Ultracytochemical localization of ATP-hydrolysing activity in vegetative cells, spores and isolated cytoplasmic membranes of Bacillus subtilis 168.
The localization of ATP-hydrolysing activity in vegetative cells, spores and isolated membranes of Bacillus subtilis 168 was studied by a cytochemical method combined with electron microscopy. The activity was located mainly in the cytoplasmic membrane and the mesosomes, and was also found in the inner layer of the cell wall facing the cytoplasmic membrane. Activity was also detected in the cross-membranes of dividing cells and in spore coats. The product of the reaction was observed either as fine electron-dense granules incorporated into the membranes, or as high-contrast lead precipitates on the surfaces of the membranes.


Targeted Codelivery of Prodigiosin and Simvastatin Using Smart BioMOF: Functionalization by Recombinant Anti-VEGFR1 scFv.
Biological metal-organic frameworks (BioMOFs) are hybrid compounds in which metal nodes are linked to biocompatible organic ligands and have potential for medical application. Herein, we developed a novel BioMOF modified with an anti-VEGFR1 scFv antibody (D16F7 scFv). Our BioMOF is co-loaded with a combination of an anticancer compound and a lipid-lowering drug to simultaneously suppress the proliferation, growth rate and metastases of cancer cells in cell culture model system. In particular, Prodigiosin (PG) and Simvastatin (SIM) were co-loaded into the newly synthesized Ca-Gly BioMOF nanoparticles coated with maltose and functionalized with a recombinant maltose binding protein-scFv fragment of anti-VEGFR1 (Ca-Gly-Maltose-D16F7). The nanoformulation, termed PG + SIM-NP-D16F7, has been shown to have strong active targeting behavior towards VEGFR1-overexpresing cancer cells. Moreover, the co-delivery of PG and SIM not only effectively inhibits the proliferation of cancer cells, but also prevents their invasion and metastasis. The PG + SIM-NP-D16F7 nanocarrier exhibited stronger cytotoxic and anti-metastatic effects compared to mono-treatment of free drugs and drug-loaded nanoparticles. Smart co-delivery of PG and SIM on BioMOF nanoparticles had synergistic effects on growth inhibition and prevented cancer cell metastasis. The present nanoplatform can be introduced as a promising tool for chemotherapy compared with mono-treatment and/or non-targeted formulations.


Brucellosis Transmission between Wildlife and Livestock in the Greater Yellowstone Ecosystem: Inferences from DNA Genotyping.
The wildlife of the Greater Yellowstone Ecosystem carries brucellosis, which was first introduced to the area by cattle in the 19th century. Brucellosis transmission between wildlife and livestock has been difficult to study due to challenges in culturing the causative agent, Brucella abortus . We examined B. abortus transmission between American bison ( Bison bison ), Rocky Mountain elk ( Cervus elaphus nelsoni), and cattle ( Bos taurus ) using variable number tandem repeat (VNTR) markers on DNA from 98 B. abortus isolates recovered from populations in Idaho, Montana, and Wyoming, US. Our analyses reveal interspecies transmission. Two outbreaks (2007, 2008) in Montana cattle had B. abortus genotypes similar to isolates from both bison and elk. Nevertheless, similarity in elk and cattle isolates from the 2008 outbreak suggest that elk are the likely source of brucellosis transmission to cattle in Montana and Wyoming. Brucella abortus isolates from sampling in Montana appear to be divided in two clusters: one found in local Montana elk, cattle, and bison; and another found mainly in elk and a bison from Wyoming, which is consistent with brucellosis having entered Montana via migration of infected elk from Wyoming. Our findings illustrate complex patterns of brucellosis transmission among elk, bison, and cattle as well as the utility of VNTRs to infer the wildlife species of origin for disease outbreaks in livestock.


Wildlife tracking data management: a new vision.
To date, the processing of wildlife location data has relied on a diversity of software and file formats. Data management and the following spatial and statistical analyses were undertaken in multiple steps, involving many time-consuming importing/exporting phases. Recent technological advancements in tracking systems have made large, continuous, high-frequency datasets of wildlife behavioural data available, such as those derived from the global positioning system (GPS) and other animal-attached sensor devices. These data can be further complemented by a wide range of other information about the animals' environment. Management of these large and diverse datasets for modelling animal behaviour and ecology can prove challenging, slowing down analysis and increasing the probability of mistakes in data handling. We address these issues by critically evaluating the requirements for good management of GPS data for wildlife biology. We highlight that dedicated data management tools and expertise are needed. We explore current research in wildlife data management. We suggest a general direction of development, based on a modular software architecture with a spatial database at its core, where interoperability, data model design and integration with remote-sensing data sources play an important role in successful GPS data handling.


Uncovering novel cell cycle players through the inactivation of securin in budding yeast.
Budding yeast securin/Pds1p, an inhibitor of the anaphase activator separase/Esp1p, is involved in several checkpoint pathways and in promoting Esp1p's nuclear localization. Using a modified synthetic genetic array (SGA) screen for genes that become essential in the absence of Pds1p, we uncovered roles for uncharacterized genes in cell cycle processes, including Esp1p activation.


Mathematical modeling and experimental breakthrough curves of carbon dioxide adsorption on metal organic framework CPM-5.
It is essential to capture carbon dioxide from flue gas because it is considered one of the main causes of global warming. Several materials and different methods have been reported for CO2 capturing including adsorption onto zeolites and porous membranes, as well as absorption in amine solutions. All such methods require high energy input and high cost. A new class of porous materials called Metal Organic Frameworks (MOFs) exhibited excellent performance in extracting carbon dioxide from a gas mixture. In this study, the breakthrough curves for the adsorption of carbon dioxide on CPM-5 (crystalline porous materials) were obtained experimentally and theoretically using a laboratory-scale fixed-bed column at different experimental conditions such as feed flow rate, adsorption temperature, and feed concentration. It was found that the CPM-5 has a dynamic CO2 adsorption capacity of 11.9 wt % (2.7 mmol/g) (corresponding to 8 mL/min, 298 K, and 25% v/v CO2). The tested CPM-5 showed an outstanding adsorption equilibrium capacity (e.g., 2.3 mmol/g (10.2 wt %) at 298 K) compared to other adsorbents, which can be considered as an attractive adsorbent for separation of CO2 from flue gas.


Comparison of albumin-mediated release of lysophosphatidylcholine and lysophosphatidylethanolamine from cultured rat hepatocytes.
We have investigated the albumin-stimulated release from cultured rat hepatocytes of lysophosphatidylcholine derived from methylation of phosphatidylethanolamine and of lysophosphatidylethanolamine. In the absence [corrected] of albumin, neither lysophosphatidylethanolamine nor lysophosphatidylcholine was released into the culture medium. Albumin stimulated the accumulation of both phospholipids in the medium. After 2 h, 14.1 nmol of lysophosphatidylcholine and 2.0 nmol of lysophosphatidylethanolamine per 3 x 10(6) cells had accumulated in the medium. The rate of release of [3H]ethanolamine-labelled lysophosphatidylethanolamine was rapid in the first 2 h and then was decreased, whereas there was a 1 h lag in the release of [3H]ethanolamine-labelled lysophosphatidylcholine. This apparent lag probably reflected the time necessary for the synthesis of phosphatidylcholine from phosphatidylethanolamine in the cells. Albumin caused a decrease in labelled cellular lysophosphatidylethanolamine and lysophosphatidylcholine which only partially accounted for the accumulation of the labelled phospholipids in the medium. Albumin also stimulated the release of labelled phosphatidylethanolamine (almost 3-fold) and phosphatidylcholine (2-fold) into the medium. There was no detectable change in the labelling of the cellular pools of these phospholipids, most likely owing to the large amounts in the cells compared with the medium. The labelled lysophospholipids did not arise from catabolism of the parent phospholipid in the medium. Analysis of the fatty acids of the secreted lysophospholipids showed a preferential release of unsaturated fatty acyl species of lysophosphatidylcholine, whereas lysophosphatidylethanolamine contained similar amounts of saturated and unsaturated fatty acids.


The ACCEPT-study: design of an RCT with an active treatment control condition to study the effectiveness of the Dutch version of PEERS® for adolescents with autism spectrum disorder.
Social skills interventions are commonly deployed for adolescents with autism spectrum disorder (ASD). Because effective and appropriate social skills are determined by cultural factors that differ throughout the world, the effectiveness of these interventions relies on a good cultural fit. Therefore, the ACCEPT study examines the effectiveness of the Dutch Program for the Education and Enrichment of Relational Skills (PEERS®) social skills intervention. This study is a two-arm parallel group randomized controlled trial (RCT) in which adolescents are randomly assigned (after baseline assessment) to one of two group interventions (PEERS® vs. active control condition). In total, 150 adolescents are to be included, with multi-informant involvement of their parents and teachers. The ACCEPT study uses an active control condition (puberty psychoeducation group training, focussing on social-emotional development) and explores possible moderators and mediators in improving social skills. The primary outcome measure is the Contextual Assessment of Social Skills (CASS). The CASS assesses social skills performance in a face to face social interaction with an unfamiliar, typically developing peer, making this a valuable instrument to assess the social conversational skills targeted in PEERS®. In addition, to obtain a complete picture of social skills, self-, parent- and teacher-reported social skills are assessed using the Social Skills improvement System (SSiS-RS) and Social Responsiveness Scale (SRS-2). Secondary outcome measures (i.e. explorative mediators) include social knowledge, social cognition, social anxiety, social contacts and feelings of parenting competency of caregivers. Moreover, demographic and diagnostic measures are assessed as potential moderators of treatment effectiveness. Assessments of adolescents, parents, and teachers take place at baseline (week 0), intermediate (week 7), post intervention (week 14), and at follow-up (week 28). This is the first RCT on the effectiveness of the PEERS® parent-assisted curriculum which includes an active control condition. The outcome of social skills is assessed using observational assessments and multi-informant questionnaires. Additionally, factors related to social learning are assessed at several time points, which will enable us to explore potential mediators and moderators of treatment effect. Dutch trail register NTR6255 (NL6117). Registered February 8th, 2017 - retrospectively registered.


