated through the stepwise decomposition of the acryloyl azide CH2CFC(O)N3 in an N2-matrix at 10 K. The characterization of cyclic NCH2CF with matrix-isolation IR spectroscopy is supported by 15N isotope labeling and the calculations with density functional theory (DFT) at the B3LYP/6-311++G(3df,3pd) level of theory. Upon irradiation at 193 nm, cyclic NCH2CF undergoes ring opening by forming the more stable nitrile isomer CH2FCN. In contrast to the photodecomposition reactions, the high-vacuum flash pyrolysis of CH2CFC(O)N3 in the gas phase at 500 °C yields the Curtius rearrangement product CH2CFNCO along with secondary fragmentation to the atmospherically relevant fluorocarbonyl radical (FCO) and cyanomethyl radical (CH2CN). Calculations on the potential energy profile for the decomposition reactions of CH2CFC(O)N3 demonstrate that the excessive energy, arising from the highly exothermic Curtius rearrangement of the azide, plays a key role in driving further dissociation reactions of CH2CFNCO by overcoming the formidable barriers (>50 kcal mol-1) under the pyrolysis conditions.


CT-MRI Dual Information Registration for the Diagnosis of Liver Cancer: A Pilot Study Using Point-based Registration.
Early diagnosis of liver cancer may increase life expectancy. Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) play a vital role in diagnosing liver cancer. Together, both modalities offer significant individual and specific diagnosis data to physicians; however, they lack the integration of both types of information. To address this concern, a registration process has to be utilized for the purpose, as multimodal details are crucial in providing the physician with complete information. The aim was to present a model of CT-MRI registration used to diagnose liver cancer, specifically for improving the quality of the liver images and provide all the required information for earlier detection of the tumors. This method should concurrently address the issues of imaging procedures for liver cancer to fasten the detection of the tumor from both modalities. In this work, a registration scheme for fusing the CT and MRI liver images is studied. A feature point-based method with normalized cross-correlation has been utilized to aid in the diagnosis of liver cancer and provide multimodal information to physicians. Data on ten patients from an online database were obtained. For each dataset, three planar views from both modalities were interpolated and registered using feature point-based methods. The registration of algorithms was carried out by MATLAB (vR2019b, Mathworks, Natick, USA) on an Intel (R) Core (TM) i5-5200U CPU @ 2.20 GHz computer. The accuracy of the registered image is being validated qualitatively and quantitatively. The results show that an accurate registration is obtained with minimal distance errors by which CT and MRI were accurately registered based on the validation of the experts. The RMSE ranges from 0.02 to 1.01 for translation, which is equivalent in magnitude to approximately 0 to 5 pixels for CT and registered image resolution. The CT-MRI registration scheme can provide complementary information on liver cancer to physicians, thus improving the diagnosis and treatment planning process.


Lactobacillus amylovorus promotes lactose utilization in small 2 intestine by enhancing intestinal barrier function in intrauterine growth restricted piglets.
Intrauterine growth restriction (IUGR) resulted in high mortality and many physiological defects of piglets, causing huge economic loss in the swine industry. Lactobacillus amylovorus (L. amylovorus) was identified as one of the main differential bacteria between IUGR and normal piglets. However, the effects of L. amylovorus on the growth performance and intestinal health in IUGR piglets remained unclear. This study aimed to investigate the promoting effects of L. amylovorus Mafic1501, a new strain isolated from normal piglets, on the growth performance and intestinal barrier functions in IUGR piglets. Newborn mice or piglets were assigned into three groups: CON (normal birth weight, control), IUGR (low birth weight) and IUGR+L.amy (low birth weight), administered with sterile saline or L. amylovorus Mafic1501, respectively. Growth performance, lactose content in the digesta, intestinal lactose transporter and barrier function parameters were profiled. IPEC-J2 cells were cultured to verify the effects of L. amylovorus Mafic1501 on lactose utilization and intestinal barrier functions. L. amylovorus Mafic1501 elevated body weight and average daily gain of IUGR mice and piglets (P < 0.05). Lactose content in the ileum was decreased, whereas gene expression of glucose transporter 2 (GLUT2) was increased by L. amylovorus Mafic1501 in IUGR piglets during suckling period (P < 0.05). Besides, L. amylovorus Mafic1501 promoted intestinal barrier functions by increasing villus height and relative gene expressions of tight junctions (P < 0.05). L. amylovorus Mafic1501 and its culture supernatant decreased lactose level in the medium and upregulated gene expressions of transporter GLUT2 and tight junction protein Claudin-1 of IPEC-J2 cells (P < 0.05). L. amylovorus Mafic1501 improved the growth performance of IUGR piglets by promoting lactose utilization in small intestine and enhancing intestinal barrier functions. Our results provided new evidence of L. amylovorus Mafic1501 for its application in the swine industry.


Automatic detection of the boundary of the calcaneus from ultrasound parametric images using an active contour model; clinical assessment.
This paper presents a computerized method for automated detection of the boundary of the os calcis on in vivo ultrasound parametric images, using an active dynamic contour model. The initial contour, defined without user interaction, is an iso-contour extracted from the textural feature space. The contour is deformed through the action of internal and external forces, until stability is reached. The external forces, which characterize image features, are a combination of gray-level information and second-order textural features arising from local cooccurrence matrices. The broadband ultrasound attenuation (BUA) value is then averaged within the contour obtained. The method was applied to 381 clinical images. The contour was correctly detected in the great majority of the cases. For the short-term reproducibility study, the mean coefficient of variation was equal to 1.81% for BUA values and 4.95% for areas in the detected region. Women with osteoporosis had a lower BUA than age-matched controls (p = 0.0005). In healthy women, the age-related decline was -0.45 dB/MHz/yr. In the group of healthy post-menopausal women, years since menopause, weight and age were significant predictors of BUA. These results are comparable to those obtained when averaging BUA values in a small region of interest.


Psychometric properties of the DCD-Q-07 in children ages to 4-6.
It is important to identify Developmental Coordination Disorder (DCD) early in a child's life to allow for proper and timely intervention and support, and to reduce the negative secondary consequences associated with this condition. In this study we assessed the psychometric properties (construct validity, concurrent validity, reliability and test accuracy) of the Developmental Coordination Disorder Questionnaire (DCD-Q-07) in preschool children. A community-based sample of children ages 4-6 (n=181) were screened for motor difficulties using the Movement Assessment Battery for Children (M-ABC-2). Use of the M-ABC-2 resulted in the identification of 29 children below the 15th percentile, which we classified as probable DCD. Parents of these children concurrently completed the DCD-Q-07 to report their child's motor performance. The DCD-Q-07 demonstrated high internal consistency for both the full scale (alpha=0.881) and each subscale: control during movement (alpha=0.813), fine motor and handwriting (alpha=0.869) and general coordination (alpha=0.728). Moderate correlations (r=0.47-0.63) were also seen between the subscales on the DCD-Q-07, the strongest correlation being between control during movement and general coordination (r=0.63). Based on published age and sex cut points, the DCD-Q-07 showed poor sensitivity (20.7%) but high specificity (92.1%) against the M-ABC-2. Overall agreement with the M-ABC-2 was low using ROC analysis (area under the curve=0.654). Although it is important to screen for DCD in young children, the DCD-Q-07 may not be the best choice as a screening tool for DCD in preschool children ages 4-6 due to its low test accuracy.


Step-by-step calculation and spreadsheet tools for predicting stressor levels that extirpate genera and species.
In 2011, the United States Environmental Protection Agency (USEPA) released a field-based method for estimating the extirpation of freshwater aquatic benthic invertebrates by ionic mixtures dominated by HCO3- , SO42- , and Ca2+ measured as specific conductivity (SC). The estimate of extirpation was SC at the 95th centile (XC95) of a weighted cumulative frequency distribution (CFD) of a genus or species over a range of SC. A CFD of XC95 values was used to predict the SC at which 5% of genera were likely to be extirpated. Because there are many uses for XC95 values and many data sets that could be analyzed using this method, we laid out a step-by-step method for calculating XC95 values and the stressor level that predicts a 5% extirpation of genera (HC05). Although the calculations can be done with a handheld calculator, we developed 2 downloadable Microsoft Excel® spreadsheet calculation tools that are easy to use to calculate XC95 values, to plot a taxon's XC95 cumulative frequency distribution with increasing SC, and to plot probabilities of observing a taxon at a particular SC. They also plot cumulative frequency distributions of XC95 values and calculate HC05 values. In addition to the tools, we share an example and the output of XC95 values for 176 distinct aquatic benthic invertebrates in Appalachia, in West Virginia, USA. Integr Environ Assess Manag 2018;14:174-180. © 2017 SETAC.


