Expression of nuclear lamin A and muscle-specific proteins in differentiating muscle cells in ovo and in vitro.
Primary cultures and tissue samples of chicken embryonic muscle were immunologically probed for the expression of muscle-specific proteins, such as myosin heavy chain and the tropomyosins, as well as for the nuclear lamina protein, lamin A. As determined by quantitative immunoblotting, the expression of lamin A and the muscle-specific proteins were at low levels or absent in predifferentiation myoblasts both in vitro and in ovo. During differentiation, an increase of lamin A expression preceded the induction to high levels of expression of muscle-specific proteins. Immunofluorescence staining of chicken embryonic muscle cells in culture also indicates an accumulation of lamin A before the induction of muscle-specific proteins expression. Furthermore, the accumulation of lamin A reached a plateau before the muscle-specific proteins during muscle development. In two dimensional NEPHGE gel analysis of immunoprecipitated lamin A, no detectable change in the ratio of the acidic/basic isoelectric variants of lamin A was observed during myogenesis. A potential role for lamin A in the mechanisms which underlie the differential and coordinate expression of muscle-specific genes is proposed.


Rat diaphragm mitochondria have lower intrinsic respiratory rates than mitochondria in limb muscles.
The mitochondrial content of skeletal muscles is proportional to activity level, with the assumption that intrinsic mitochondrial function is the same in all muscles. This may not hold true for all muscles. For example, the diaphragm is a constantly active muscle; it is possible that its mitochondria are intrinsically different compared with other muscles. This study tested the hypothesis that mitochondrial respiration rates are greater in the diaphragm compared with triceps surae (TS, a limb muscle). We isolated mitochondria from diaphragm and TS of adult male Sprague Dawley rats. Mitochondrial respiration was measured by polarography. The contents of respiratory complexes, uncoupling proteins 1, 2, and 3 (UCP1, UCP2, and UCP3), and voltage-dependent anion channel 1 (VDAC1) were determined by immunoblotting. Complex IV activity was measured by spectrophotometry. Mitochondrial respiration states 3 (substrate and ADP driven) and 5 (uncoupled) were 27 ± 8% and 24 ± 10%, respectively, lower in diaphragm than in TS (P < 0.05 for both comparisons). However, the contents of respiratory complexes III, IV, and V, UCP1, and VDAC1 were higher in diaphragm mitochondria (23 ± 6, 30 ± 8, 25 ± 8, 36 ± 15, and 18 ± 8% respectively, P ≤ 0.04 for all comparisons). Complex IV activity was 64 ± 16% higher in diaphragm mitochondria (P ≤ 0.01). Mitochondrial UCP2 and UCP3 content and complex I activity were not different between TS and diaphragm. These data indicate that diaphragm mitochondria respire at lower rates, despite a higher content of respiratory complexes. The results invalidate our initial hypothesis and indicate that mitochondrial content is not the only determinant of aerobic capacity in the diaphragm. We propose that UCP1 and VDAC1 play a role in regulating diaphragm aerobic capacity.


Morphologic and immunophenotypic features of a case of acute monoblastic leukemia with unusual positivity for Glycophorin-A.
Acute monoblastic leukemia (AMoL) is characterized by cells with highly undifferentiated morphology. Cytochemistry with non-specific esterases is negative in up to 20% of cases. Immunophenotyping by flow cytometry has an essential role in diagnosing such a subtype of leukemia and a multiparametric approach with a wide monoclonal antibody panel is necessary. We describe a case of AMoL with morphology resembling either plasma blasts or very immature erythroblasts. Diagnosis was made by alpha-naphtyl-acetate esterase staining and with immunophenotyping, which was made with a wide monoclonal antibody panel. Blasts were positive for monocytic markers. Most of leukemic cells, however, were positive for Glycophorin-A. The presence of Glycophorin-A, which is considered as a specific marker of the erythroid lineage, has never been reported previously in cases of AMoL. This peculiar immunophenotype might be interpreted as deriving from a common myelo-erythroid precursor undergone leukemic transformation.