Attenuation of oxidative damage-associated cognitive decline by Withania somnifera in rat model of streptozotocin-induced cognitive impairment.
Oxidative stress is a critical contributing factor to age-related neurodegenerative disorders. Therefore, the inhibition of oxidative damage, responsible for chronic detrimental neurodegeneration, is an important strategy for neuroprotective therapy. Withania somnifera (WS) extract has been reported to have potent antioxidant and free radical quenching properties in various disease conditions. The present study evaluated the hypothesis that WS extract would reduce oxidative stress-associated neurodegeneration after intracerebroventricular injection of streptozotocin (ICV-STZ) in rats. To test this hypothesis, male Wistar rats were pretreated with WS extract at doses of 100, 200, and 300 mg/kg body weight once daily for 3 weeks. On day 22nd, the rats were infused bilaterally with ICV-STZ injection (3 mg/kg body weight) in normal saline while sham group received only saline. Two weeks after the lesioning, STZ-infused rats showed cognitive impairment in the Morris water maze test. The rats were sacrificed after 3 weeks of the lesioning for the estimation of the contents of lipid peroxidation, reduced glutathione, and activities of glutathione reductase, glutathione peroxidase, and catalase. Pretreatment with WS extract attenuated behavioral, biochemical, and histological alterations significantly in dose-dependent manner in the hippocampus and cerebral cortex of ICV-STZ-infused rats. These results suggest that WS affords a beneficial effect on cognitive deficit by ameliorating oxidative damage induced by streptozotocin in a model of cognitive impairment.


Regulation by walnut protein hydrolysate on the components and structural degradation of photoaged skin in SD rats.
Skin photoaging induced by consecutive exposure of skin to ultraviolet radiation is primarily responsible for skin aging and preparation of food-derived ingredients with anti-aging functions has been the hot topic worldwide. Dietary consumption of food supplements has been found to modulate skin functions and can be useful in the prevention of skin aging. To evaluate the effect of walnut protein hydrolysate (WPH) on photoaged skin, Sprague-Dawley rats (SD rats) were orally administered with WPH and then were regularly exposed to ultraviolet radiation (UV-R). After a consecutive UV-R for 18 weeks, the delaying efficiency of WPH against elasticity degradation was examined and the mechanical mechanism was explored subsequently. The contents of hydroxyproline (Hyp) and hyaluronic acid (HA) in the extracellular matrix (ECM) were measured by biochemical reactions and color rendering procedures; the levels of types I and III collagen (Col I and III) and the activity of matrix metalloproteinase-1 (MMP-1) were detected by enzyme-linked immunosorbent assay (ELISA); the protein levels of elastin and fibrillin-1 were examined by western blotting. Moreover, the histological change in the skin structure was illustrated by hematoxylin & eosin (HE) and Masson staining. The results revealed that WPH evidently enhanced the elasticity of photoaged skin and stimulated the biosynthesis of ECM components Col I, Hyp and HA in the dermal layer; meanwhile WPH inhibited the MMP-1 activity, alleviated epidermal hyperplasia, and repaired the damaged skin mechanical structure in a dose-dependent manner. In particular, in comparison with the UV-R group, the WPH group in which WPH was administered at a high-dose level showed significantly improved skin appearance, ECM components and structure (P < 0.05). Taken together, the elasticity improvement caused by WPH against the skin photoaging process can be attributed to the regulation of the metabolism of the components and repair of the damaged mechanical structure of the ECM. This research proved the potential of WPH as a functional ingredient for the development of anti-photoaging foods.


Phloretin suppresses metastasis by targeting protease and inhibits cancer stemness and angiogenesis in human cervical cancer cells.
Phloretin, a dihydrochalcone flavonoid, possesses anti-inflammatory activity and inhibits the growth of various cancers. However, the flavonoid's effect on cervical cancer metastasis and angiogenesis remains unknown. In this study, we provide molecular evidence associated with the antimetastatic and antiangiogenic effects of phloretin. In this study, the anti-invasive effect of phloretin (0-60 μM) in cervical cancer cells was evaluated using the Matrigel invasion assay, gelatin zymography, cell-matrix adhesion assay, wound healing assay, and Western blotting. Antiangiogenic potential of phloretin (0-100 μM) was assessed by the Matrigel tube formation assay. The in vivo antitumor effect of phloretin (10 or 20 mg/kg) was fed by oral gavage and determined using subcutaneous inoculation and tail vein injection in immunodeficient nude mice. Phloretin (60 μM) showed marked suppression of invasion and migration through downregulation of matrix metalloproteinase (MMP)-2, MMP-3, and cathepsin S in human SiHa cervical cancer cells. Phloretin (60 μM) reversed the epithelial-mesenchymal transition induced by transforming growth factor-β1 and downregulated mesenchymal markers, such as fibronectin, vimentin, and RhoA. Phloretin (100 μM) treatment significantly inhibited the aldehyde dehydrogenase 1 activity of SiHa cells, reduced the self-renewal properties and stemness signatures of CD44 and Sox-2 in sphere-forming cervical cancer-derived tumor-initiating cells, and inhibited the invasion, MMP-2 activity, and tube formation capacity of human umbilical vein endothelial cells. The ability of phloretin (20 mg/kg) to suppress lung metastasis and tumor growth in SiHa cells was evidenced by tail vein injection and subcutaneous inoculation in a tumor xenograft model. In summary, the findings indicate that phloretin inhibits the metastatic and angiogenic abilities and cancer stemness of SiHa cells, thereby suggesting that this flavonoid is a promising therapeutic agent for the treatment of human cervical cancer cells.


Differential mitotic responses to microtubule-stabilizing and -destabilizing drugs.
Although microtubule interacting agents inhibit spindle dynamics, thereby leading to a block in mitosis, we report that low concentrations of these drugs result in differential mitotic effects. Microtubule-stabilizing agents including Taxol, epothilone B, and discodermolide produce aneuploid populations of A549 cells in the absence of a mitotic block. Such aneuploid populations are diminished in an epothilone B-resistant cell line. In contrast, microtubule-destabilizing agents like colchicine, nocodazole, and vinblastine are unable to initiate aneuploidy. The aneuploid cells result from aberrant mitosis as multipolar spindles are induced by the stabilizing drugs, but not by destabilizing agents. The results suggest that the mechanism underlying aberrant mitosis may not be the same as that responsible for mitotic block, and that the former determines the sensitivity of cells to Taxol-like drugs.


Foreign body inhalation in children: an update.
Accidental inhalation of both organic and non-organic foreign bodies continues to be a cause of childhood morbidity and mortality, requiring prompt recognition and early treatment to minimize the potentially serious and sometimes fatal consequences. In the past, the majority of data on foreign body injuries in children came from single-centre retrospective studies, covering a range of about 3-10 years. Recently, several review papers have discussed the main clinical aspects, Country-specific experiences have been presented, and systematic collections of foreign bodies have been started. Fully aware of the difficulty in meta-analysing data, in an observational context, the aim of the present report is: an attempt to synthesize the epidemiological data published in the literature presenting the evidence on foreign body distribution in a review of the meta-analyses of papers focusing on European and North-American data; improve our ability to prevent and to treat these complex and high risk situations.


Topological Dissection of the Membrane Transport Protein Mhp1 Derived from Cysteine Accessibility and Mass Spectrometry.
Cys accessibility and quantitative intact mass spectrometry (MS) analyses have been devised to study the topological transitions of Mhp1, the membrane protein for sodium-linked transport of hydantoins from Microbacterium liquefaciens. Mhp1 has been crystallized in three forms (outward-facing open, outward-facing occluded with substrate bound, and inward-facing open). We show that one natural cysteine residue, Cys327, out of three, has an enhanced solvent accessibility in the inward-facing (relative to the outward-facing) form. Reaction of the purified protein, in detergent, with the thiol-reactive N-ethylmalemide (NEM), results in modification of Cys327, suggesting that Mhp1 adopts predominantly inward-facing conformations. Addition of either sodium ions or the substrate 5-benzyl-l-hydantoin (L-BH) does not shift this conformational equilibrium, but systematic co-addition of the two results in an attenuation of labeling, indicating a shift toward outward-facing conformations that can be interpreted using conventional enzyme kinetic analyses. Such measurements can afford the Km for each ligand as well as the stoichiometry of ion-substrate-coupled conformational changes. Mutations that perturb the substrate binding site either result in the protein being unable to adopt outward-facing conformations or in a global destabilization of structure. The methodology combines covalent labeling, mass spectrometry, and kinetic analyses in a straightforward workflow applicable to a range of systems, enabling the interrogation of changes in a protein's conformation required for function at varied concentrations of substrates, and the consequences of mutations on these conformational transitions.


A Graded Approach for Evaluating Health Claims about Plant-Based Food Supplements: Application of a Case Study Methodology.
The implementation of REGULATION (EC) No 1924/2006 has led to the formation of a list of health claims that can be used in food supplements (EU 432/2012). However, such supplements are often composed of plant preparations with claims omitted from this list. The peculiarity of plants is related to their long history of use, that could allow claims based on traditionally recognized health effects. In addition, the scientific literature has been enriched over the years through clinical studies that have assessed the bioavailability and efficacy of bioactive components, and investigated their mechanisms of action. Based on existing recognized models which aim to classify research according to the level of scientific evidence, Synadiet developed a three-grade model (A, B or C) for assessing plants health claims. In this paper, the applicability of the model is illustrated through an example for which a Grade B health claim attesting the possible contribution of red clover isoflavones to the improvement of blood lipid levels in postmenopausal women has been attributed. The model appears able to be easily extrapolated to claims pertaining to other plants. If adopted by consensus at European level, this model could initiate the implementation of a positive list of health claims on plant preparations.


Breaking the silence, dismantling taboos: Latino novels on AIDS.
As AIDS has ravaged the world in the last two decades, literature has played an important role in giving testimony of the epidemic. According to different communities and particular experiences, AIDS literature can offer ways of coping and surviving. In the last few years the U.S. Latino/a population has been highly affected by AIDS. The first genres to register AIDS were poetry and theatre. In this essay I examine how AIDS is represented in the first four Latino novels to deal with the subject matter: Ana Castillo's So Far from God, Daniel Torres's Morirás si da una primavera, Elías Miguel Muñoz's The Greatest Performance, and Jaime Manrique's latin Moon in Manhattan. My critical reading centers on how AIDS constitutes a new articulation of identity, particularly gay and ethnic identity. Most importantly, I propose that these novels contribute to dismantling homophobia and compulsory heterosexuality, deconstructing sexual and cultural taboos, and breaking the silence on AIDS/SIDA.