Identification of a BALB/c H-2Ld gene by DNA-mediated gene transfer.
Gene transfer and immunoselection were used in the identification of a BALB/c genomic clone containing an H-2Ld gene (clone 27.5). Transformation of thymidine kinase-negative C3H mouse L cells with the cloned 27.5 DNA together with the herpes simplex virus tk gene produced transformants expressing Ld molecules detected by radioimmune assay with monoclonal hybridoma antibodies to Ld antigens. The foreign Ld gene products expressed by cloned mouse L cell transformants were shown to be virtually indistinguishable from BALB/c spleen Ld molecules by two-dimensional electrophoretic analysis of H-2Ld immunoprecipitates. These results indicate that the genomic clone 27.5 contains a functional BALB/c H-2Ld gene and demonstrate the usefulness of this approach for identifying the gene products encoded by cloned genes which are members of a multigene family. Furthermore, the ability to place cell-surface recognition molecules on the surfaces of foreign cells provides a powerful opportunity for functional analyses of these molecules.


Gfi1 ubiquitination and proteasomal degradation is inhibited by the ubiquitin ligase Triad1.
Growth factor independence 1 (Gfi1) is a transcriptional repressor essential for the function and development of many different hematopoietic lineages. The Gfi1 protein expression is regulated by the ubiquitin-proteasome system. In granulocytes, Gfi1 is rapidly degraded by the proteasome, while it is more stable in monocytes. How the ubiquitination and degradation of Gfi1 is regulated is unclear. Here, we show that the ubiquitin ligase Triad1 interacts with the DNA-binding domain of Gfi1. Unexpectedly, we found that Triad1 inhibited Gfi1 ubiquitination, resulting in a prolonged half-life. Down-regulation of endogenous Triad1 by siRNAs resulted in increased Gfi1 ubiquitination. In U937 cells, Triad1 caused an increase in endogenous Gfi1 protein levels and slowed cell proliferation in a similar manner when Gfi1 itself was expressed. A Triad1 mutant that lacks the Gfi1-binding domain did not affect Gfi1 levels and proliferation. Because neither proteasome-ubiquitin nor Triad1 ubiquitin ligase activity was required for the inhibition of Gfi1 ubiquitination, these data suggest that Triad1 competes for Gfi1 binding with as yet to be identified E3 ubiquitin ligases that do mark Gfi1 for proteasomal degradation. The fine-tuning of Gfi1 protein levels regulated by Triad1 defines an unexpected role for this protein in hematopoiesis.


Evidence for persistent hepatitis C virus (HCV) infection in hemophiliacs.
Hepatitis C virus (HCV) is the major etiologic agent associated with non-A, non-B hepatitis. This study was designed to assess virologic and serologic markers in hemophiliacs exposed to non-heat-treated and/or virus-inactivated plasma derivatives. Serial bleeds from 48 hemophilic patients were analyzed for the presence of HCV viral RNA sequences as detected by polymerase chain reaction (PCR) and antibodies to structural (core) and nonstructural (C-100 and 33C) proteins by specific dot immunoblot assay. All patients exposed to non-heat-treated products, and four of six patients exposed only to virus inactivated products, had evidence of HCV infection. However, over the 5-yr study period, six exposed patients (13%) consistently lacked detectable anti-C-100 and seven (15%) lost this antibody. HCV viremia (PCR positive) was found in 91% of exposed patients, and was significantly more frequent in HIV seropositive hemophiliacs (P less than 0.05). Six patients had high antibody level to HCV and elevated ALT, but appeared to clear viremia. Four hemophiliacs were HCV seropositive but lacked detectable viremia. These data indicate that hemophiliacs remain persistently infected by HCV and that antibody to the core antigen of HCV is a reliable marker of this transfusion transmissible agent.


Phase shift selection for two-step generalized phase-shifting interferometry.
A phase shift selection method is proposed to design algorithms immune against phase shift errors in two-step generalized phase-shifting interferometry. A general formula for wavefront reconstruction error is derived, and its specific expressions for two common errors are also given. Calculation results suggest that the proper range of phase shift for general application is about from 0.5 to 2.0 rad for both the fixed and linear phase shift errors. Computer simulations have demonstrated the effectiveness of this phase shift selection method by decreasing the wave reconstruction errors to one-fifth.


Usefulness of two-dimensional and speckle tracking echocardiography in "Gray Zone" left ventricular hypertrophy to differentiate professional football player's heart from hypertrophic cardiomyopathy.
Distinguishing the pathologic hypertrophy of hypertrophic cardiomyopathy (HC) from the physiologic hypertrophy of professional football players (PFP) can be challenging when septal wall thickness falls within a "gray zone" between 12 and 16 mm. It was hypothesized that 2-dimensional and speckle-tracking strain (ε) echocardiography could differentiate the hearts of PFPs from those of patients with HC with similar wall thicknesses. Sixty-six subjects, including 28 professional American football players and 21 patients with HC, with septal wall thicknesses of 12 to 16 mm, along with 17 normal controls, were studied using 2-dimensional echocardiography. Echocardiographic parameters, including modified relative wall thickness (RWT; septal wall thickness + posterior wall thickness/left ventricular end-diastolic diameter) and early diastolic annular tissue velocity (e'), were measured. Two-dimensional ε was analyzed by speckle tracking to measure endocardial and epicardial longitudinal ε and circumferential ε and radial cardiac ε. Septal wall thickness was higher in patients with HC than in PFPs (14.7 ± 1.1 vs 12.9 ± 0.9 mm, respectively, p <0.001), while posterior wall thickness showed no difference. RWT was larger in patients with HC than in PFPs (0.68 ± 0.10 vs 0.48 ± 0.06, p <0.001). Longitudinal endocardial ε and radial cardiac ε were significantly higher in PFPs than in patients with HC, while circumferential endocardial ε was no different. RWT was the parameter that most accurately differentiated PFPs from patients with HC. An RWT cut point of 0.6 differentiated PFPs from patients with HC, with an area under the curve of 0.97. In conclusion, a 2-dimensional echocardiographic measure of RWT (septal wall + posterior wall thickness/left ventricular end-diastolic dimension) accurately differentiated PFPs' hearts from those of patients with HC when septal wall thickness was in the gray zone of 12 to 16 mm. Two-dimensional strain analysis identifies variations in myocardial deformation between PFPs and patients with HC with gray-zone hypertrophy.


Stable isotope labeling of metal/metal oxide nanomaterials for environmental and biological tracing.
Engineered nanomaterials (NMs) are often compositionally indistinguishable from their natural counterparts, and thus their tracking in the environment or within the biota requires the development of appropriate labeling tools. Stable isotope labeling has become a well-established such tool, developed to assign 'ownership' or a 'source' to engineered NMs, enabling their tracing and quantification, especially in complex environments. A particular methodological challenge for stable isotope labeling is to ensure that the label is traceable in a range of environmental or biological scenarios but does not induce modification of the properties of the NM or lose its signal, thus retaining realism and relevance. This protocol describes a strategy for stable isotope labeling of several widely used metal and metal oxide NMs, namely ZnO, CuO, Ag, and TiO2, using isotopically enriched precursors, namely 67Zn or 68Zn metal, 65CuCl2, 107Ag or 109Ag metal, and 47TiO2 powder. A complete synthesis requires 1-8 d, depending on the type of NM, the precursors used, and the synthesis methods adopted. The physicochemical properties of the labeled particles are determined by optical, diffraction, and spectroscopic techniques for quality control. The procedures for tracing the labels in aquatic (snail and mussel) and terrestrial (earthworm) organisms and for monitoring the environmental transformation of labeled silver (Ag) NMs are also described. We envision that this labeling strategy will be adopted by industry to facilitate applications such as nanosafety assessments before NMs enter the market and environment, as well as for product authentication and tracking.


Retinoic acid induces sodium/iodide symporter gene expression and radioiodide uptake in the MCF-7 breast cancer cell line.
The sodium/iodide symporter (NIS) stimulates iodide uptake in normal lactating breast, but is not known to be active in nonlactating breast or breast cancer. We studied NIS gene regulation and iodide uptake in MCF-7 cells, an estrogen receptor (ER)-positive human breast cancer cell line. All-trans retinoic acid (tRA) treatment stimulated iodide uptake in a time- and dose-dependent fashion up to approximately 9.4-fold above baseline. Stimulation with selective retinoid compounds indicated that the induction of iodide uptake was mediated by retinoic acid receptor. Treatment with tRA markedly stimulated NIS mRNA and immunoreactive protein ( approximately 68 kDa). tRA stimulated NIS gene transcription approximately 4-fold, as shown by nuclear run-on assay. No induction of iodide uptake was observed with RA treatment of an ER-negative human breast cancer cell line, MDA-MB 231, or a normal human breast cell line, MCF-12A. The iodide efflux rate of tRA-treated MCF-7 cells was slow (t(1/2) = 24 min), compared with that in FRTL-5 thyroid cells (t(1/2) = 3.9 min), favoring iodide retention in MCF-7 cells. An in vitro clonogenic assay demonstrated selective cytotoxicity with (131)I after tRA stimulation of MCF-7 cells. tRA up-regulates NIS gene expression and iodide uptake in an ER-positive breast cancer cell line. Stimulation of radioiodide uptake after systemic retinoid treatment may be useful for diagnosis and treatment of some differentiated breast cancers.