Cortical origin of functional recovery in the somatosensory cortex of the adult mouse after thalamic lesion.
To study the degree and time course of the functional recovery in the somatosensory cortex (SI) after an excitotoxic lesion in the adult mouse thalamus, metabolic activity was determined in SI at various times points post-lesion. Immediately after the lesion, metabolic activity in the thalamically deafferented part of SI was at its lowest value but increased progressively at subsequent time points. This was seen in all cortical layers; however, layers I and Vb recovered more rapidly than layers II, III, IV, Va and VI. Removal of the mystacial whiskers corresponding to the deafferented area, 5 weeks after cortical recovery, produced a subsequent 32% drop in metabolic activity, demonstrating peripheral sensory activation of this part of the cortex. Tracing experiments revealed that the deafferented cortex did not receive a novel thalamic input but that cortico-cortical and contralateral barrel cortex projections to this area were reinforced. We conclude that the cortical functional recovery after a thalamic lesion is, at least partially, due to modified cortico-cortical and callosal projections to the deafferented cortical area.


Is there an upper limit of intracranial pressure in patients with severe head injury if cerebral perfusion pressure is maintained?
Authors of recent studies have championed the importance of maintaining cerebral perfusion pressure (CPP) to prevent secondary brain injury following traumatic head injury. Data from these studies have provided little information regarding outcome following severe head injury in patients with an intracranial pressure (ICP) greater than 40 mm Hg, however, in July 1997 the authors instituted a protocol for the management of severe head injury in patients with a Glasgow Coma Scale score lower than 9. The protocol was focused on resuscitation from acidosis, maintenance of a CPP greater than 60 mm Hg through whatever means necessary as well as elevation of the head of the bed, mannitol infusion, and ventriculostomy with cerebrospinal fluid drainage for control of ICP. Since the institution of this protocol, nine patients had a sustained ICP greater than 40 mm Hg for 2 or more hours, and five of these had an ICP greater than 75 mm Hg on insertion of the ICP monitor and later experienced herniation and expired within 24 hours. Because of the severe nature of the injuries demonstrated on computerized tomography scans and their physical examinations, these patients were not aggressively treated under this protocol. The authors vigorously attempted to maintain a CPP greater than 60 mm Hg with intensive fluid resuscitation and the administration of pressor agents in the four remaining patients who had developed an ICP higher than 40 mm Hg after placement of the ICP monitor. Two patients had an episodic ICP greater than 40 mm Hg for more than 36 hours, the third patient had an episodic ICP greater than of 50 mm Hg for more than 36 hours, and the fourth patient had an episodic ICP greater than 50 mm Hg for more than 48 hours. On discharge, all four patients were able to perform normal activities of daily living with minimal assistance and experience ongoing improvement. Data from this preliminary study indicate that intense, aggressive management of CPP can lead to good neurological outcomes despite extremely high ICP. Aggressive CPP therapy should be performed and maintained even though apparently lethal ICP levels may be present. Further study is needed to support these encouraging results.


Use of body armor protection with fighting load impacts soldier performance and kinematics.
The purpose of this evaluation was to examine how increasing body armor protection with and without a fighting load impacted soldiers' performance and mobility. Thirteen male soldiers performed one performance (repeated 30-m rushing) and three mobility tasks (walk, walk over and walk under) with three different body armor configurations and an anterior fighting load. Increasing body armor protection, decreased soldier performance, as individual and total 30-m rush times were significantly longer with greater protection. While increasing body armor protection had no impact on mobility, i.e. significant effect on trunk and lower limb biomechanics, during the walk and walk over tasks, greater protection did significantly decrease maximum trunk flexion during the walk under task. Adding fighting load may negatively impact soldier mobility, as greater maximum trunk extension was evident during the walk and walk over tasks, and decreased maximum trunk flexion exhibited during the walk under task with the fighting load.