Disciplinary gender balance, research productivity, and recognition of men and women in academia.
Gender disparities in science have become a salient concern for policy makers and researchers. Previous studies have documented a gender gap in research productivity and recognition in the sciences, and different reasons for this gap have been proposed. In this study, we examine four academic fields with different proportions of men and women in their population. We address the following questions: What is the relationship between the gendered make-up of a field and the productivity and recognition of men and women scientists in that academic field? What is the relationship between the publication patterns of men and women in different academic fields and their productivity and recognition? We find that gendered patterns of productivity and recognition favour men in man-dominated subfields (Mathematical Physics and Software Engineering), while women were more productive and highly cited in one woman-dominated subfield (Nursing), though not in another (Psychology). Nursing, a woman-gendered field, provides an interesting counterpoint to the most usual findings regarding gender disparities in academia. Our findings highlight the need to disaggregate academic fields and to bring to the forefront other disciplines that remain under investigated in analyses of gender gaps to potentially elucidate conflicting findings in the literature.


Towards Intelligent Zone-Based Content Pre-Caching Approach in VANET for Congestion Control.
In vehicular ad hoc networks (VANETs), content pre-caching is a significant technology that improves network performance and lowers network response delay. VANET faces network congestion when multiple requests for the same content are generated. Location-based dependency requirements make the system more congested. Content pre-caching is an existing challenge in VANET; pre-caching involves the content's early delivery to the requested vehicles to avoid network delays and control network congestion. Early content prediction saves vehicles from accidents and road disasters in urban environments. Periodic data dissemination without considering the state of the road and surrounding vehicles are considered in this research. The content available at a specified time poses considerable challenges in VANET for content delivery. To address these challenges, we propose a machine learning-based, zonal/context-aware-equipped content pre-caching strategy in this research. The proposed model improves content placement and content management in the pre-caching mode for VANET. Content caching is achieved through machine learning, which significantly improves content prediction by pre-caching the content early to the desired vehicles that are part of the zone. In this paper, three algorithms are presented, the first is zone selection using the customized algorithm, the second is the content dissemination algorithm, and the third is the content pre-caching decision algorithm using supervised machine learning that improves the early content prediction accuracy by 99.6%. The cache hit ratio for the proposed technique improves by 13% from the previous techniques. The prediction accuracy of the proposed technique is compared with CCMP, MLCP, and PCZS+PCNS on the number of vehicles from 10 to 150, with an improved average of 16%. Finally, the average delay reduces over time compared with the state-of-the-art techniques of RPSS, MLCP, CCMP, and PCZS+PCNS. Finally, the average delay shows that the proposed method effectively reduces the delay when the number of nodes increases. The proposed solution improves the content delivery request while comparing it with existing techniques. The results show improved pre-caching in VANET to avoid network congestion.


Analytical vectorial structure of Laguerre-Gaussian beam in the far field.
Based on the vector angular spectrum of the electromagnetic beam and the method of stationary phase, the analytical vectorial structure of the Laguerre-Gaussian beam has been presented in the far field. According to the analytical electromagnetic representations of the TE and TM terms, the energy flux distributions of the TE term, the TM term, and the whole beam are investigated in the far field, respectively. The formulas obtained are applicable not only to the paraxial case, but also to the nonparaxial case. The physical pictures of Laguerre-Gaussian beams are well illustrated from the vectorial structure, which may provide a new approach to manipulate laser beams.


Intramedullary Compression Screw Fixation of Proximal Phalangeal Fractures: A Systematic Literature Review.
Proximal phalangeal fractures have traditionally been fixed via either Kirschner wires or dorsal plating. Concerns regarding lack of compression and potential for infection with wire fixation, and adhesion formation and stiffness with plating, have lead to alternative fixation methods, such as intramedullary screw fixation. However, the literature regarding this modality is limited. Methods: A systematic review was performed to review the literature regarding intramedullary screw fixation for proximal phalangeal fractures. English language studies that reported original data and commented on at least one postoperative measure of function were eligible for inclusion. 4 studies were eligible for inclusion, with a further 3 studies assessing proximal and middle phalanges analysed separately. Total active motion was greater than 240° in all proximal phalangeal studies; mean post-operative DASH was 3.62. 6% of patients sustained a major complication. Intramedullary screw fixation of proximal phalangeal fractures is safe, providing stable fixation to allow early motion.


Correlates of hepatitis C virus infection among incarcerated Ghanaians: a national multicentre study.
A national multicentre cross-sectional study was undertaken on the correlates of hepatitis C virus (HCV) infection in a sample of inmates from eight Ghanaian prisons. A total of 1366 inmates from eight of the ten regional central prisons in Ghana were enrolled between May 2004 and December 2005. Subjects voluntarily completed a risk-factor questionnaire and provided blood specimens for unlinked anonymous testing for the presence of antibodies to HCV. These data were analysed using both univariate and multivariate techniques. The median age of participants was 36.5 years (range 16-84 years). Of the 1366 inmates tested, HCV seroprevalence was 18.7%. On multivariate analysis, the independent determinants of HCV infection were being incarcerated for longer than the median time served of 36 months [odds ratio (OR) 5.8; 95% confidence interval (95% CI) 5.0-6.9], history of intravenous drug use (OR 4.5; 95% CI 3.8-5.4) and homosexuality (OR 3.1; 95% CI 2.5-3.9). Consistent with similar studies worldwide, the prevalence of HCV in prison inmates was higher than the general population in Ghana, suggesting probable transmission in prisons in Ghana through intravenous drug use and unsafe sexual behaviour.


Studies on mode of action of vitamin A.
Effect of feeding 5000,10 000, 20 000, 30 000 and 40 000 I.U. of vitamin A for two days to 25 days old rats has been studied on liver protein, RNA and DNA, liver and plasma lipids and adrenal cholesterol. The incorporation of palmitate- I-14-C into liver and plasma lipids has been studied in vitamin A fed rats. Two patterns of effects of vitamin A were observed in rats on their liver protein, RNA and DNA and liver and plasma lipids. At lower amounts of vitamin A feeding either the above did not change or were increased, but at higher amounts of vitamin A feeding the above were decreased as compared to the controls. Plasma nonesterified fatty acids were increased and adrenal cholesterol decreased in rats fed 5000 I.U. of vitamin A, but were not affected in rats fed higher amounts of vitamin A. The utilization of palmitate-I-14-C for the synthesis of liver triglycerides and phosphoglycerides was reduced in rats fed higher amounts of vitamin A, but was not significantly different from the controls in rats fed liver amounts of vitamin A. The effects of vitamin A are influenced by the age of the animal as well as the amounts of vitamin A fed. The results show that the effects of vitamin A are exerted by the stimulation of adrenal activity (increased corticoid synthesis).


Dietary structured triacylglycerols containing docosahexaenoic acid given from birth affect visual and auditory performance and tissue fatty acid profiles of rats.
To examine whether it is possible to enhance the level of 22:6(n-3) in the central nervous system, newborn rats were fed dietary supplements containing oils with either specific or random triacylglycerol structure, but similar concentrations of polyunsaturated fatty acids. In the specific structured oil, 22:6(n-3) was located in the sn-2 position, whereas it was equally distributed among the three positions in the triacylglycerol molecule in the randomized oil. A reference group was fed rat milk before weaning and nonpurified diet after weaning. After 12 wk, the levels of 22:6(n-3) in brain and liver phospholipids were higher in the groups fed the experimental diets than in the reference group. The specific structured oil resulted in the highest level of 22:6(n-3) in the brain, whereas the level of 22:6(n-3) was highest in the liver of the group fed randomized oil, indicating differences in metabolism of fatty acids resulting from their position in the dietary triacylglycerol molecule. The higher levels of 22:6(n-3) were accompanied by significantly lower levels of the long-chain (n-6) polyunsaturated fatty acids compared with the reference group. The fatty acid profiles, including the level of 22:6(n-3), in the retina phospholipids were not affected by the three different diets apart from a lower level of 20:4(n-6) in rats fed the experimental diets, indicating a strong tendency to maintain a high level of 22:6(n-3) in the retina. The changes in the fatty acid profiles did not result in differences in learning ability, but caused changes in visual function, evidenced by higher latency of the b-wave and lower oscillatory potential, and in auditory brainstem response, evidenced by generally greater amplitude of wave Ia in the group fed specific structured oil.


Arterial supply of the posterior interventricular sulcus: a CT coronary angiographic study.
The objective of this study was to determine the different vascularization patterns of the posterior interventricular sulcus (PIS) with coronary CT angiography. Three hundred and fifty-six coronary CT angiograms (CCTA) were retrospectively analyzed in 248 men and 108 women (mean age, 54.9 years ± 13.6 [standard deviation]). The PIS was divided into three segments from the crux cordis to the notch of the cardiac apex according to the American Heart Association classification (basal, mid ventricular and apical), and the artery or arteries supplying each segment were recorded. The relative frequency of the different vascularization patterns was calculated and the distribution of dominance types was recorded. Blood was supplied to the PIS by one or more branches of the right coronary artery (RCA), the left circumflex artery (LCX), or the left anterior descending artery (LAD). We observed 25 different irrigation patterns. In the most frequent pattern (31.3%), the basal and mid-ventricular segments were perfused by a single arterial branch originating from the RCA at the crux, and the apical segment was perfused by the LAD traveling beyond the notch of the cardiac apex and entering the posterior interventricular sulcus. Of the 356 cases, the circulation was right dominant in 310 (87.1%), left dominant in 34 (9.5%), and balanced in 12 (3.4%) cases. Individual segments were perfused by a single artery in 288 (80.9%) cases, and by more than one in the remainder. CCTA allows detailed assessment of the arterial supply of the PIS, and allowed to describe 25 subtypes. This information is of potential value to both cardiac surgeons and interventional cardiologists who plan bypass surgery or angioplasty aiming at the posterior interventricular artery.