[Incomplete hemolytic uremic syndrome associated with partial factor H deficiency].
Hemolytic uremic syndrome (HUS) consists of the association of hemolytic anemia, thrombocytopenia and renal failure. Most cases are related to toxins (verotoxins) produced by Escherichia coli 0157:H7 and generally have good renal prognosis. Atypical forms can occur, with a less favorable prognosis, and can be due to mutations in the gene codifying factor H, a protein that regulates activation of the alternative complement pathway, among other causes. Factor H deficiency produces continuous complement activation, causing injury to capillary endothelial cells. We report a case of incomplete (absence of thrombocytopenia and uremia), atypical HUS in which hypocomplementemia secondary to partial factor H deficiency was detected, with favorable outcome. Prior to symptom onset, the patient had a Campylobacter infection, precipitating the symptoms. Genetic analysis showed a heterozygous mutation (C846T) located in the SCR4 domain, generating an amino acid change in the factor H molecule (Pro240Leu). This mutation may have been the cause of the partial factor H deficiency and the patient's symptoms on admission.


Cholinergic stimulation alters performance and task-specific regional cerebral blood flow during working memory.
Modulation of the cholinergic neurotransmitter system results in changes in memory performance, including working memory (WM), in animals and in patients with Alzheimer disease. To identify associated changes in the functional brain response, we studied performance measures and regional cerebral blood flow (rCBF) using positron emission tomography (PET) in healthy subjects during performance of a WM task. Eight control subjects received an infusion of saline throughout the study and 13 experimental subjects received a saline infusion for the first 2 scans followed by a continuous infusion of physostigmine, an acetylcholinesterase inhibitor, for the subsequent 8 scans. rCBF was measured using H215O and PET in a sequence of 10 PET scans that alternated between rest and task scans. During task scans, subjects performed the WM task for faces. Physostigmine both improved WM efficiency, as indicated by faster reaction times, and reduced WM task-related activity in anterior and posterior regions of right midfrontal gyrus, a region shown previously to be associated with WM. Furthermore, the magnitudes of physostigmine-induced change in reaction time and right midfrontal rCBF correlated. These results suggest that enhancement of cholinergic function can improve processing efficiency and thus reduce the effort required to perform a WM task, and that activation of right prefrontal cortex is associated with task effort.


Electrogenic sodium-dependent bicarbonate secretion by glial cells of the leech central nervous system.
The ability to move acid/base equivalents across the membrane of identified glial cells was investigated in isolated segmental ganglia of the leech Hirudo medicinalis. The intracellular pH (pHi) of the glial cells was measured with double-barreled, neutral-ligand, ion-sensitive microelectrodes during step changes of the external pH (pHo 7.4-7.0). The rate of intracellular acidification after the decrease in extracellular pH (pHo) was taken as a measure of the rate of acid/base transport across the glial membrane. Taking into account the total intracellular buffering power, the maximum rate of acid/base flux was 0.4 mM/min in CO2/HCO3-free saline, and 3.92 mM/min in the presence of 5% CO2/10 mM HCO-3, suggesting that the acid/base flux was dependent upon HCO3-. The rate of acid influx/base efflux increased both with the external HCO3- concentration and with increasing pHi (and hence HCO3-i). This suggested that the decrease in pHi was due to HCO3- efflux. The rapid decrease of pHi was accompanied by a HCO3--dependent depolarization of the glial membrane from -74 +/- 5 mV (n = 20) to -54 +/- 7 mV (n = 13). Both this depolarization and the rate of intracellular acidification were greatly reduced by the anion exchange inhibitor 4,4-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS; 0.3-0.5 mM), but were not affected by the removal of external Cl-. Reduction of the external Na+ concentration to one-tenth normal affected the rate of intracellular acidification only in the presence of CO2/HCO3-: the rate increased within the first 3-5 min after lowering external Na+; after longer exposures in low external Na+ the rate decreased, presumably due to depletion of intracellular Na+. Amiloride (1 mM), which inhibits the Na+-H+ exchange in these cells, had no effect on the rate of intracellular acidification. The intracellular Na activity (aNai) of the glial cells was measured to be 5.2 +/- 1.0 mM (n = 8) in CO2/HCO3-free saline; aNai increased to 7.3 +/- 2.2 mM (n = 8) after the addition of 5% CO2/24 mM HCO3-. Upon a change in pHo to 7.0 in the presence of CO2/HCO3-, aNai decreased by an average of 2 +/- 1.1 mM (n = 5); in CO2/HCO3--free saline external acidification produced a transient increase in aNai. It is concluded that, in the presence of CO2/HCO3-, the rate of intracellular acidification in glial cells is dominated by an outwardly directed, electrogenic Na+-HCO3-cotransport. Neurons, which do not possess this cotransporter, acidify at much lower rates under similar conditions.(ABSTRACT TRUNCATED AT 400 WORDS)


Delayed occurrence of fatal neoplastic diseases in ames dwarf mice: correlation to extended longevity.
Ames dwarf mice have drawn much attention in aging research because of their marked life extension. Studies demonstrate that some of the physiological characteristics of Ames dwarf mice are similar to those of dietary restricted mice. Because dietary restriction has been shown to suppress and/or delay the occurrence of various age-related diseases, we investigated age-related pathological changes in Ames dwarf mice. We observed Ames dwarf mice to have a delayed occurrence of presumably fatal neoplastic disease compared with their normal siblings. In addition to the delayed occurrence, we found that the incidence of presumably fatal adenocarcinoma in lung was significantly lower in Ames dwarf mice than for their normal siblings. The delayed occurrence of total neoplastic lesions and reduced incidence of adenocarcinoma in lung possibly could be attributed to the retardation of tumor development by changes in the levels of growth hormone and insulin-like growth factor-1, and thereby be a major contributing factor to the extended life span observed in these mice.


Epidermal growth factor-like domain 7 promotes migration and invasion of human trophoblast cells through activation of MAPK, PI3K and NOTCH signaling pathways.
Epidermal growth factor-like domain 7 (Egfl7) is a gene that encodes a partially secreted protein and whose expression is largely restricted to the endothelia. We recently reported that EGFL7 is also expressed by trophoblast cells in mouse and human placentas. Here, we investigated the molecular pathways that are regulated by EGFL7 in trophoblast cells. Stable EGFL7 overexpression in a Jeg3 human choriocarcinoma cell line resulted in significantly increased cell migration and invasiveness, while cell proliferation was unaffected. Analysis of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways showed that EGFL7 promotes Jeg3 cell motility by activating both pathways. We show that EGFL7 activates the epidermal growth factor receptor (EGFR) in Jeg3 cells, resulting in downstream activation of extracellular regulated kinases (ERKs). In addition, we provide evidence that EGFL7-triggered migration of Jeg3 cells involves activation of NOTCH signaling. EGFL7 and NOTCH1 are co-expressed in Jeg3 cells, and blocking of NOTCH activation abrogates enhanced migration of Jeg3 cells overexpressing EGFL7. We also demonstrate that signaling through EGFR and NOTCH converged to mediate EGFL7 effects. Reduction of endogenous EGFL7 expression in Jeg3 cells significantly decreased cell migration. We further confirmed that EGFL7 stimulates cell migration by using primary human first trimester trophoblast (PTB) cells overexpressing EGFL7. In conclusion, our data suggest that in trophoblast cells, EGFL7 regulates cell migration and invasion by activating multiple signaling pathways. Our results provide a possible explanation for the correlation between reduced expression of EGFL7 and inadequate trophoblast invasion observed in placentopathies.


A radiochemical assay for glutamine synthetase, and activity of the enzyme in rat tissues.
1. A radiochemical assay for glutamine synthetase has been developed in which an ATP-regenerating system is incorporated to prevent accumulation of inhibitory amounts of ADP. It is particularly suitable for assay of the enzyme in crude tissue extracts containing high adenosine triphosphatase activity. 2. A survey of the distribution of the enzyme in tissues from normal male rats showed that activity is present in liver, brain cortex, kidney cortex, spleen, testis and retina. 3. The K(m) of the enzyme for l-glutamate is approx. 1.5x10(-2)m.