Silhouette Orientation Volumes for Efficient Fall Detection in Depth Videos.
A novel method to detect human falls in depth videos is presented in this paper. A fast and robust shape sequence descriptor, namely the Silhouette Orientation Volume (SOV), is used to represent actions and classify falls. The SOV descriptor provides high classification accuracy even with a combination of simple associated models, such as Bag-of-Words and the Naïve Bayes classifier. Experiments on the public SDU-Fall dataset show that this new approach achieves up to 91.89% fall detection accuracy with a single-view depth camera. The classification rate is about 5% higher than the results reported in the literature. An overall accuracy of 89.63% was obtained for the six-class action recognition, which is about 25% higher than the state of the art. Moreover, a perfect silhouette-based action recognition rate of 100% is achieved on the Weizmann action dataset.


[Late sequelae of violence seen from victims' perspective].
Hospital accident and emergency (A&E) departments frequently treat victims of interpersonal violence. This study of 1,451 victims treated at the A&E departments of Aarhus University Hospital during a one-year period (1993-94) aims at illuminating some of the sequelae of victims. A questionnaire survey was carried out two years later to obtain information on medical after-treatment, the extent of sick leaves, and the victims' personal costs. One in two assault victims needed further medical treatment. 7.5% were admitted to hospital and 20% were referred to the out-patient clinic in the hospital or to follow-up treatment in general practice. The median sick leave period was eight days. Two years after the violence took place, 21.8% of all assault victims claimed that they had cosmetic sequelae, 14.7% had persistent pain. 38.1% said they were afraid to enter certain neighbourhoods or places; 41.2% had frequently or occasionally thought about the assault. The study has revealed some aspects of the personal costs, discomfort and trouble that victims of violence experience.


Washington State recreational marijuana legalization: parent and adolescent perceptions, knowledge, and discussions in a sample of low-income families.
In November 2012, Washington State and Colorado became the first states in the United States to legalize recreational marijuana use for adults, and Uruguay became the first country to allow the cultivation, distribution, possession, and use of marijuana. One possible consequence of these changes is increased adolescent marijuana use. Parents may mitigate this adverse consequence; however, whether parents and adolescents have accurate knowledge about the laws and are discussing marijuana use in light of the law changes is unknown. We examine perceptions, knowledge, and parent-child discussions about Washington State's recreational marijuana law in a sample of low-income families. Participants were a subset of families (n = 115) in an ongoing study that originally recruited parents and adolescents from middle schools in Tacoma, Washington. In summer 2013, when students were entering the 11(th) grade, students and their parents were asked questions about the recreational marijuana law. Participants perceived that their marijuana-related attitudes and behaviors changed little as a result of the law, and displayed uncertainty about what is legal and illegal. Most parents reported discussing the new law with their children but only occasionally, and conversations emphasized household rules, particularly among parent lifetime marijuana users compared to non-users. Conclusions/Importance: Results suggest that there should be a public health campaign focused on families that provides clear information about the recreational marijuana laws.


Velocity dependent friction laws in contact mode atomic force microscopy.
Friction forces in the tip-sample contact govern the dynamics of contact mode atomic force microscopy. In ambient conditions typical contact radii between tip and sample are in the order of a few nanometers. In order to account for the large interaction area the dynamics of contact mode atomic force microscope (AFM) is investigated under the assumption of a multi-asperity contact interface between tip and sample. Thus, the kinetic friction force between tip and sample is the product of the real contact area between both solids and the interfacial shear strength. The velocity strengthening of the lateral force is modeled assuming a logarithmic relationship between shear-strength and velocity. Numerical simulations of the system dynamics with this empirical model show the existence of two different regimes in contact mode AFM: steady sliding and stick-slip where the tip undergoes periodically stiction and kinetic friction. The state of the system depends on the scan velocity as well as on the velocity dependence of the interfacial friction force between tip and sample. Already small viscous damping contributions in the tip-sample contact are sufficient to suppress stick-slip oscillations.