Effects of interval training on inflammatory biomarkers in patients with ischemic heart failure.
Objectives. Exercise training has been proposed to have anti-inflammatory effects. We examined whether aerobic interval training (AIT) can attenuate the inflammatory response in ischemic heart failure (HF) as measured by serum biomarkers representing a broad spectrum of activated inflammatory pathways. Design. We conducted a controlled prospective trial recruiting 30 patients (19 in the AIT group and 11 in the control group) with ischemic HF and an implantable cardioverter defibrillator (ICD). This study is a sub study of the previously reported "Aerobic interval training in patients with heart failure and an ICD" (Eur J Prev Cardiol. 22 March 2015; 22:296-303). Patients in the AIT group exercised for 12-weeks completing a total of 36 AIT sessions. We analyzed serum levels of C-reactive protein, pentraxin-3, osteoprotegerin, brain natriuretic peptide, neopterin, and soluble tumor necrois factor type 1 and 2, all known to predict an adverse outcome in HF, at baseline and following the 12-week AIT intervention. Results. The AIT group significantly increased peak oxygen uptake and improved endothelial function compared to the sedentary control group. No statistically significant changes in serum levels of the biomarkers were detected from baseline following the AIT intervention and, there were no significant differences in changes of these mediators between the AIT and the control group. Conclusions. A 12-week AIT intervention, although improving exercise capacity and endothelial function, did not attenuate serum inflammatory biomarkers in stable ischemic HF patients with an ICD on optimal medical therapy.


Synthetic absorbable and nonabsorbable microsutures: a histological comparison.
The increasing usage of microsurgery in gynaecology and the recent release of a synthetic absorbable microsuture prompted a comparative study between this material and a nonabsorbable microsuture. Ethilon and Coated Vicryl sutures (Ethicon Inc.) were inserted into rabbit uteri and the histological response compared at 35 and 70 days using both light and polarizing microscopy. The results indicated that although the predominating cell types differed, the overall histological sequelae were markedly less with the synthetic absorbable suture than with the nonabsorbable suture materials.


Mycobacterium tuberculosis controls microRNA-99b (miR-99b) expression in infected murine dendritic cells to modulate host immunity.
Mycobacterium tuberculosis resides and replicates within host phagocytes by modulating host microbicidal responses. In addition, it suppresses the production of host protective cytokines to prevent activation of and antigen presentation by M. tuberculosis-infected cells, causing dysregulation of host protective adaptive immune responses. Many cytokines are regulated by microRNAs (miRNAs), a newly discovered class of small noncoding RNAs, which have been implicated in modulating host immune responses in many bacterial and viral diseases. Here, we show that miRNA-99b (miR-99b), an orphan miRNA, plays a key role in the pathogenesis of M. tuberculosis infection. We found that miR-99b expression was highly up-regulated in M. tuberculosis strain H37Rv-infected dendritic cells (DCs) and macrophages. Blockade of miR-99b expression by antagomirs resulted in significantly reduced bacterial growth in DCs. Interestingly, knockdown of miR-99b in DCs significantly up-regulated proinflammatory cytokines such as IL-6, IL-12, and IL-1β. Furthermore, mRNA and membrane-bound protein data indicated that inhibition of miR-99b augments TNF-α and TNFRSF-4 production. Thus, miR-99b targets TNF-α and TNFRSF-4 receptor genes. Treatment of anti-miR-99b-transfected DCs with anti-TNF-α antibody resulted in increased bacterial burden. Thus, our findings unveil a novel host evasion mechanism adopted by M. tuberculosis via miR-99b, which may open up new avenues for designing miRNA-based vaccines and therapies.


Psychosine enhances the shedding of membrane microvesicles: Implications in demyelination in Krabbe's disease.
In prior studies, our laboratory showed that psychosine accumulates and disrupts lipid rafts in brain membranes of Krabbe's disease. A model of lipid raft disruption helped explaining psychosine's effects on several signaling pathways important for oligodendrocyte survival and differentiation but provided more limited insight in how this sphingolipid caused demyelination. Here, we have studied how this cationic inverted coned lipid affects the fluidity, stability and structure of myelin and plasma membranes. Using a combination of cutting-edge imaging techniques in non-myelinating (red blood cell), and myelinating (oligodendrocyte) cell models, we show that psychosine is sufficient to disrupt sphingomyelin-enriched domains, increases the rigidity of localized areas in the plasma membrane, and promotes the shedding of membranous microvesicles. The same physicochemical and structural changes were measured in myelin membranes purified from the mutant mouse Twitcher, a model for Krabbe's disease. Areas of higher rigidity were measured in Twitcher myelin and correlated with higher levels of psychosine and of myelin microvesiculation. These results expand our previous analyses and support, for the first time a pathogenic mechanism where psychosine's toxicity in Krabbe disease involves deregulation of cell signaling not only by disruption of membrane rafts, but also by direct local destabilization and fragmentation of the membrane through microvesiculation. This model of membrane disruption may be fundamental to introduce focal weak points in the myelin sheath, and consequent diffuse demyelination in this leukodystrophy, with possible commonality to other demyelinating disorders.


Expression profiling of serum inducible genes identifies a subset of SRF target genes that are MKL dependent.
Serum Response Factor (SRF) is a transcription factor that is required for the expression of many genes including immediate early genes, cytoskeletal genes, and muscle-specific genes. SRF is activated in response to extra-cellular signals by its association with a diverse set of co-activators in different cell types. In the case of the ubiquitously expressed immediate early genes, the two sets of SRF binding proteins that regulate its activity are the TCF family of proteins that include Elk1, SAP1 and SAP2 and the myocardin-related MKL family of proteins that include MKL1 and MKL2 (also known as MAL, MRTF-A and -B and BSAC). In response to serum or growth factors these two classes of co-activators are activated by different upstream signal transduction pathways. However, it is not clear how they differentially activate SRF target genes. In order to identify the serum-inducible SRF target genes that are specifically dependent on the MKL pathway, we have performed microarray experiments using a cell line that expresses dominant negative MKL1. This approach was used to identify SRF target genes whose activation is MKL-dependent. Twenty-eight of 150 serum-inducible genes were found to be MKL-dependent. The promoters of the serum-inducible genes were analyzed for SRF binding sites and other common regulatory elements. Putative SRF binding sites were found at a higher rate than in a mouse promoter database but were only identified in 12% of the serum-inducible promoters analyzed. Additional partial matches to the consensus SRF binding site were found at a higher than expected rate in the MKL-dependent gene promoters. The analysis for other common regulatory elements is discussed. These results suggest that a subset of immediate early and SRF target genes are activated by the Rho-MKL pathway. MKL may also contribute to the induction of other SRF target genes however its role is not essential, possibly due to other activation mechanisms such as MAPK phosphorylation of TCFs.


Bleeding in anticoagulated patients with atrial fibrillation: practical considerations.
Major bleeding (especially intracranial hemorrhage) is the most feared adverse event observed in patients with atrial fibrillation (AF) receiving oral anticoagulation. Clinical risk factor-based scores have modest ability to predict major or clinically relevant bleeds, and blood biomarkers are increasingly implemented to improve bleeding prognostication in patients with AF on life‑long anticoagulation. To improve the safety of anticoagulation in the era of non-vitamin K antagonist oral anticoagulants (NOACs, or direct oral anticoagulants [DOACs], including dabigatran, rivaroxaban, apixaban, and edoxaban), specific demographic, clinical, and laboratory variables should be considered. The current review summarizes practical challenges in the management of oral anticoagulation with emphasis on the risk assessment tools, elderly or underweight patients, cancer patients, impact of chronic kidney disease, liver cirrhosis, and thrombocytopenia in the context of bleeding risk in patients with AF.


Single-cell RNA sequencing reveals a signature of sexual commitment in malaria parasites.
Pathogens have to balance transmission with persistence. For Plasmodium falciparum, the most widespread and virulent malaria parasite, persistence within its human host requires continuous asexual replication within red blood cells, while its mosquito-borne transmission depends on intra-erythrocytic differentiation into non-replicating sexual stages called gametocytes. Commitment to either fate is determined during the preceding cell cycle that begins with invasion by a single, asexually committed merozoite and ends, 48 hours later, with a schizont releasing newly formed merozoites, all committed to either continued asexual replication or differentiation into gametocytes. Sexual commitment requires the transcriptional activation of ap2-g (PF3D7_1222600), the master regulator of sexual development, from an epigenetically silenced state during asexual replication. AP2-G expression during this 'commitment cycle' prepares gene expression in nascent merozoites to initiate sexual development through a hitherto unknown mechanism. To maintain a persistent infection, the expression of ap2-g is limited to a sub-population of parasites (1-30%, depending on genetic background and growth conditions). As sexually committed schizonts comprise only a sub-population and are morphologically indistinguishable from their asexually committed counterparts, defining their characteristic gene expression has been difficult using traditional, bulk transcriptome profiling. Here we use highly parallel, single-cell RNA sequencing of malaria cultures undergoing sexual commitment to determine the transcriptional changes induced by AP2-G within this sub-population. By analysing more than 18,000 single parasite transcriptomes from a conditional AP2-G knockdown line and NF54 wild-type parasites at multiple stages of development, we show that sexually committed, AP2-G+ mature schizonts specifically upregulate additional regulators of gene expression, including other AP2 transcription factors, histone-modifying enzymes, and regulators of nucleosome positioning. These epigenetic regulators may act to facilitate the expression and/or repression of genes that are necessary for the initiation of gametocyte development in the subsequent cell cycle.


Studies on synthesis and degradation rates and some molecular properties of guinea-pig muscle acylphosphatase.
Acylphosphatase (acylphosphate phosphohydrolase, EC 22.214.171.124) was purified from guinea-pig muscle by a procedure involving immuno-affinity chromatography and a subsequent ion-exchange chromatography. This purification technique gave an overall yield of about 60% and permitted the isolation of three molecular forms with acylphosphatase activity, with a distribution greatly resembling those found in horse and turkey muscle. The main form appears to be very similar to the corresponding form in horse and turkey muscle, as indicated by amino acid composition, end-group analysis, the presence of glutathione as a mixed disulphide in almost the same stoichiometric ratio and kinetic analysis. From turnover data, the main form of acylphosphatase in guinea-pig muscle exhibits a degradation constant of 0.10 day-1, corresponding to a half-life of 6.8 days. These values are very close to those found for muscle total soluble proteins.