Genetic and environmental influences on the stability of withdrawn behavior in children: a longitudinal, multi-informant twin study.
We examined the contribution of genetic and environmental influences on the stability of withdrawn behavior (WB) in childhood using a longitudinal multiple rater twin design. Maternal and paternal ratings on the withdrawn subscale of the Child Behavior Checklist (CBCL) were obtained from 14,889 families when the twins were 3, 7, 10 and 12 years old. A longitudinal psychometric model was fitted to the data and the fit of transmission and common factor models were evaluated for each variance component. WB showed considerable stability throughout childhood, with correlation coefficients ranging from about .30 for the 9-year time interval to .65 for shorter time intervals. Individual differences in WB as observed by the mother and the father were found to be largely influenced by genetic effects at all four time points, in both boys (50-66%) and girls (38-64%). Shared environmental influences explained a small to modest proportion (0-24%) of the variance at all ages and were slightly more pronounced in girls. Non-shared environmental influences were of moderate importance to the variance and slightly increased with age, from 22-28% at age 3 to 35-41% at age 12 years. The stability of WB was largely explained by genetic effects, accounting for 74% of stability in boys and 65% in girls. Shared environmental effects explained 7% (boys) and 17% (girls) of the behavioral stability. Most shared environmental effects were common to both raters, suggesting little influence of rater bias in the assessment of WB. The shared environmental effects common to both raters were best described by a common factor model, indicating that these effects are stable and persistent throughout childhood. Non-shared environmental effects accounted for the remaining covariance over time.


Alternatives to neonatal intubation.
Opportunities to learn and maintain competence in neonatal intubation have decreased. As many clinicians providing care to the newborn infant are not skilled in intubation, alternative strategies are critical. Most preterm infants breathe spontaneously, and require stabilisation rather than resuscitation at birth. Use of tactile stimulation, deferred cord clamping, and avoidance of hypoxia can help optimise breathing for these infants. Nasal devices appear a promising alternative to the face mask for early provision of respiratory support. In term and near-term infants, supraglottic airways may be the most effective initial approach to resuscitation. Use of supraglottic airways during resuscitation can be taught to a range of providers, and may reduce need for intubation. While face mask ventilation is an important skill, it is challenging to perform effectively. Identification of the best approach to training the use of these devices during neonatal resuscitation remains an important priority.


Arthritis and systemic disease caused by Borrelia burgdorferi infection in a cow.
Infection with Borrelia burgdorferi caused arthritis, myocarditis, glomerulonephritis, and pneumonitis in a cow. Spirochetes were detected by use of immunofluorescent staining in liver and lung specimens and were isolated from the liver. The carpal, stifle, and tarsal joints had marked synovial proliferation, and synovial fluid obtained from these joints had high antibody titers against B burgdorferi. The cow was from an area of Wisconsin that is not endemic for borreliosis.


Adams-Oliver syndrome associated with cutis marmorata telangiectatica congenita and congenital cataract: a case report.
A female infant presented with Adams-Oliver syndrome (AOS), intrauterine growth retardation, severe cutis marmorata telangiectatica congenita, bilateral congenital cataract, and periventricular lesions. The here-reported association of bilateral congenital cataract with AOS is original. Adams-Oliver syndrome is a genetic defect that causes a vasculopathy and leads to a variety of phenotypes. This observation further supports the current understanding of the physiopathology of AOS.


Stretchable bioelectrodes.
In this paper, we present a stretchable electrode array for studying cell behavior subjected to mechanical strain. The electrode array consists of four gold nail-head pins (250 microm tip diameter and 1.75 mm spacing) inserted into a polydimethylsiloxane (PDMS) platform (25.4 x 25.4mm(2)). Fusible indium alloy (liquid at room temperature) filled microchannels are used to connect the electrodes to the outside, thus providing the required stretchability. The electrode platform is biocompatible and can withstand strains of up to 40%. We tested these electrodes by repeatedly (100 times) subjecting them to 35% strain and did not notice any failure. We also successfully cultured mice cardiomyocytes onto the platform and performed electrical pacing.


Pressure measurement in pancreatic duct and biliary duct system in dogs with acute pancreatitis.
We investigated the intraductal pressures of the pancreatico-biliary system in dogs with acute pancreatitis. Intraductal pressures were measured by the method of perfusion manometry. After the perfusion with saline (the common bile duct (CBD: 0.8 ml/min, the pancreatic duct (PD: 0.2 ml/min], two parameters, the residual pressure (RP) and the pressure decay time (DT), were measured before and after the induction of acute pancreatitis. The RP of the PD was elevated after inducing severe pancreatitis. There were statistically significant difference of the RP of the PD between severe and moderate pancreatitis. In addition the DT of the PD was also prolonged in severe pancreatitis. There were significant difference of the DT of the PD between moderate and severe pancreatitis. On the other hand the RP of the CBD was also elevated in severe pancreatitis. There were statistically significant difference of the RP of the CBD between severe and moderate pancreatitis. However there was no significant difference between them concerning the DT of the CBD. The histological examination of periampullary area in severe pancreatitis showed measurable inflammatory changes (papillitis). However there was no such finding in moderate pancreatitis. Our results suggest that pressure measurement in the PD is useful for predicting the severity of acute pancreatitis because the pressure of both the PD and the CBD were elevated in severe pancreatitis but not in moderate pancreatitis and this difference is mainly due to the difference of the influence of pancreatitis to the periampullary region.


Serum prostate-specific antigen as a predictor of prostate volume in the community: the Krimpen study.
Serum prostate-specific antigen (PSA) is considered a proxy for prostate volume (PV). This study investigates which range of PSA values has the best utility in the determination of PV (<30 cc, at 30, 40, and 50 cc), and whether PSA performs better than digital rectal examination (DRE) when estimating PV. In a population-based follow-up study of 1688 men in Krimpen aan den IJssel, The Netherlands, at baseline we estimated PV by DRE and by transrectal planimetric ultrasound (TRUS), in addition to measuring PSA. Men who tested positive for prostate cancer (PCa) at baseline and at 2 and 4 yr of follow-up were excluded from the analyses (n=142). Of the men without PCa, PSA and PV data were available in 1524 participants. Of all 1524 men analysed, 76.7% had a PSA of 0-2.0, 15.0% had a PSA of 2.1-4.0, and 8.3% a PSA>4. Low PSA ranges (0-2 and 2.1-4.0) discriminate better for a PV of 30 cc (eg, in men with a PSA range of 2.1-2.5 ng/ml there was a 72% chance of having a PV>30 cc). Higher ranges of PSA (>4.0) discriminate better for a PV>40 or 50 cc. (eg, in men with a PSA in the range of 4.1-7.0 ng/ml there was a 69% chance of having a PV>40 cc and in men with a PSA>10 ng/ml there was a 75% chance of a PV>50 cc). The receiver operating curve (ROC) for the performance of PSA in estimating a PV>30 cc shows an area under the curve (AUC) of 0.79, denoting reasonable discrimination, and AUCs of 0.86 and 0.92, denoting good discrimination of PVs>40 cc and >50 cc, respectively. PSA performed significantly better than DRE at estimating PV. Multiple regression analysis shows that both DRE and an interaction term for age and PSA provided minimal additional information beyond PSA in the prediction of PV; however, their contribution is numerically minimal/not clinically meaningful. In men for whom a diagnosis of PCa has been ruled out, PSA can be used to detect an enlarged prostate (>30 cc and with more accuracy PV>40 or 50 cc). More precision in estimating PV can be obtained when using a formula that contains PSA, age, DRE, and an interaction term between age and PSA; however, the clinical advantage of the formula over PSA alone is only modest as shown by the ROC curves. Thus, for clinicians looking for an easy and fast way to identify patients with an enlarged prostate, PSA is a good approximation for men without PCa.


Beyond the numbers: An in-depth look at Cameroon's fifth national COVID-19 vaccination campaign through geographical and gender lenses.
Cameroon has been struggling with low Covid-19 vaccination coverage, with only 4.5 % of the population receiving the primary series as of November 2022. The COVID-19 Vaccine Delivery Partnership (CoVDP) conducted a high-level mission to Cameroon to assess progress and advocate for actions to address bottlenecks. The objective of the mission was to administer at least 3,000,000 doses of vaccines during the 5th Mass vaccination campaign. This study examines the factors contributing to the success of the campaign and uses a geographical and gender lens to assess the results. The study is a secondary analysis of data from the DHIS2 collected during the 5th mass vaccination campaign for Covid-19. Descriptive statistics were used to assess coverages per location and gender expressed in OR. sccess factors, and chi-squared tests were used to assess differences in vaccine distribution across regions and by gender. This 5th vaccination campaign benefitted from a strong political commitment facilitated by CoVDP's mission, international support, collaboration, planning, supervision, and demand generation. The campaign recorded 2 019 118 administered vaccine doses, a staggering 46-fold increase in vaccinated individuals relative to the first round, with vaccination coverage reaching 10.1 % of the general population. However, the study reveals regional and gender disparities in vaccination coverage. Men had higher odds of being vaccinated than women in the three Sahel regions. Among individuals with comorbidities, the national coverage rate was only 14 %, and the Far North and East regions exhibited the lowest coverage rates. Janssen was the most used vaccine, and the total AEFI cases reported were 2 per 1000 vaccine doses. The 5th COVID-19 vaccination campaign in Cameroon saw a strong political commitment and was the most successful so far. Despite the gains, there was gender disparity in coverage in some regions. It is important to continue the established momentum, ensure equitable access in the Sahel regions, and reach high-priority groups with primary series and booster doses.