HLA associations in classical Hodgkin lymphoma: EBV status matters.
The pathogenesis of classical Hodgkin lymphoma (cHL) involves environmental and genetic factors. To explore the role of the human leukocyte antigen (HLA) genes, we performed a case-control genotyping study in 338 Dutch cHL patients using a PCR-based sequence-specific oligonucleotide probe (SSOP) hybridization approach. The allele frequencies were compared to HLA typings of more than 6,000 controls. The age of the cHL patients varied between 13 and 81 years with a median of 35 years. Nodular sclerosis subtype was the most common subtype (87%) and EBV was detected in 25% of the cHL patients. HLA-B5 was significantly increased and HLA-DR7 significantly decreased in the total cHL patient population as compared to controls. Two class II associations were observed to be specific for the EBV- cHL population with an increase of HLA-DR2 and HLA-DR5. Allele frequencies of HLA-A1, HLA-B37 and HLA-DR10 were significantly increased in the EBV+ cHL population; these alleles are in strong linkage disequilibrium and form a common haplotype in Caucasians. The allele frequency of HLA-A2 was significantly decreased in the EBV+ cHL population. Analysis of haplotypes with a frequency of >1% revealed a significant increase of HLA-A2-B7-DR2 in EBV- cHL as compared to controls. SSOP association analysis revealed significant differences between EBV+ and EBV- cHL patients for 19 probes that discriminate between HLA-A*01 and HLA-A*02. In conclusion, the HLA-A1 and HLA-A2 antigens and not specific single nucleotide variants shared by multiple alleles are responsible for the association with EBV+ cHL. Furthermore several new protective and predisposing HLA class I and II associations for the EBV+, the EBV- and the entire cHL population were identified.


Insights into virulence: structure classification of the Vibrio parahaemolyticus RIMD mobilome.
The pandemic Vpar strain RIMD causes seafood-borne illness worldwide. Previous comparative genomic studies have revealed pathogenicity islands in RIMD that contribute to the success of the strain in infection. However, not all virulence determinants have been identified, and many of the proteins encoded in known pathogenicity islands are of unknown function. Based on the EOCD database, we used evolution-based classification of structure models for the RIMD proteome to improve our functional understanding of virulence determinants acquired by the pandemic strain. We further identify and classify previously unknown mobile protein domains as well as fast evolving residue positions in structure models that contribute to virulence and adaptation with respect to a pre-pandemic strain. Our work highlights key contributions of phage in mediating seafood born illness, suggesting this strain balances its avoidance of phage predators with its successful colonization of human hosts.


Heritability and genetic correlations of total and differential somatic cell count with milk yield and composition traits in Italian Simmental cows.
Costs of production have deeply increased each year in the last decades, breeders are continuously looking for more cost effective and more efficient ways to produce milk. Despite the major signs of progress in productivity, it is fundamental to optimize rather than maximize the performances of the dairy cows. Mastitis is still a highly prevalent disease in the dairy sector which causes several economic losses and environmental impact. Its accurate and early diagnosis is crucial to improve profitability of dairy cows and contribute to a more sustainable dairy industry. Among mastitis reduction strategies, there is the urgent need to implement breeding objectives to select cows displaying mastitis resistance by investigating the genetic mechanisms at the base of the inflammatory response. Therefore, in this study we aimed to further understand the genetic background of the Differential Somatic Cell Count (DSCC), which provides thorough insights on the actual inflammatory status of the mammary glands. The objectives of this study were to estimate on a cohort of 20,215 Italian Simmental cows over a 3-year period: i) the heritability and repeatability values of Somatic Cell Score (SCS) and DSCC, ii) the genetic and phenotypic correlations between these 2 traits and milk production and milk composition traits, iii) the heritability and repeatability values of SCS and DSCC within class of udder health status. Heritability was low both for SCS (0.06) and DSCC (0.08), whereas the repeatability values for these traits were 0.43 and 0.36, suggesting that the magnitude of cow permanent environmental effect for these traits is remarkable. The genetic and phenotypic correlation of SCS with DSCC was 0.612 and 0.605, respectively. Since both significantly differed from the unit, we must consider those traits as different ones. This latter aspect corroborates the need to consider the DSCC as a further indicator of inflammatory status which might be implemented in the Simmental breed genetic evaluation. It is worthy to mention that heritability estimates for SCS and DSCC were the highest in healthy cows compared with the other udder health classes. This implies that when the udder health status changes, it is most likely due to environmental factors rather than aspects related to the animal's genetics. In contrast, the highest additive genetic variance and heritability found for SCS and DSCC in the healthy group might reveal the potential to further implement breeding strategies to select for healthier animals.