Age-dependent changes in material properties of the brain and braincase of the rat.
Clinical and biomechanical evidence indicates that mechanisms and pathology of head injury in infants and young children may be different from those in adults. Biomechanical computer-based modeling, which can be used to provide insight into the thresholds for traumatic tissue injury, requires data on material properties of the brain, skull, and sutures that are specific for the pediatric population. In this study, brain material properties were determined for rats at postnatal days (PND) 13, 17, 43, and 90, and skull/suture composite (braincase) properties were determined at PND 13, 17, and 43. Controlled 1 mm indentation of a force probe into the brain was used to measure naive, non-preconditioned (NPC) and preconditioned (PC) instantaneous (G(i)) and long-term (G( infinity )) shear moduli of brain tissue both in situ and in vitro. Brains at 13 and 17 PND exhibited statistically indistinguishable shear moduli, as did brains at 43 and 90 PND. However, the immature (average of 13 and 17 PND) rat brain (G(i) = 3336 Pa NPC, 1754 Pa PC; G( infinity )= 786 Pa NPC, 626 Pa PC) was significantly stiffer (p < 0.05) than the mature (average of 43 and 90 PND) brains (G(i) = 1721 Pa NPC, 1232 Pa PC; G( infinity ) = 508 Pa NPC, 398 Pa PC). A "reverse engineering" finite element model approach, which simulated the indentation of the force probe into the intact braincase, was used to estimate the effective elastic moduli of the braincase. Although the skull of older rats was significantly thicker than that of the younger rats, there was no significant age-dependent change in the effective elastic modulus of the braincase (average value = 6.3 MPa). Thus, the increase in structural rigidity of the braincase with age (up to 43 PND) was due to an increase in skull thickness rather than stiffening of the tissue. These observations of a stiffer brain and more compliant braincase in the immature rat compared with the adult rat will aid in the development of age-specific experimental models and in computational head injury simulations. Specifically, these results will assist in the selection of forces to induce comparable mechanical stresses, strains and consequent injury profiles in brain tissues of immature and adult animals.


What's cooking, if not meat? Effects of repeated home-use, recipe inspiration and meal context on perception of plant-based meat analogues.
Plant-based meat analogues (PBMA) may help consumers in shifting towards more plant-based diets, but PBMA are not widely used yet, and little is known about their longer-term acceptance. This study investigated whether consumer acceptance of PBMA changed with repeated home-use, and whether providing recipe suggestions in the form of meal boxes could influence PBMA acceptance. To this end, Dutch regular meat eaters (n = 61) prepared, consumed and evaluated two meals (one from a meal box, one self-created) with PBMA (PB mince and PB chicken, counterbalanced across meal types) per week at home for four weeks. As a secondary objective, potential longer-term effects of repeated home-use of PBMA on meat (analogue) consumption habits and attitudes (e.g. motives for choosing PBMA, attitudes toward eating less meat) were assessed in a pre-vs post-intervention survey. Responses were compared with a control group of consumers not participating in the home-use study (n = 179). Results provided no evidence that PBMA liking changed with repeated home-use, nor that the provision of meal boxes increased liking of PBMA. Instead, PBMA liking was strongly influenced by the meal context, which may have overruled potential effects of repeated exposure. Findings from the pre- vs. post-intervention survey suggest that repeated exposure may stimulate longer-term consumption of PBMA, although more seems needed to bring about a structural shift toward a less animal-based consumption pattern. Future research should investigate whether more sophisticated recipes that provide a suitable meal context for PBMA and elevate consumers' meal experiences may improve PBMA acceptance and facilitate the transition toward more sustainable diets.


Characteristics of solubilized human-somatotropin-binding protein from the liver of pregnant rabbits.
A specific binding site for somatotropin was solubilized by 1% (v/v) Triton X-100 from a crude particulate membrane fraction of pregnant rabbit liver, partially purified and characterized. The solubilized binding site retained many of the characteristics observed in the original particulate fraction, indicating that extraction of the binding site with Triton X-100 does not cause any major changes in its properties. The binding of human 125I-labelled-somatotropin to the solubilized binding site is a saturable and reversible process, depending on temperature, incubation time, pH and ionic environment. Analysis of the kinetic data revealed a finite number of binding sites with an affinity constant of 0.32 x 10(10)M-1. The binding activity for human 125I-labelled-somatotropin was adsorbed to a concanavalin-A-Sepharose column and was dissociated from the column with alpha-methyl-D-glucoside, suggesting that the binding protein may be a glycoprotein. Using affinity chromatography on concanavalin-A-Sepharose, ion-exchange chromatography on DEAE-cellulose and gel filtration on Sepharose 6B, the binding protein was purified 1000-4000-fold from the original liver homogenate. When the partially purified preparation was chromatographed on Sepharose 6B, the binding protein eluted as a molecule with an apparent molecular weight of 200000, with a Stokes' radius of 4.9 nm. Sucrose-density-gradient centrifugation of the preparation showed that the sedimentation coefficient of the binding protein was 7.2S. Isoelectric focusing experiments revealed that a major part of the protein has an acidic pI (4.2-4.5). Exposure of the protein to trypsin decreased the binding activity for human 125I-labelled-somatotropin or bovine 125I-labelled-somatotropin, whereas ribonuclease, deoxyribonuclease, phospholipase C or neuraminidase had little or no effect.


A study on the nutrient foramina of adult humerii.
It is not uncommon to see the non union of the fractures in the long bones. Among the various reasons for the nonunion of the fractured bones, the nutrient artery plays an important role. This study was aimed at analyzing the nutrient foramina in dry adult humerii ,with regards to the number, size and the location of the nutrient foramen with respect to the surfaces and the zones and its distance from the mid point of the humerus. This was an analytical study. All the humerii from various medical colleges of the Vinayaka Missions University in Salem were included in the study. Those which were damaged and those which had pathological abnormalities were excluded. The following parameters were noted; namely, the length of the humerus, the number and the size of the nutrient foramen and the location of the nutrient foramen with respect to the surfaces and the zones of the humerus and its distance from the mid-point of the humerus were analyzed. The length of the humerus and the mid point of the humerus were measured by using the osteometric board, whereas the size of the nutrient foramen was measured by using various size of hypodermic needles. When more than one foramen was found, the larger one was taken as the dominant foramen and its size was measured. All the data were noted and the statistical analysis was done by calculating the mean, the range and the standard deviation. Totally, 258 adult dry humerii were studied. The mean length of the humerii was 27.96 cm, with a SD of 2.18. The mean size of the nutrient foramen was 0.828 mm, with a SD of 0.26. The mean distance of th dominant nutrient foramen from the mid point of the humerus was 2.31 cm, with a SD of 1.25 cm. In majority of the humerii (86.43%), the nutrient foramen was located in the middle 1/3(rd) of the bone and in 13.57% of the bones, it was located in the lower 1/3(rd) of the bone. The location of the nutrient foramen in the anteromedial surface was 89.92%, that in the posterior surface was 8.53% and that in the anterolateral surface was 1.55%.


A quantitative ethogram of aggressive and submissive behaviors in recently regrouped pigs.
Twenty prepubertal Yorkshire X Hampshire pigs were mixed in groups of four. Their behaviors were recorded on video tape for 48 h, and a detailed behavioral analysis was performed. Aggressive interactions of 10 unique pairs of pigs were observed. Twenty-five distinct behavioral categories were identified in the total data set, which contained 1,846 behaviors. On average, an interacting pair showed 92 behavioral elements (range: 10 to 307). Eighty-one percent of the behaviors observed consisted of bites and pushes given and received. Bites were targeted mainly at the ears (55%), face (17%) and neck (23%). Most bites to the rump and turning the body 180 degrees occurred during the last third of the fight. Pigs that eventually won fights showed higher incidences of ear bites and lower incidences than expected of head-under-head pushing and body-turning. Pigs that lost fights showed higher frequencies of head-under-head pushing and body-turning. Losers also showed a lower frequency of rump biting. Overall, many of the behaviors performed by the losing pigs were followed by the loser receiving an ear bite. Body-turning was a sign of submission and was always preceded by, and often followed, ear-biting. Once a pig showed body-turning, it generally avoided further face-to-face interaction. Behaviors exhibited as signs of submission were found in each of the 10 pairs observed.


Linked opening angle and histological and mechanical aspects of the proximal pulmonary arteries of healthy and pulmonary hypertensive rats and calves.
Understanding how arterial remodeling changes the mechanical behavior of pulmonary arteries (PAs) is important to the evaluation of pulmonary vascular function. Early and current efforts have focused on the arteries' histological changes, their mechanical properties under in vitro mechanical testing, and their zero-stress and no-load states. However, the linkage between the histology and mechanical behavior is still not well understood. To explore this linkage, we investigated the geometry, residual stretch, and histology of proximal PAs in both adult rat and neonatal calf hypoxic models of pulmonary hypertension (PH), compared their changes due to chronic hypoxia across species, and proposed a two-layer mechanical model of artery to relate the opening angle to the stiffness ratio of the PA outer to inner layer. We found that the proximal PA remodeling in calves was quite different from that in rats. In rats, the arterial wall thickness, inner diameter, and outer layer thickness fraction all increased dramatically in PH and the opening angle decreased significantly, whereas in calves, only the arterial wall thickness increased in PH. The proposed model predicted that the stiffness ratio of the calf proximal PAs changed very little from control to hypertensive group, while the decrease of opening angle in rat proximal PAs in response to chronic hypoxia was approximately linear to the increase of the stiffness ratio. We conclude that the arterial remodeling in rat and calf proximal PAs is different and the change of opening angle can be linked to the change of the arterial histological structure and mechanics.