A phase 1, randomized, open-label, active-controlled trial to assess the safety of a meningococcal serogroup B bivalent rLP2086 vaccine in healthy adults.
Neisseria meningitidis serogroup B (MnB) is a significant cause of invasive meningococcal disease, but no broadly protective vaccine is yet approved. We assessed the safety and immunogenicity of a bivalent MnB vaccine composed of lipidated subfamily A and B variants of recombinant LP2086 (rLP2086, also known as factor H binding protein, fHBP). Forty-eight adults, ages 18-40 y, were randomized to receive 60, 120 or 200 μg of the bivalent rLP2086 vaccine or control at 0, 2 and 6 mo. Immunogenicity was assessed by rLP2086-specific immunoglobulin G (IgG) geometric mean titers for subfamily A and B proteins. Safety was determined by laboratory assessments of blood and urine and by reporting of solicited and unsolicited adverse events (AEs). The bivalent rLP2086 vaccine elicited high IgG titers following the second and third vaccination at all dose levels. In each of the four study arms, 11 of the 12 participating subjects reported ≥ 1 AE, and no serious AEs were reported. Local and systemic reactions were mainly mild to moderate. Laboratory abnormalities (including increased sodium, decreased neutrophils, and proteinuria) were not associated with clinical events and were not considered to be related to the study vaccine. Vaccinations were generally well-tolerated. Strong IgG antibody responses and the absence of clinically significant laboratory abnormalities support further development of the bivalent rLP2086 vaccine (www.clinicaltrials.gov; identifier: NCT00879814).


Discovering relevance knowledge in data: a growing cell structures approach.
Both information retrieval and case-based reasoning systems rely on effective and efficient selection of relevant data. Typically, relevance in such systems is approximated by similarity or indexing models. However, the definition of what makes data items similar or how they should be indexed is often nontrivial and time-consuming. Based on growing cell structure artificial neural networks, this paper presents a method that automatically constructs a case retrieval model from existing data. Within the case-based reasoning (CBR) framework, the method is evaluated for two medical prognosis tasks, namely, colorectal cancer survival and coronary heart disease risk prognosis. The results of the experiments suggest that the proposed method is effective and robust. To gain a deeper insight and understanding of the underlying mechanisms of the proposed model, a detailed empirical analysis of the models structural and behavioral properties is also provided.


Effects of prenatal yoga on women's stress and immune function across pregnancy: A randomized controlled trial.
The effects of prenatal yoga on biological indicators have not been widely studied. Thus, we compared changes in stress and immunity salivary biomarkers from 16 to 36 weeks' gestation between women receiving prenatal yoga and those receiving routine prenatal care. For this longitudinal, prospective, randomized controlled trial, we recruited 94 healthy pregnant women at 16 weeks' gestation through convenience sampling from a prenatal clinic in Taipei. Participants were randomly assigned to intervention (n=48) or control (n=46) groups using Clinstat block randomization. The 20-week intervention comprised two weekly 70-min yoga sessions led by a midwife certified as a yoga instructor; the control group received only routine prenatal care. In both groups, participants' salivary cortisol and immunoglobulin A levels were collected before and after yoga every 4 weeks from 16 to 36 weeks' gestation. The intervention group had lower salivary cortisol (p<0.001) and higher immunoglobulin A (p<0.001) levels immediately after yoga than the control group. Specifically, the intervention group had significantly higher long-term salivary immunoglobulin A levels than the control group (p=0.018), and infants born to women in the intervention group weighed more than those born to the control group (p<0.001). Prenatal yoga significantly reduced pregnant women's stress and enhanced their immune function. Clinicians should learn the mechanisms of yoga and its effects on pregnant women. Our findings can guide clinicians to help pregnant women alleviate their stress and enhance their immune function.


Residual number processing in dyscalculia.
Developmental dyscalculia - a congenital learning disability in understanding numerical concepts - is typically associated with parietal lobe abnormality. However, people with dyscalculia often retain some residual numerical abilities, reported in studies that otherwise focused on abnormalities in the dyscalculic brain. Here we took a different perspective by focusing on brain regions that support residual number processing in dyscalculia. All participants accurately performed semantic and categorical colour-decision tasks with numerical and non-numerical stimuli, with adults with dyscalculia performing slower than controls in the number semantic tasks only. Structural imaging showed less grey-matter volume in the right parietal cortex in people with dyscalculia relative to controls. Functional MRI showed that accurate number semantic judgements were maintained by parietal and inferior frontal activations that were common to adults with dyscalculia and controls, with higher activation for participants with dyscalculia than controls in the right superior frontal cortex and the left inferior frontal sulcus. Enhanced activation in these frontal areas was driven by people with dyscalculia who made faster rather than slower numerical decisions; however, activation could not be accounted for by response times per se, because it was greater for fast relative to slow dyscalculics but not greater for fast controls relative to slow dyscalculics. In conclusion, our results reveal two frontal brain regions that support efficient number processing in dyscalculia.


Transarterial Embolization of Iatrogenic Cystic Artery Pseudoaneurysm.
Cystic artery pseudoaneurysm (CAP) is a rare entity most often resulting from inflammatory conditions (acute cholecystitis or pancreatitis) or iatrogenic trauma (cholecystectomy). We report the case of a 73-year-old female who presented with abdominal pain and gastrointestinal bleeding after an episode of acute cholecystitis and endoscopic retrograde cholangiopancreatography for choledocolithiasis removal. Computed tomography and angiography revealed a CAP measuring 5 cm. A right hepatic artery transcatheter embolization was performed with glue, excluding the pseudoaneurysm. The next day, the patient underwent open cholecystectomy with ligation of the cystic artery. Later, ischemic hepatitis and abscess developed.


Acute Toxicity and Cytotoxicity of Pereskia aculeata, a Highly Nutritious Cactaceae Plant.
Pereskia aculeata is a Cactaceae plant with valuable nutritional properties, including terrific amounts of protein, minerals, vitamins, and fiber. However, P. aculeata is reported to contain antinutrients and alkaloids in its leaves. In addition, in a study on growth and development, Wistar rats fed with P. aculeata and casein as protein source grew less than the control group (fed with casein only). Therefore, in this study, we evaluated, for the first time, the oral acute toxicity of P. aculeata in rats and also the cytotoxicity behavior of the plant on lettuce seeds. The acute toxicity research was carried out using dried P. aculeata ethanolic extract, in three different doses, administered by gavage to 24 female Wistar rats. The rats were then examined for signs of toxicity, food intake, body weight, and fecal excretion fluctuations, as well as histopathological alterations, using eight different body tissues. The acute toxicity study did not show any difference among the groups in either clinical evaluation or histopathological analyses. For the cytotoxicity study, dried P. aculeata ethanolic extract was applied on lettuce seeds in five different concentrations. These seeds were evaluated for germination, root and shoot length, and mitotic index. The results show that P. aculeata extract affects lettuce root and shoot growth, but not germination or mitotic index. In conclusion, the acute toxicity on rats and the cytogenotoxicity on lettuce of P. aculeata are neglectable, validating the potential of this plant to be used as a functional food.


Layer-by-Layer Coatings of Collagen-Hyaluronic acid Loaded with an Antibacterial Manuka Honey Bioactive Compound to Fight Metallic Implant Infections.
Implant-associated severe infections can result in catastrophic implant failures; thus, advanced antibacterial coatings are needed to combat infections. This study focuses on harnessing nature-inspired self-assembly of extracellular matrix (ECM)-like coatings on Ti alloy with a combination of jellyfish-derived collagen (J-COLL) and hyaluronic acid (HA) using our customized automated hybrid layer-by-layer apparatus. To improve the anti-infection efficacy of coatings, we have incorporated a natural antibacterial agent methylglyoxal (MGO, a Manuka honey compound) in optimized multilayer coatings. The obtainment of MGO-loaded multilayer coatings was successfully assessed by profilometry, contact angle, attenuated total reflectance (ATR)-Fourier transform infrared spectroscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy. In vitro degradation confirmed the controlled release activity of MGO with a range of concentrations from 0.90 to 2.38 mM up to 21 days. A bacterial cell culture study using Escherichia coli (E. coli) and Staphylococcus epidermidis (S. epidermidis) confirmed that the MGO incorporated within layers 7 and 9 had a favorable effect on preventing bacterial growth and colonization on their surfaces. An in vitro cytocompatibility study confirmed that MGO agents included in the layers did not affect or reduce the cellular functionalities of L929 fibroblasts. In addition, MGO-loaded layers with Immortalized Mesenchymal Stem Cells (Y201 TERT-hMSCs) were found to favor the growth and differentiation of Y201 cells and promote calcium nodule formation. Overall, these surface coatings are promising candidates for delivering antimicrobial activity with bone-inducing functions for future bone tissue engineering applications.