Mechanical Considerations for Electrospun Nanofibers in Tendon and Ligament Repair.
Electrospun nanofibers possess unique qualities such as nanodiameter, high surface area to volume ratio, biomimetic architecture, and tunable chemical and electrical properties. Numerous studies have demonstrated the potential of nanofibrous architecture to direct cell morphology, migration, and more complex biological processes such as differentiation and extracellular matrix (ECM) deposition through topographical guidance cues. These advantages have created great interest in electrospun fibers for biomedical applications, including tendon and ligament repair. Electrospun nanofibers, despite their nanoscale size, generally exhibit poor mechanical properties compared to larger conventionally manufactured polymer fiber materials. This invites the question of what role electrospun polymer nanofibers can play in tendon and ligament repair applications that have both biological and mechanical requirements. At first glance, the strength and stiffness of electrospun nanofiber grafts appear to be too low to fill the rigorous loading conditions of these tissues. However, there are a number of strategies to enhance and tune the mechanical properties of electrospun nanofiber grafts. As researchers design the next-generation electrospun tendon and ligament grafts, it is critical to consider numerous physiologically relevant mechanical criteria and to evaluate graft mechanical performance in conditions and loading environments that reflect in vivo conditions and surgical fixation methods.


Active transportation and public transportation use to achieve physical activity recommendations? A combined GPS, accelerometer, and mobility survey study.
Accurate information is lacking on the extent of transportation as a source of physical activity, on the physical activity gains from public transportation use, and on the extent to which population shifts in the use of transportation modes could increase the percentage of people reaching official physical activity recommendations. In 2012-2013, 234 participants of the RECORD GPS Study (French Paris region, median age = 58) wore a portable GPS receiver and an accelerometer for 7 consecutive days and completed a 7-day GPS-based mobility survey (participation rate = 57.1%). Information on transportation modes and accelerometry data aggregated at the trip level [number of steps taken, energy expended, moderate to vigorous physical activity (MVPA), and sedentary time] were available for 7,644 trips. Associations between transportation modes and accelerometer-derived physical activity were estimated at the trip level with multilevel linear models. Participants spent a median of 1 h 58 min per day in transportation (8.2% of total time). Thirty-eight per-cent of steps taken, 31% of energy expended, and 33% of MVPA over 7 days were attributable to transportation. Walking and biking trips but also public transportation trips with all four transit modes examined were associated with greater steps, MVPA, and energy expenditure when compared to trips by personal motorized vehicle. Two simulated scenarios, implying a shift of approximately 14% and 33% of all motorized trips to public transportation or walking, were associated with a predicted 6 point and 13 point increase in the percentage of participants achieving the current physical activity recommendation. Collecting data with GPS receivers, accelerometers, and a GPS-based electronic mobility survey of activities and transportation modes allowed us to investigate relationships between transportation modes and physical activity at the trip level. Our findings suggest that an increase in active transportation participation and public transportation use may have substantial impacts on the percentage of people achieving physical activity recommendations.


Ancient Wheat Diet Delays Diabetes Development in a Type 2 Diabetes Animal Model.
The main objective was to investigate the physiological effects of ancient wheat whole grain flour diets on the development and progression of type 2 diabetes in Zucker diabetic fatty (ZDF) rats, and specifically to look at the acute glycemic responses. An intervention study was conducted, involving 40 ZDF rats consuming one of 5 different diets (emmer, einkorn, spelt, rye and refined wheat) for 9 weeks. Refined wheat flour and whole grain rye flour were included as negative and positive controls, respectively. After 9 weeks of intervention, a downregulation of the hepatic genes PPAR-α, GLUT2, and SREBP-1c was observed in the emmer group compared to the control wheat group. Likewise, expression of hepatic SREBP-2 was lower for emmer, einkorn, and rye compared with the control group. Furthermore, spelt and rye induced a low acute glycemic response. The wheat group had higher HDL- and total cholesterol levels. Ancient wheat diets caused a downregulation of key regulatory genes involved in glucose and fat metabolism, equivalent to a prevention or delay of diabetes development. Spelt and rye induced a low acute glycemic response compared to wheat.