Current practice in diagnosis and treatment of breast cancer in Cheicko Balbala Hospital Djibouti.
This report details the results of the first breast cancer (BC) prevalence study done in Djibouti, a small country in the Horn of Africa. The study was done in the Surgical Department of Balbala Hospital (also known as the Italian Hospital). 102 female patients with clinical BC were evaluated between 2012 and 2017. All patients came directly to the hospital without a prior referral. Fine Needle Aspiration (FNA) was carried out on all suspected lesions representing 40.6 % of patients. A biopsy was carried out on all clinically evident lesions. Following histopathological confirmation for all patients, 86 women (84,31%) accepted surgical procedure and clinico-histopathological staging was possible. 16 (15.69%) women refused surgery. There are no radiotherapy and chemotherapy facilities in Djibouti however hormonal therapy, Tamoxifen, is available. The Italian Government built the Hospital in 1985 in Balbala, a District of Djibouti Ville ,with a population of over 250.000. It is an example of a successful cooperation between Italy and Djibouti in the health sector. Following a long period of assistance and support from the Italian Ministry of Foreign Affairs, the Hospital is now taken completely managed by the Ministry of Health of Djibouti . The hospital is one of the main referral hospitals in the country. Better provision of information to the local population and medical general practitioner about breast cancer would improve diagnosis, the treatment and the overall prognosis of this disease. Breast Cancer, Epidemiology, Surgery, Italian Balbala Hospital Djibouti.


The latex serologic test for syphilis-a new screening procedure.
A new macroscopic screening test for syphilis, the Latex-sts test, is extraordinarily simple. After inactivation of the patient's serum for 30 minutes at 56 degrees C the test is performed by mixing the patient's serum with latex particles coated with cardiolipin and a protein fraction obtained from the non-pathogenic Reiter strain of Treponema pallidum. Two to three minutes after mixing, the result of the test is observed on a ringed serologic plate. The sensitivity, specificity and reproducibility of the new test are equivalent to those of the qualitative Venereal Disease Research Laboratory tube test. The advantages of the Latex-sts are that it can be done in a short time, it is simple and it requires a minimum of laboratory equipment. The coated latex particles are stable for 12 months.


Providers' perceptions of disrespect and abuse during childbirth: a mixed-methods study in Kenya.
Disrespect and abuse during childbirth are violations of women's human rights and an indicator of poor-quality care. Disrespect and abuse during childbirth are widespread, yet data on providers' perspectives on the topic are limited. We examined providers' perspectives on the frequency and drivers of disrespect and abuse during facility-based childbirth in a rural county in Kenya. We used data from a mixed-methods study in a rural county in Western Kenya with 49 maternity providers (32 clinical and 17 non-clinical) in 2016. Providers were asked structured questions on disrespect and abuse, followed by open-ended questions on why certain behaviours were exhibited (or not). Most providers reported that women were often treated with dignity and respect. However, 53% of providers reported ever observing other providers verbally abuse women and 45% reported doing so themselves. Observation of physical abuse was reported by 37% of providers while 35% reported doing so themselves. Drivers of disrespect and abuse included perceptions of women being difficult, stress and burnout, facility culture and lack of accountability, poor facility infrastructure and lack of medicines and supplies, and provider attitudes. Provider bias, training and women's empowerment influenced how different women were treated. We conclude that disrespect and abuse are driven by difficult situations in a health system coupled with a facilitating sociocultural environment. Providers resorted to disrespect and abuse as a means of gaining compliance when they were stressed and feeling helpless. Interventions to address disrespect and abuse need to tackle the multiplicity of contributing factors. These should include empowering providers to deal with difficult situations, develop positive coping mechanisms for stress and address their biases. We also need to change the culture in facilities and strengthen the health systems to address the system-level stressors.


Chemical Ecogenomics-Guided Discovery of Phytotoxic α-Pyrones from the Fungal Wheat Pathogen Parastagonospora nodorum.
A biosynthetic gene cluster that is significantly upregulated in the fungal wheat pathogen Parastagonospora nodorum during plant infection was reconstructed heterologously in Aspergillus nidulans. This led to the discovery of five new α-pyrone polyketides, alternapyrones B-F (2-6). Compounds 5 and 6, which contain a highly substituted dihydrofuran, exhibited phytotoxicity on wheat seed germination. It is demonstrated that only three enzymes, one highly reducing polyketide synthase and two multifunctional P450 oxygenases, are needed to synthesize the structurally complex products.


[Nitric oxide synthesis during long-term adaptation to intensive muscular work in female sportsmen].
14 trained and 21 non-trained girls 18-22 years of age have been inspected. We found that systematically trained girls had a higher level of nitric oxide synthesis through calcium-dependent L-arginine oxidation by constitutive NO-synthase isoforms (eNOS, nNOS) and through reduction of stable oxidized NO metabolites. NO synthesized de novo in calcium-dependent pathway provides a long-term organism adaptation to physical loads of high volume and intensity at the beginning and in the middle of stress-aggravated competition period. At the end of competition period we detected significant activation of inducible calcium-independent de novo NO synthesis from L-arginine.


Regulation of the yeast CYT1 gene encoding cytochrome c1 by HAP1 and HAP2/3/4.
Mitochondrial biogenesis requires the coordinate induction of hundreds of genes that reside in the nucleus. We describe here a study of the regulation of the nuclear-encoded cytochrome c1 of the b-c1 complex. Unlike cytochrome c, which is encoded by two genes, CYC1 and CYC7, c1 is encoded by a single gene, CYT1. The regulatory region of the CYT1 promoter contains binding sites for the HAP1 and HAP2/3/4 transactivators that regulate CYC1. The binding of HAP1 to the CYT1 element was studied in detail and found to differ in two important respects from binding to the CYC1 element. First, while CYC1 contains two sites that bind HAP1 cooperatively, CYT1 has a single high-affinity site. Second, while the CYT1 site and the stronger HAP1-binding site of CYC1 share a large block of homology, the HAP1 footprints at these sites are offset by several nucleotides. We discuss how these differences in HAP1 binding might relate to the difference in the biology of cytochrome c and cytochrome c1.


Combined obturator and palatal-lift prosthesis: a case report.
A technique for the fabrication of a combined obturator and palatal-lift prosthesis is presented. The metal framework embodied the principles of partial denture design. A sequence of steps was used to achieve an accurate representation of the pharyngeal tissues, on which the pharyngeal extension was constructed. This extension was fabricated in an autopolymerizing acrylic resin to avoid lengthy laboratory procedures.


Molecular endocrinology and physiology of the aging central nervous system.
Aging is associated with a progressive decline in physical and cognitive functions. The impact of age-dependent endocrine changes regulated by the central nervous system on the dynamics of neuronal behavior, neurodegeneration, cognition, biological rhythms, sexual behavior, and metabolism are reviewed. We also briefly review how functional deficits associated with increases in glucocorticoids and cytokines and declining production of sex steroids, GH, and IGF are likely exacerbated by age-dependent molecular misreading and alterations in components of signal transduction pathways and transcription factors.


Functional and Structural Longitudinal Change Patterns in Adolescent Brain.
Functional magnetic resonance imaging (fMRI) and structural magnetic resonance imaging (sMRI) are two widely used techniques to analyze longitudinal brain functional and structural change in adolescents. Although longitudinal changes in intrinsic functional and structural changes have been studied separately, most studies focus on univariate change rather than estimating multivariate patterns of functional network connectivity (FNC) and gray matter (GM) changes with increased age. To analyze whole-brain structural and functional changes with increased age, we suggest two complementary techniques (1: linking of functional change pattern (FCP) to voxel-wise ∆GM and 2: the connection between FCP and structural change pattern (SCP)). In this study, we apply our approaches to the functional and GM data from the large-scale Adolescent Brain and Cognitive Development (ABCD) data. We find a significant correlation between FCP and voxel-wise ∆GM for two components. We also investigate the links between FCP and SCP and hypothesize that functional connectivity and GM continue to exhibit linked changes during adolescence.Clinical Relevance- This work captures the whole-brain functional and structural change patterns link by introducing two complementary techniques.


Evaluation of the quality of life of children with celiac disease and their parents: a case-control study.
The purpose of the present study was to evaluate the quality of life (QoL) of children with CD and of their parents and to compare it with that of children without CD and of their parents. A case-control study was conducted to evaluate the quality of life of children (5-12 years) with CD and one of their parents, compared to the QoL of children without CD (and their parents as their caregivers ). The QoL was assessed by applying the following questionnaires: AUQUEI (children) and WHOQOL-BREF (parents). QoL was evaluated in 33 children with CD, 63 children without CD, and of their respective parents as their parent caregivers (96 adults). QoL total scores were similar between the groups of children with and without CD. However, in the Leisure dimension, the scores of children with CD were significantly lower than those of the controls (P = 0.029). Similarly, when assessing the QoL of the parents, we found scores significantly lower in the social dimension (P = 0.0196) for parents of children with CD compared to parents of children without CD. Family income presented an impact on the QoL in adults, but did not affect children. In CD group, children of mothers who had lower educational levels presented better scores in the function dimension, regarding self-care and autonomy. There is an impairment of the QoL of children with CD and of their parents, with regard to social life, particularly in the leisure (children) and social (adults) dimensions.


Heartfelt images: learning cardiac science artistically.
There are limited curricular options for medical students to engage in art-making during their training. Yet, it is known that art-making confers a variety of benefits related to learning. This qualitative study utilises a visual methodology to explore students' art-making in the context of the cardiovascular sciences. The existence of a multiyear repository of medical/dental student generated, cardiac-inspired art, collected over 6 years, provided the opportunity to explore the nature of the art made. The aim was to categorise the art produced, as well as the depth and breadth of understanding required to produce the art. The data set included a wide variety of titled art (paintings, photographs, sketches, sculptures, collages, poetry and music/dance). Systematic curation of the collection, across all media, yielded three main categories: anatomical renderings, physiology/pathophysiology renderings and kinesthetic creations (music/dance/tactile). Overall (medical and dental) student-generated art suggested a high level of content/process understanding, as illustrated by attention to scientific detail, integration of form and function as well as the sophisticated use of visual metaphor and word play. Dental students preferentially expressed their understanding of anatomy and physiology kinesthetically, creating art that required manual dexterity as well as through choreography and dance. Combining art-making with basic science curricular learning invited the medical and dentistry students to link their understanding to different modes of expression and a non-biomedical way of knowing. Subsequent incorporation of the student-generated cardiac art into lectures exposed the entire class to creative pictorial expressions of anatomy, physiology and pathophysiology.