Inhibition of vasopressin release to carotid occlusion by gamma-aminobutyric acid and glycine.
1 In cats anaesthetized with pentobarbitone sodium or chloralose, the amino acids, gamma-aminobutyric acid (GABA) and glycine, were applied to the ventral surface of the brain through paired Perspex rings placed across the medulla. 2 Applied to a region situated at the transition between medulla and cord, both amino acids greatly attenuated and even abolished the vasopressin release in response to carotid occlusion. Glycine was about 100 times more potent than GABA and effective in a concentration of 0.1 mg/ml. The pressor response to carotid occlusion was not affected. 3 Applied to a region situated 5 to 6 mm more rostrally, the amino acids did not affect vasopressin release but in strong concentrations, greatly attenuated the pressor response to carotid occlusion. 4 The two responses to carotid occlusion, vasopressin release and the pressor response, can thus be influenced independently. 5 It is concluded that the pathways carrying afferent impulses from the baroreceptors in the carotid sinus reach the ventral surface of the brain stem at two regions. At both, synaptic transmission can be blocked by the application of an inhibitory amino acid and thus prevent either the release of vasopressin at the caudal site, or the increase of vasomotor tone at the rostral site.


The distribution of benthic amphipod crustaceans in Indonesian seas.
Amphipod crustaceans are an essential component of tropical marine biodiversity. However, their distribution and biogeography have not been analysed in one of the world's largest tropical countries nested in the Coral Triangle, Indonesia. We collected and identified amphipod crustaceans from eight sites in Indonesian waters and combined the results with data from 32 additional sites in the literature. We analysed the geographic distribution of 147 benthic amphipod crustaceans using cluster analysis and the 'Bioregions Infomaps' neural network method of biogeographic discrimination. We found five groups of benthic amphipod crustaceans which show relationships with sampling methods, depth, and substrata. Neural network biogeographic analysis indicated there was only one biogeographic region that matched with the global amphipod regions and marine biogeographic realms defined for all marine taxa. There was no support for Wallaces or other lines being marine biogeographic boundaries in the region. Species richness was lower than expected considering the region is within the Coral Triangle. We hypothesise that this low richness might be due to the intense fish predation which may have limited amphipod diversification. The results indicated that habitat rather than biogeography determines amphipod distribution in Indonesia. Therefore, future research needs to sample more habitats, and consider habitat in conservation planning.


Predicting regional carbon price in China based on multi-factor HKELM by combining secondary decomposition and ensemble learning.
Accurately predicting carbon price is crucial for risk avoidance in the carbon financial market. In light of the complex characteristics of the regional carbon price in China, this paper proposes a model to forecast carbon price based on the multi-factor hybrid kernel-based extreme learning machine (HKELM) by combining secondary decomposition and ensemble learning. Variational mode decomposition (VMD) is first used to decompose the carbon price into several modes, and range entropy is then used to reconstruct these modes. The multi-factor HKELM optimized by the sparrow search algorithm is used to forecast the reconstructed subsequences, where the main external factors innovatively selected by maximum information coefficient and historical time-series data on carbon prices are both considered as input variables to the forecasting model. Following this, the improved complete ensemble-based empirical mode decomposition with adaptive noise and range entropy are respectively used to decompose and reconstruct the residual term generated by VMD. Finally, the nonlinear ensemble learning method is introduced to determine the predictions of residual term and final carbon price. In the empirical analysis of Guangzhou market, the root mean square error(RMSE), mean absolute error (MAE) and mean absolute percentage error (MAPE) of the model are 0.1716, 0.1218 and 0.0026, respectively. The proposed model outperforms other comparative models in predicting accuracy. The work here extends the research on forecasting theory and methods of predicting the carbon price.


Histamine H3 receptor-mediated suppression of inhibitory synaptic transmission in the submucous plexus of guinea-pig small intestine.
Conventional intracellular microelectrodes and marker injection techniques were used to study the actions of histamine on inhibitory synaptic transmission in the submucous plexus of guinea-pig small intestine. Bath application of histamine (1-300 microM) reversibly suppressed both noradrenergic and non-adrenergic slow inhibitory postsynaptic potentials in a concentration-dependent manner. These effects of histamine were mimicked by the selective histamine H(3) receptor agonist R(-)-alpha-methylhistamine but not the selective histamine H(1) receptor agonist, 6-[2-(4-imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl) heptanecarboxamide (HTMT dimaleate), or the selective histamine H(2) receptor agonist, dimaprit. The histamine H(3) receptor antagonist, thioperamide, blocked the effects of histamine. Histamine H(1) and H(2) receptor antagonists did not change the action of histamine. Hyperpolarizing responses to focal application of norepinephrine or somatostatin by pressure ejection from micropipettes were unaffected by histamine and R(-)-alpha-methylhistamine. The results suggest that histamine acts at presynaptic histamine H(3) receptors on the terminals of sympathetic postganglionic fibers and intrinsic somatostatinergic nerves in the small intestine to suppress the release of the inhibitory neurotransmitters, norepinephrine and somatostatin.


Observational study of the populations accessing rapid point-of-care HIV testing in Winnipeg, Manitoba, Canada, through a retrospective chart review of site records.
HIV point-of-care testing (POCT) has been available in Manitoba since 2008. This study evaluated the effectiveness of POCT at identifying individuals with previously unknown HIV status, its effects on clinical outcomes and the characteristics of the populations reached. A retrospective database review was conducted for individuals who received HIV POCT from 2011 to 2014. Time to linkage to care and viral load suppression were compared between individuals who tested positive for HIV using POCT and controls identified as positive through standard screening. Testing outcomes for labouring women with undocumented HIV status accessing POCT during labour were also assessed. 3204 individuals received POCT (1055 females (32.9%) and 2149 males (67.1%)), being the first recorded HIV test for 2205 (68.8%). Males were more likely to be targeted with POCT as their first recorded HIV test (adjusted OR (AOR) 1.40). Between the two main test sites (Main Street Project (MSP) and Nine Circles Community Health Centre), MSP tested relatively fewer males (AOR 0.79) but a higher proportion of members of all age groups over 30 years old (AOR 1.83, 2.51 and 3.64 for age groups 30-39, 40-49 and >50, respectively). There was no difference in time to linkage to care (p=0.345) or viral load suppression (p=0.405) between the POCT and standard screening cohorts. Of 215 women presenting in labour with unknown HIV status, one was identified as HIV positive. POCT in Manitoba has been successful at identifying individuals with previously unknown HIV-positive status. Demographic differences between the two main testing sites support that this intervention is reaching unique populations. Given that we observed no significant difference in time to clinical outcomes, it is reasonable to continue using POCT as a targeted intervention. HIV infection; rapid HIV testing; vertical infectious disease transmission; community outreach; service delivery; marginalised populations.


Phospholipid Molecular Layer that Enhances Distinction of Odors Based on Artificial Sniffing.
We propose a novel odor-sensing system based on the dynamic response of phospholipid molecular layers for artificial olfaction. Organisms obtain information about their surroundings based on multidimensional information obtained from sniffing, i.e., periodic perturbations. Semiconductor- and receptor-based odor sensors have been developed previously. However, these sensors predominantly identify odors based on one-dimensional information, which limits the type of odor molecule they can identify. Therefore, the development of odor sensors that mimic the olfactory systems of living organisms is useful to overcome this limitation. In this study, we developed a novel odor-sensing system based on the dynamics of phospholipids that responds delicately to chemical substances at room temperature using multidimensional information obtained from periodic perturbations. Odor molecules are periodically supplied to the phospholipid molecular layer as an input sample. The waveform of the surface tension of the phospholipid molecular layer changes depending on the odor molecules and serves as an output. Such characteristic responses originating from the dynamics of odor molecules on the phospholipid molecular layer can be reproduced numerically. The phospholipid molecular layer amplified the information originating from the odor molecule, and the mechanism was evaluated by using surface pressure-area isotherms. This paper offers a platform for an interface-chemistry-based artificial sniffing system as an active sensor and a novel olfactory mechanism via physicochemical responses of the receptor-independent membranes of the organism.


Long-term Risk of Colorectal Cancer and Related Death After Adenoma Removal in a Large, Community-based Population.
The long-term risks of colorectal cancer (CRC) and CRC-related death following adenoma removal are uncertain. Data are needed to inform evidence-based surveillance guidelines, which vary in follow-up recommendations for some polyp types. Using data from a large, community-based integrated health care setting, we examined the risks of CRC and related death by baseline colonoscopy adenoma findings. Participants at 21 medical centers underwent baseline colonoscopies from 2004 through 2010; findings were categorized as no-adenoma, low-risk adenoma, or high-risk adenoma. Participants were followed until the earliest of CRC diagnosis, death, health plan disenrollment, or December 31, 2017. Risks of CRC and related deaths among the high- and low-risk adenoma groups were compared with the no-adenoma group using Cox regression adjusting for confounders. Among 186,046 patients, 64,422 met eligibility criteria (54.3% female; mean age, 61.6 ± 7.1 years; median follow-up time, 8.1 years from the baseline colonoscopy). Compared with the no-adenoma group (45,881 patients), the high-risk adenoma group (7563 patients) had a higher risk of CRC (hazard ratio [HR] 2.61; 95% confidence interval [CI] 1.87-3.63) and related death (HR 3.94; 95% CI 1.90-6.56), whereas the low-risk adenoma group (10,978 patients) did not have a significant increase in risk of CRC (HR 1.29; 95% CI 0.89-1.88) or related death (HR 0.65; 95% CI 0.19-2.18). With up to 14 years of follow-up, high-risk adenomas were associated with an increased risk of CRC and related death, supporting early colonoscopy surveillance. Low-risk adenomas were not associated with a significantly increased risk of CRC or related deaths. These results can inform current surveillance guidelines for high- and low-risk adenomas.


Tryptophan metabolism in patients with breast cancer.
Plasma levels of total tryptophan were significantly lower in 51 patients with breast cancer than in 14 women with benign breast cancer following surgery and after 12 weeks. The urinary excretion of xanthurenic and 5-hydroxyindoleacetic acids were similar in patients with cancer and benign disease but the excretion of N'-methylnicotinamide (NMN) was significantly higher (P less than 0.001) in the cancer patients. It is suggested that the elevated urinary excretions of NMN is due to higher NAD activity reflecting elevated glycolysis through the Cori cycle.


Severe hypersensitivity to mosquito bites associated with natural killer cell lymphocytosis.
A 2-year-old girl showed exaggerated skin reactions to mosquito bites and associated general symptoms, including a high temperature, lymphadenopathy, and hepatosplenomegaly. Peripheral blood lymphocytes contained a high percentage of CD2+, CD3-, CD4-, CD8-, CD11b+, CD16+, CD38+, CD56+, CD57-, and HLA-DR+ large granular lymphocytes that exhibited a marked natural killer cell activity. Immunohistochemically, biopsy specimens taken from the lesional skin demonstrated an infiltrate of the cells bearing the natural killer cell phenotype, indicating a role of these cells in the development of the abnormal skin reactions to mosquito bites and other systemic manifestations. Our case suggests that natural killer cell lymphocytosis may show severe hypersensitivity to mosquito bites as the most outstanding manifestation.


Direct activation of mammalian atrial muscarinic potassium channels by GTP regulatory protein Gk.
The mammalian heart rate is regulated by the vagus nerve, which acts via muscarinic acetylcholine receptors to cause hyperpolarization of atrial pacemaker cells. The hyperpolarization is produced by the opening of potassium channels and involves an intermediary guanosine triphosphate-binding regulatory (G) protein. Potassium channels in isolated, inside-out patches of membranes from atrial cells now are shown to be activated by a purified pertussis toxin-sensitive G protein of subunit composition alpha beta gamma, with an alpha subunit of 40,000 daltons. Thus, mammalian atrial muscarinic potassium channels are activated directly by a G protein, not indirectly through a cascade of intermediary events. The G protein regulating these channels is identified as a potent Gk; it is active at 0.2 to 1 pM. Thus, proteins other than enzymes can be under control of receptor coupling G proteins.


Acute systemic inflammation reduces both carotid and aortic wave reflection in healthy adults.
Acute inflammation increases the risk of cardiac and cerebrovascular events, possibly related to alterations in the hemodynamic load. Wave reflection at the aorta and carotid provides insight into downstream vascular changes and hemodynamic load at the heart and brain. Acute inflammation has been suggested to reduce wave reflection via downstream vasodilation; however, this is not firmly established and has only been investigated at the aorta. We sought to explore the effect of acute inflammation on aortic and carotid hemodynamics in healthy, young adults. Pressure waveforms were collected via radial and carotid applanation tonometry in 23 adults (26 ± 4 years) before and 24 h after a typhoid vaccination. Waveforms were calibrated to brachial mean and diastolic pressure, and waveform separation analyses (WSA) were performed, yielding augmentation index, reflection index, time to reflection (Tr), forward (Pf) and reflected (Pb) wave magnitude, and pulse wave velocity. Arterial diameters and carotid stiffness were measured via ultrasonography. Acute inflammation reduced wave reflection at 24 h in both the aorta and carotid (P < 0.05) without changes in mean pressure. WSA did not reveal independent changes in Pf, Pb, or Tr (P > 0.05). Arterial stiffness did not change; however, brachial and carotid artery diameters increased. Acute inflammation reduces wave reflection in the aorta and carotid artery in young adults, potentially due to downstream/peripheral vasodilation. Reduced aortic wave reflection did not disturb the cardiac workload; however, reductions in carotid wave reflection may render the brain vulnerable to pulsatile hemodynamics. These findings may have implications for cardiac and cerebrovascular risk during acute inflammation.


Cell-matrix interactions and dynamic mechanical loading influence chondrocyte gene expression and bioactivity in PEG-RGD hydrogels.
The pericellular matrix (PCM) surrounding chondrocytes is thought to play an important role in transmitting biochemical and biomechanical signals to the cells, which regulates many cellular functions including tissue homeostasis. To better understand chondrocytes interactions with their PCM, three-dimensional poly(ethylene glycol) (PEG) hydrogels containing Arg-Gly-Asp (RGD), the cell-adhesion sequence found in fibronectin and which is present in the PCM of cartilage, were employed. RGD was incorporated into PEG hydrogels via tethers at 0.1, 0.4 and 0.8 mM concentrations. Bovine chondrocytes were encapsulated in the hydrogels and subjected to dynamic compressive strains (0.3 Hz, 18% amplitude strain) for 48h, and their response assessed by cell morphology, ECM gene expression, cell proliferation and matrix synthesis. Incorporation of RGD did not influence cell morphology under free swelling conditions. However, the level of cell deformation upon an applied strain was greater in the presence of RGD. In the absence of dynamic loading, RGD appears to have a negative effect on chondrocyte phenotype, as seen by a 4.7-fold decrease in collagen II/collagen I expressions in 0.8mM RGD constructs. However, RGD had little effect on early responses of chondrocytes (i.e. cell proliferation and matrix synthesis/deposition). When isolating RGD as a biomechanical cue, cellular response was very different. Chondrocyte phenotype (collagen II/collagen I ratio) and proteoglycan synthesis were enhanced with higher concentrations of RGD. Overall, our findings demonstrate that RGD ligands enhance cartilage-specific gene expression and matrix synthesis, but only when mechanically stimulated, suggesting that cell-matrix interactions mediate chondrocyte response to mechanical stimulation.


Synthesis and antimelanoma activity of reversed amide analogues of N-acetyl-4-S-cysteaminylphenol.
The melanin biosynthetic pathway from tyrosine is a potential target for combating malignant melanoma. N-Acetyl-4-S-cysteaminylphenol 1 is a previously synthesized analogue of tyrosine that probably acts by this pathway. It interferes with cell growth and proliferation via selective oxidation in melanocytes to an oquinone that can alkylate cellular nucleophiles. We previously synthesized a range of analogues of the original lead compound 1 most of which displayed greater cytotoxicity than 1. Eighteen new analogues with the amide group reversed have now been synthesized and tested for antimelanoma activity. Most of these reverse amides showed greater cytotoxicity than N-acetyl-4-S-cysteaminylphenol towards five representative melanoma cell lines. The highest cytotoxicity was observed for the piperidine and hexamethyleneimine derivatives 7, 8, 12, 13, and 17 and the catechol 18. The most active compound, 7, had cytotoxicity comparable to cisplatin against the five melanoma cell lines. The moderate activity of 7 and 18 against SK-Mel-24 (non-tyrosinase containing) and an ovarian cell line suggests that interference with the melanin pathway may not be the only mode of action of these compounds. Assays of some of the compounds as substrates for tyrosinase showed that the catechol 18 was the best substrate and that the piperidine derivative 7 was the best substrate of the phenolic compounds synthesized.


Mitochondrion: an emerging platform critical for host antiviral signaling.
Toll-like receptors (TLRs) and cytoplasmic retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are the two major receptor systems for detecting RNA viruses. RLRs play essential roles within the cytosol of various cell types. The signaling pathways converge at the mitochondrial antiviral signalling protein (MAVS) on the outer membrane of mitochondria. Recent research has surprisingly shown that many mitochondrial intrinsic factors play novel functions in RLR signaling, conferring a new perspective of therapeutic drug design to inhibit viral infection. This review covers the literature of the past 6 years and summarizes the components, regulation and mechanisms of RLR signaling, highlighting the function and regulation of mitochondrial proteins, such as MAVS and translocase of outer membrane (Tom)70 in this process. The authors attempt to delineate the complicated cross-talk among subcellular organelles in the context of intracellular antiviral signaling. It is imperative to elucidate the specific roles and mechanisms of post-translational modifications in MAVS signaling. The sub-cellular dynamics of regulatory proteins should be correlated with their multiple functions. Animal models are needed to further probe the integration of mitochondria with innate immunity evolutionarily; they will be instrumental for identifying novel antiviral targets and, ultimately, for developing specific clinical drugs.