Infliximab for the treatment of active scleritis.
This study aimed to evaluate the possible safety and effectiveness of infliximab in patients with active scleritis. Prospective, nonrandomized, open-label pilot study (Protocol No. 04-EI-0065). Five patients with active anterior scleritis. This single-centre, pilot study of infliximab for the treatment of active anterior scleritis was conducted at the National Eye Institute, National Institutes of Health, between 2003 and 2007. Scleritis patients with active disease who had used at least 1 conventional immunosuppressive agent in the past were included. Primary outcome was a 2-step decrease in scleral inflammation within 14 weeks. Patients received infliximab (5 mg/kg) at baseline, at weeks 2 and 6, and every 4 weeks through week 30, after which the infusion interval was increased (week 36, 48). All patients met the primary outcome by achieving quiescence of their active scleritis by week 14 with no additional immunosuppressives. However, after 14 weeks 1 patient developed new-onset intraocular inflammation that did not respond to reinduction and was terminated from the study. Side effects attributable to infliximab included ear infection with transient decreased hearing, urinary tract infection, lower respiratory tract infection, and facial rash in 1 patient and urinary tract infection, diarrhea, upper respiratory tract infection, nasal congestion and headache, mouth sores, head tremor, and occasional numbness and tingling in extremities in another patient, all of which resolved spontaneously or with appropriate treatment. Infliximab may be considered as a viable option in treating patients with active scleritis; however, patients should be monitored closely for potentially serious side effects.


Multiscale Diffusion Entropy Analysis for the Detection of Crucial Events in Cardiac Pathology.
The significance of crucial events in explaining the dynamics of a physiological system has only been recently emerging. Crucial events are yet to be fully understood and implemented in clinical applications of physiological signal processing. This paper proposes the application of modified diffusion entropy (MDEA) and novel multiscale diffusion entropy analyses (MSDEA) on measuring the temporal complexity of the ECG time series to improve crucial events detection performance. Thirty samples of each of three groups of ECG datasets from PhysioNet with recordings of cardiac arrhythmia (ARR), congestive heart failure (CHF) and normal sinus rhythm (NSR) were analyzed using MDEA with stripes followed by MSDEA. Healthy NSR ECGs showed an approximate 15% greater inverse power law (IPL) and scaling δ indices than pathologic CHF and ARR signals. Additionally, the scaling indices for the pathologic groups showed higher standard deviations, indicating that crucial events determined by MDEA reveal latent differences in ECG complexity that could better be investigated across multiple time scales of temporally decomposed signals using MSDEA which combines multiscale entropy (MSE) and MDEA. Hence, MSDEA showed an improved, clearer discrimination between the healthy and pathological cardiac signals (p<0.0005) characterized by a range of NSR complexity indices twice the range of the pathological values associated with ARR and CHF across twenty temporal scales as well as more reliable trend lines (R2>=0.95).Clinical Relevance- This research proposes a novel and enhanced diagnostic discrimination across healthy and pathologic cardiac conditions based on biomedical signal processing of ECG recordings utilizing the principle of crucial events detection.


Feasibility of using DNA-immobilized nanocellulose-based immunoadsorbent for systemic lupus erythematosus plasmapheresis.
The goal of this project was to study the feasibility of using a DNA-immobilized nanocellulose-based immunoadsorbent for possible application in medical apheresis such as systemic lupus erythematosus (SLE) treatment. Calf thymus DNA was bound to high surface area nanocellulose membrane at varying concentrations using UV-irradiation. The DNA-immobilized samples were characterized with scanning electron microscopy, atomic force microscopy, and phosphorus elemental analysis. The anti-ds-DNA IgG binding was tested in vitro using ELISA. The produced sample showed high affinity in vitro to bind anti-ds-DNA-antibodies from mice, as much as 80% of added IgG was bound by the membrane. Furthermore, the binding efficiency was quantitatively dependent on the amount of immobilized DNA onto nanocellulose membrane. The described nanocellulose membranes are interesting immunoadsorbents for continued clinical studies.


Synergistic effects of childhood adversity and polygenic risk in first-episode psychosis: the EU-GEI study.
A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone. We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case-control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR)exposure and PRS - ORexposure - ORPRS + 1] with adjustment for potential confounders. There was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95% confidence interval (CI) -1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95% CI -6.25 to 20.88). Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates.


Addressing Ageism and Ethnocultural Diversity With a Photo Essay Project.
By 2050, the percentage of older adults in the United States will double. By 2060, nonmajority individuals will comprise nearly half of our older adult population. Therefore, nursing students must have learning experiences that prepare them to care for a diverse population of older adults when they enter practice. Photo-elicitation and a photo essay project was initiated in an Aging and Health in Global Communities course in which 75 students created and presented photo essays of a diverse group of older adults. Through spending time with older adults to create a photo essay, students ably portrayed lives rich in meaning and ethnocultural heritage. The natural intersection of aging and diversity that occurred in the photo essays enlightened students to the rich experience of age and the similarities and unique differences in the lives of the older people portrayed. [J Nurs Educ. 2021;60(1):44-47.].


Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-ranging study.
To compare efficacy and safety of various doses of tofacitinib, an oral Janus kinase inhibitor, with placebo in patients with active ankylosing spondylitis (AS, radiographic axial spondyloarthritis). In this 16-week (12-week treatment, 4-week washout), phase II, multicentre, dose-ranging trial, adult patients with active AS were randomised (N=51, 52, 52, 52, respectively) to placebo or tofacitinib 2, 5 or 10 mg twice daily. The primary efficacy endpoint was Assessment of SpondyloArthritis International Society 20% improvement (ASAS20) response rate at week 12. Secondary endpoints included objective measures of disease activity, patient-reported outcomes and MRI of sacroiliac joints and spine. Safety was monitored. Emax model analysis of the primary endpoint predicted a tofacitinib 10 mg twice daily ASAS20 response rate of 67.4%, 27.3% higher than placebo. Supportive normal approximation analysis demonstrated tofacitinib 5 mg twice daily ASAS20 response rate significantly higher than placebo (80.8% vs 41.2%; p<0.001); tofacitinib 2 and 10 mg twice daily demonstrated greater response rate than placebo (51.9% and 55.8%, respectively; not significant). Secondary endpoints generally demonstrated greater improvements with tofacitinib 5 and 10 mg twice daily than placebo. Objective (including MRI) endpoints demonstrated clear dose response. Adverse events were similar across treatment groups with no unexpected safety findings. Dose-dependent laboratory outcome changes returned close to baseline by week 16. Tofacitinib 5 and 10 mg twice daily demonstrated greater clinical efficacy versus placebo in reducing signs, symptoms and objective endpoints of active AS in adult patients with a similar 12-week safety profile as reported in other indications. NCT01786668.


The emerging role of the microcirculation in clinical medicine.
Although research on microcirculation has expanded rapidly in the last 20 years, clinical evaluation of microcirculation, as an entity, has not achieved any status in the United States. Three aspects of microcirculation are presented, wherein clinical applications exist or on the verge of existing. Biomicroscopy is the direct observation of, and measurements within, the microcirculation is superficial areas of the body. Not only can the pattern of the microcirculation be examined and related to microcirculatory function but also the intravascular relationships among red cells, leukocytes, and platelets can be studied. Rheology includes measurement of the interactions among plasma and cellular elements during flow within the microcirculation. Unfortunately, rheologic factors are generally ignored in thinking about hemodynamics. The concept of the optimal hematocrit has great clinical relevance in both acute and chronic disease. Transvascular fluid and solute exchange can be evaluated in the body as a whole and in individual organs by relatively noninvasive techniques. Such evaluations provide useful information about the natural progress and the effect of treatment of a variety of serious diseases. Microcirculation, as an entity, is a quantitative science in its own right and ought to be actively applied in clinical medicine.


Age and puberty differences in stress responses during a public speaking task: do adolescents grow more sensitive to social evaluation?
During adolescence pubertal development is said to lead to an increase in general stress sensitivity which might create a vulnerability for the emergence of psychopathology during this period. However, the empirical evidence for increasing stress sensitivity is scarce and mixed. Biological responses (salivary cortisol and alpha-amylase) were investigated during a social-evaluative stressor, the Leiden Public Speaking Task, in 295 nine to 17-year olds. Specific attention was paid to different elements of the task, that is anticipation to and delivery of the speech. Biological reactivity to the speech task increased with age and puberty, particularly during anticipation. Current findings support the idea that biological stress sensitivity increases during adolescence, at least in response to a social-evaluative situation. The increasing stress sensitivity appears related to both age and pubertal maturation, but unique contribution could not be distinguished. The importance of measuring anticipation is discussed.


The COVID-19 outbreak and stock market reactions: Evidence from Australia.
We examine how the Australian stock market responded to the uncertainties created by the COVID-19 pandemic and whether the stimulus package offered by the Government helped restore confidence in the market. This study finds a negative stock market reaction to the pandemic announcement, however, among two stimulus packages related announcements, the market reacted positively only to "JobKeeper" package. The cross-sectional results suggest that the smallest, least profitable and value portfolios suffered more during the pandemic. Finally, size and liquidity are found to be the significant drivers of abnormal returns. These results generally hold for a battery of robustness checks.


Quick-start of full-scale anaerobic digestion (AD) using aeration.
A conventional 1300 m(3) continuously stirred anaerobic tank reactor at the city of Boden, north Sweden, which was receiving a feed of both sewage sludge and food waste, was put out of operation due to the build-up of a float phase. The reactor was emptied and cleaned. At start-up there was no methanogenic sludge available, so an unconventional start-up procedure was applied: The reactor was rapidly (8 days with 1200 kg of total solids (TS) added daily) filled with thickened, and slightly acidic sewage sludge, showing only slight methane generation, which was subsequently heated to 55 °C. Then compressed air was blown into the digester and within a month a fully functional methanogenic culture was established. The transfer from acidogenic to methanogenic conditions happened in about one week. As a start-up technique this is fast and cost efficient, it only requires the access of a compressor, electricity and a source of air. In total, about 16 tonnes of oxygen were used. It is proposed that this method may also be used as an operational amendment technique, should a reactor tend to acidify.