Compliance with iron-folic acid (IFA) therapy among pregnant women in an urban area of south India.
Anaemia is highly prevalent among pregnant women and iron deficiency is the most important cause. Like many other countries, India has policies to give pregnant women iron supplements. Non-compliance is one important challenging factor in combating anaemia. To estimate the compliance for IFA tablets among pregnant women and to study the social factors influencing it. This study included 190 pregnant women seeking ante-natal care in tertiary health centres in the Mangalore city in south India. After Institutional Ethics Committee (IEC) approval, data was collected by personal interview. Missing >2 doses consecutively was considered non-compliance. The data was analyzed using SPSS (Statistical Package for Social Sciences) version 11.5. The mean age of the study population was 25.8 years (SD: 4.1). Most of the subjects consumed mixed diet and 72.1% belonged to lower socioeconomic status. Overall, compliance with IFA tablets was 64.7%. Compliance increased with the increase in age, birth order and single daily dose. Forgetfulness and both perceived as well as experienced side effects of IFA therapy were the important factors for non-compliance. There was a moderate level of compliance towards IFA tablets with key social and demographic factors playing an important role.


Fish Liver Discards as a Source of Long-Chain Omega-3 Polyunsaturated Fatty Acids.
The intake of omega-3 polyunsaturated fatty acids (PUFA) of the average consumer is generally low, and products such as fish oils high in omega-3 PUFA have become popular dietary supplements. There is a need for more sources of omega-3 PUFA to cover the increasing demand. This study investigated whether livers from different lean fish species could be a potential new source of oils rich in omega-3 PUFA. The seasonal variation in lipid content, fatty acid composition, peroxide value and free fatty acid content (FFA) of livers from cod, hake, ling, coalfish and monkfish was determined, and the effect of storage conditions on the fishing vessel (ice vs frozen) was studied. Generally, the lipid content and composition of the livers from the five fish species varied similarly during the two years of the sampling period, with significantly lower values in spring (March, April) and higher values in fall (October, November). Storage conditions were found to have no significant effect on the quality and oil composition. Monkfish livers were less suitable for production of omega-3 oil due to their lower lipid and EPA content as well as higher FFA levels. Coalfish had higher fluctuations in oil composition during the sampling period, which potentially makes a standardised quality difficult to obtain. Cod, hake and ling were the most suitable species for fish liver oil production.


A study of the directional response of ultraviolet radiometers: I. Practical evaluation and implications for ultraviolet measurement standards.
The directional responses of a range of ultraviolet radiometers commonly used for irradiance measurements of UVB and UVC have been studied. Radiometers with 24 diffuser/filter combinations were assessed using a deuterium source, and three different diffuser/filter designs were assessed using a monochromatic source. The directional responses of the radiometers have been calculated and expressed in terms of figures of merit similar to those described for (photopic) illuminance meters in BS 667 and CIE 69. Those radiometers that performed best for the measurement of both small and extended sources of UVB and UVC had raised PTFE diffusers. We conclude that UV radiometers with a directional response error f2 < 10% are readily available commercially, and that it would be appropriate for future ultraviolet standards to set an upper limit of 5% on f2. This would ensure that the overall uncertainty in irradiance measurements of extended ultraviolet sources is not dominated by the error in the directional response of the radiometer.


The function of chloroplast ferredoxin-NADP+ oxidoreductase positively regulates the accumulation of bamboo mosaic virus in Nicotiana benthamiana.
A gene down-regulated in Nicotiana benthamiana after bamboo mosaic virus (BaMV) infection had high identity to the nuclear-encoded chloroplast ferredoxin NADP+ oxidoreductase gene (NbFNR). NbFNR is a flavoenzyme involved in the photosynthesis electron transport chain, catalysing the conversion of NADP+ into NADPH. To investigate whether NbFNR is involved in BaMV infection, we used virus-induced gene silencing to reduce the expression of NbFNR in leaves and protoplasts. After BaMV inoculation, the accumulation of BaMV coat protein and RNA was significantly reduced. The transient expression of NbFNR fused with orange fluorescent protein (OFP) localized in the chloroplasts and elevated the level of BaMV coat protein. These results suggest that NbFNR could play a positive role in regulating BaMV accumulation. Expressing a mutant that failed to translocate to the chloroplast did not assist in BaMV accumulation. Another mutant with a catalytic site mutation could support BaMV accumulation to some extent, but accumulation was significantly lower than that of the wild type. In an in vitro replication assay, the replicase complex with FNR inhibitor, heparin, the RdRp activity was reduced. Furthermore, BaMV replicase was revealed to interact with NbFNR in yeast two-hybrid and co-immunoprecipitation experiments. Overall, these results suggest that NbFNR localized in the chloroplast with functional activity could efficiently assist BaMV accumulation.


A district general hospital's experience of hip resurfacing.
In our unit 180 consecutive hip resurfacing procedures have been performed. All patients had a posterior approach to the hip joint, followed by standard resurfacing using metal-on-metal components. The patients were evaluated radiographically and clinically preoperatively and postoperatively. The mean age of patients was 56 years (range 25-75). There was a statistically significant improvement between the preoperative Harris Hip Score and those at the latest follow-up. There were four fractures of the femoral neck; one was intra-operative and was converted to total joint arthroplasty. Three further fractures occurred: two were revised and one was treated non-operatively. There were no cases of dislocation or deep infection. The short- and medium-term results that have been achieved in this district general hospital are comparable to those that have been achieved in the originator's institution.


Utilization of the indirect lysosome targeting pathway by lysosome-associated membrane proteins (LAMPs) is influenced largely by the C-terminal residue of their GYXXphi targeting signals.
A systematic study was conducted on the requirements at the C-terminal position for the targeting of LAMPs to lysosomes, examining the hypothesis that a bulky hydrophobic residue is required. Mutations deleting or replacing the C-terminal valine with G, A, C, L, I, M, K, F, Y, or W were constructed in a reporter protein consisting of the lumenal/extracellular domain of avian LAMP-1 fused to the transmembrane and cytoplasmic domains of LAMP-2b. The steady-state distribution of each mutant form in mouse L-cells was assessed by quantitative antibody binding assays and immunofluorescence microscopy; efficiency of internalization from the plasma membrane and delivery to the lysosome were also estimated. It is found that (a) only C-terminal V, L, I, M, and F mediated efficient targeting to lysosomes, demonstrating the importance hydrophobicity and an optimal size of the C-terminal residue in targeting; (b) efficiency of lysosomal targeting generally correlated with efficiency of internalization; and (c) mutant forms that did not target well to lysosomes showed unique distributions in cells rather than simply default accumulation in the plasma membrane. Interactions of the targeting signals with adaptor subunits were measured using a yeast two-hybrid assay. The results are consistent with the hypothesis that trafficking of LAMP forms in cells through the indirect pathway is determined by the affinities of their targeting signals, predominantly for the mu2 and mu3 adaptors involved at plasma membrane and endosomal cellular sorting sites, respectively.


Reciprocal regulation of eNOS, H2S and CO-synthesizing enzymes in human atheroma: Correlation with plaque stability and effects of simvastatin.
The molecular and cellular mechanisms underlying plaque destabilization remain obscure. We sought to elucidate the correlation between NO, H2S and CO-generating enzymes, nitro-oxidative stress and plaque stability in carotid arteries. Carotid atherosclerotic plaques were collected from 62 patients who had undergone endarterectomy due to internal artery stenosis. Following histological evaluation the plaques were divided into stable and unstable ones. To investigate the impact of simvastatin we divided patients with stable plaques, into those receiving and to those not receiving simvastatin. Expression and/or levels of p-eNOS/eNOS, pAkt/t-Akt, iNOS, cystathionine beta synthase (CBS), cystathionine gamma lyase (CSE), heme oxygenase-1(HO-1), soluble guanyl cyclase sGCα1, sGCβ1, NOX-4 and HIF-1α were evaluated. Oxidative stress biomarkers malondialdehyde (MDA) and nitrotyrosine (NT) were measured. NT levels were decreased in stable plaques with a concomitant increase of eNOS phosphorylation and expression and Akt activation compared to unstable lesions. An increase in HIF-1α, NOX-4, HO-1, iNOS, CBS and CSE expression was observed only in unstable plaques. 78% of patients under simvastatin were diagnosed with stable plaques whereas 23% of those not receiving simvastatin exhibited unstable plaques. Simvastatin decreased iNOS, HO-1, HIF-1α and CSE whilst it increased eNOS phosphorylation. In conclusion, enhanced eNOS and reduced iNOS and NOX-4 were observed in stable plaques; CBS and CSE positively correlated with plaque vulnerability. Simvastatin, besides its known effect on eNOS upregulation, reduced the HIF-1α and its downstream targets. The observed changes might be useful in developing biomarkers of plaque stability or could be targets for pharmacothepary against plaque vulnerability.