Altered cardiac excitation-contraction coupling in ventricular myocytes from spontaneously diabetic BB rats.
Cardiac excitation-contraction (E-C) coupling abnormalities in chemically induced diabetes have been well defined. Heart dysfunction has also been reported in diabetes of genetic origin. The purpose of this study was to determine whether heart dysfunction in genetically predisposed diabetes is attributable to impaired E-C coupling at the cellular level. Myocytes were isolated from 1-yr-old BioBreed (BB) spontaneously diabetic-prone (BB/DP) rats and their diabetic-resistant littermates (BB/DR). Mechanical properties were evaluated by use of a video edge-detection system. Myocytes were electrically stimulated at 0.5 Hz. The contractile properties analyzed included peak shortening (PS), time-to-peak shortening (TPS), time-to-90% relengthening (TR(90)), and maximal velocities of shortening and relengthening (+/-dL/dt). Intracellular Ca(2+) handling was evaluated with fura 2 fluorescent dye. Myocytes from spontaneously diabetic hearts exhibited a depressed PS, prolonged TPS and TR(90), and reduced +/-dL/dt. Consistent with the mechanical response, myocytes from the BB/DP group displayed reduced resting and peak intracellular Ca(2+) concentration associated with a slowed Ca(2+)-transient decay. Furthermore, myocytes from BB/DP hearts were less responsive to increases in extracellular Ca(2+) and norepinephrine and equally responsive to increases in stimulation frequency and KCl compared with those from the BB/DR group. These results suggest that the genetic diabetic state produces altered cardiac E-C coupling, in part, because of abnormalities of the myocyte, similar to that demonstrable after chemically induced diabetes or during human diabetes.


Diagnostic performance of low-dose computed tomography screening for lung cancer over five years.
Low-dose computed tomography (LD-CT) screening can reduce lung cancer mortality; however, it is essential to improve nodule management protocols. We analyze the performance of the diagnostic protocol of the Continuous Observation of SMOking Subjects single-center screening study, after long-term follow-up. Between 2004 and 2005, 5203 asymptomatic high-risk individuals (≥20 pack-years, aged 50 years or older) were enrolled to undergo annual LD-CT for 5 years. Nodules 5 mm or smaller underwent repeat LD-CT a year later. Nodules larger than 5.0 mm and 8.0 mm or smaller received LD-CT 3 to 6 months later. Nodules larger than 8.0 mm or growing underwent CT-positron emission tomography. True positives were any stage prevalent lung cancer, progressing nodules diagnosed at stage 1, localized multifocal cancer, or new nodules diagnosed at any stage. False negatives were progressing nodules diagnosed at stage >1. False positives were benign nodules resected surgically. Compliance was 79% over 5 years; 175 primary lung cancers were detected (0.76% per year), 136 (77.7%) were N0M0 and three were interval cancers. Eleven second primary lung cancers were diagnosed. Resectability was 87.4%; postoperative mortality 0.6%. Recall was 6.4% overall, 10.1% at baseline. False negatives were 14 of 175 (8%). Protocol sensitivity was 158 of 175 (90%); specificity 4994 of 5028 (99.4%); positive predictive value was 158 of 187 (84.5%); and negative predictive value was 4994 of 5016 (99.7%). Twenty-nine of 204 (14.2%) benign lesions were diagnosed surgically. Five-year overall and cancer-specific survival were 78% (95% confidence interval, 72-84) and 82% (95% confidence interval, 76%-88%) respectively. The performance of the CT protocol was satisfactory with an acceptable number of benign lesions biopsied surgically, low recall rate, and good oncological outcomes. However, interval and advanced cancers, and misdiagnoses, need to be reduced, perhaps by risk modeling and use of serum markers.


Peroxisome proliferator activated receptor gamma, CCAAT/enhancer-binding protein alpha, and cell cycle status regulate the commitment to adipocyte differentiation.
Terminal differentiation of stem cells is characterized by cessation of cell proliferation as well as changes in cell morphology associated with the differentiated state. For adipocyte differentiation, independent lines of evidence show that the transcription factors peroxisome proliferator activated receptor gamma (PPARgamma) and CCAAT/enhancer-binding protein alpha (C/EBPalpha) as well as the tumor suppressor retinoblastoma (Rb) protein are essential. How these proteins promote adipocyte conversion and how they function cooperatively during the differentiation process remain unclear. We have used retinoic acid (RA) inhibition of adipogenesis to investigate these issues. RA blocked adipogenesis of 3T3-L1 cells induced to differentiate by ectopic expression of PPARgamma and C/EBPalpha independently or together. However, under these circumstances RA was only effective at preventing adipogenesis when added prior to confluence, suggesting that factors involved in regulation of the cell cycle might play a role in establishing the commitment state of adipogenesis that is insensitive to RA. During differentiation of wild type 3T3 L1 preadipocytes, we found that Rb protein is hyperphosphorylated early in adipogenesis, corresponding to previously quiescent cells re-entering the cell cycle, and later becomes hypophosphorylated. The data suggest that, together with the coexpression of PPARgamma and C/EBPalpha, permanent exit from the cell cycle establishes the irreversible commitment to adipocyte differentiation.


Increasing completion of asparaginase treatment in childhood acute lymphoblastic leukaemia (ALL): summary of an expert panel discussion.
Insufficient exposure to asparaginase therapy is a barrier to optimal treatment and survival in childhood acute lymphoblastic leukaemia (ALL). Three important reasons for inactivity or discontinuation of asparaginase therapy are infusion related reactions (IRRs), pancreatitis and life-threatening central nervous system (CNS). For IRRs, real-time therapeutic drug monitoring (TDM) and premedication are important aspects to be considered. For pancreatitis and CNS thrombosis one key question is if patients should be re-exposed to asparaginase after their occurrence.An expert panel met during the Congress of the International Society for Paediatric Oncology in Lyon in October 2019 to discuss strategies for diminishing the impact of these three toxicities. The panel agreed that TDM is particularly useful for optimising asparaginase treatment and that when a tight pharmacological monitoring programme is established premedication could be implemented more broadly to minimise the risk of IRR. Re-exposure to asparaginase needs to be balanced against the anticipated risk of leukemic relapse. However, more prospective data are needed to give clear recommendations if to re-expose patients to asparaginase after the occurrence of severe pancreatitis and CNS thrombosis.


17-β-estradiol up-regulates apolipoprotein genes expression during osteoblast differentiation in vitro.
Apolipoproteins are of great physiological importance and are associated with different diseases. Many independent studies of patterns of gene expression during osteoblast differentiation have been described, and some apolipoproteins have been induced during this process. 17-β-estradiol (E2) may enhance osteoblast physiological function. However, no studies have indicated whether E2 can modulate the expression of apolipoproteins during osteoblast differentiation in vitro. The aim of the current study was to observe the regulation of apolipoprotein mRNA expression by E2 during this process. Primary osteoblasts were collected from the calvaria of newborn mice and were subjected to osteoblast differentiation in vitro with serial concentrations of E2. RNA was isolated on days 0, 5, and 25 of differentiation. Real-time PCR was performed to analyze the levels of apolipoprotein mRNA. Results showed that during osteoblast differentiation all of the apolipoprotein genes were up-regulated by E2 in a dose-dependent manner. Moreover, only ApoE was strongly induced during the mineralization of cultured osteoblasts. This result suggests that ApoE might be involved in osteoblast differentiation. The hypothesis is that E2 promotes osteoblast differentiation by up-regulating ApoE gene expression, though further study is needed to confirm this hypothesis.


Fine-mapping and evolutionary history of R-BPMV, a dominant resistance gene to Bean pod mottle virus in Phaseolus vulgaris L.
R-BPMV is located within a recently expanded TNL cluster in the Phaseolus genus with suppressed recombination and known for resistance to multiple pathogens including potyviruses controlled by the I gene. Bean pod mottle virus (BPMV) is a comovirus that infects common bean and legumes in general. BPMV is distributed throughout the world and is a major threat on soybean, a closely related species of common bean. In common bean, BAT93 was reported to carry the R-BPMV resistance gene conferring resistance to BPMV and linked with the I resistance gene. To fine map R-BPMV, 182 recombinant inbred lines (RILs) derived from the cross BAT93 × JaloEEP558 were genotyped with polymerase chain reaction (PCR)-based markers developed using genome assemblies from G19833 and BAT93, as well as BAT93 BAC clone sequences. Analysis of RILs carrying key recombination events positioned R-BPMV to a target region containing at least 16 TIR-NB-LRR (TNL) sequences in BAT93. Because the I cluster presents a suppression of recombination and a large number of repeated sequences, none of the 16 TNLs could be excluded as R-BPMV candidate gene. The evolutionary history of the TNLs for the I cluster were reconstructed using microsynteny and phylogenetic analyses within the legume family. A single I TNL was present in Medicago truncatula and lost in soybean, mirroring the absence of complete BPMV resistance in soybean. Amplification of TNLs in the I cluster predates the divergence of the Phaseolus species, in agreement with the emergence of R-BPMV before the separation of the common bean wild centers of diversity. This analysis provides PCR-based markers useful in marker-assisted selection (MAS) and laid the foundation for cloning of R-BPMV resistance gene in order to transfer the resistance into soybean.


Benzhydryldimethylsilyl allylic silanes: syntheses and applications to
A new silyl group, the benzhydryldimethylsilyl group, has been developed that is easily synthesized and that undergoes facile oxidation. The [3 + 2] annulation reactions of allylic silanes with this silyl group provide a variety of highly substituted five-membered carbocycles and heterocycles with high stereoselectivities. The silyl groups of these cyclic compounds have been oxidized to hydroxyl groups to demonstrate the general synthetic utility of the method.


Combined effects of hypertension and diabetes mellitus with stroke among Thais in the central region of Thailand: a cross-sectional study.
To determine associations of individual and combined effects of hypertension and diabetes with stroke among Thais aged 55 years and older Cross-sectional data from national screening program for metabolic syndrome in Thailand for the year 2010 among participants who lived in central region of Thailand were used. The number of participants was 13,268 in the analysis. The prevalence of stroke was 0.9%. Associations between hypertension and diabetes found among participants who had hypertension only, diabetes only, and both hypertension and diabetes were: 8.99 (95% CI 4.63-17.43), 3.72 (95% CI 1.03-13.37), 10.48 (95% CI 4.54-24.20) among males and 5.16 (95% CI 2.29-11.53), 6.55 (95% CI 2.19-19.55), and 9.29 (95% CI 3.81-22.68) among females, respectively. The present study suggested dramatically the strong effects of the association of combined hypertension and diabetes with stroke. Strengthening health promotion programs for the prevention of hypertension, diabetes, especially having both diseases after screening, is important among Thai population.