Disruption of Circadian Rhythms by Ambient Light during Neurodevelopment Leads to Autistic-like Molecular and Behavioral Alterations in Adult Mice.
Although circadian rhythms are thought to be essential for maintaining body health, the effects of chronic circadian disruption during neurodevelopment remain elusive. Here, using the "Short Day" (SD) mouse model, in which an 8 h/8 h light/dark (LD) cycle was applied from embryonic day 1 to postnatal day 42, we investigated the molecular and behavioral changes after circadian disruption in mice. Adult SD mice fully entrained to the 8 h/8 h LD cycle, and the circadian oscillations of the clock proteins, PERIOD1 and PERIOD2, were disrupted in the suprachiasmatic nucleus and the hippocampus of these mice. By RNA-seq widespread changes were identified in the hippocampal transcriptome, which are functionally associated with neurodevelopment, translational control, and autism. By western blotting and immunostaining hyperactivation of the mTOR and MAPK signaling pathways and enhanced global protein synthesis were found in the hippocampi of SD mice. Electrophysiological recording uncovered enhanced excitatory, but attenuated inhibitory, synaptic transmission in the hippocampal CA1 pyramidal neurons. These functional changes at synapses were corroborated by the immature morphology of the dendritic spines in these neurons. Lastly, autistic-like animal behavioral changes, including impaired social interaction and communication, increased repetitive behaviors, and impaired novel object recognition and location memory, were found in SD mice. Together, these results demonstrate molecular, cellular, and behavioral changes in SD mice, all of which resemble autistic-like phenotypes caused by circadian rhythm disruption. The findings highlight a critical role for circadian rhythms in neurodevelopment.


Identification of a novel proline-arginine motif involved in CIN85-dependent clustering of Cbl and down-regulation of epidermal growth factor receptors.
CIN85 is a multidomain adaptor protein implicated in Cbl-mediated down-regulation of receptor tyrosine kinases. CIN85 binding to Cbl is increased after growth factor stimulation and is critical for targeting receptor tyrosine kinases to clathrin-mediated endocytosis. Here we report the identification of a novel polyproline-arginine motif (PXXXPR), specifically recognized by the SH3 domains of CIN85 and its homologue CMS/CD2AP. This motif was indispensable for CIN85 binding to Cbl/Cbl-b, to other CIN85 SH3 domains' effectors, and for mediating an intramolecular interaction between the SH3-A domain and the proline-rich region of CIN85. Individual SH3 domains of CIN85 bound to PXXXPR peptides of Cbl/Cbl-b with micromolar affinities, whereas an extended structure of two or three SH3 domains bound with higher stoichiometry and increased affinity to the same peptides. This enabled full size CIN85 to simultaneously interact with multiple Cbl molecules, promoting their clustering in mammalian cells. The ability of CIN85 to cluster Cbl was important for ligand-induced stabilization of CIN85.Cbl.epidermal growth factor receptor complexes, as well as for epidermal growth factor receptor degradation in the lysosome. Thus, specific interactions of CIN85 SH3 domains with the PXXXPR motif in Cbl play multiple roles in down-regulation of receptor tyrosine kinases.


[The hemodiafiltration with endogenous reinfusion reduces the erythroid progenitor inhibition by uremic serum].
Anemia in end-stage renal disease (ESRD) patients shows a lower proliferation of erythroid progenitor cells such as burst forming unit-erythroid (BFU-E) than in normal subjects. As on-line hemodiafiltration with endogenous reinfusion(HFR) is thought to have a better biocompatibility and a wide range of uremic toxin removal, we compared the effect of serum obtained pre- and post-standard hemodialysis (HD) and HFR dialysis performed in four ESRD patients with proliferation in normal subject) (controls) bone marrow BFU-E. Mononuclear fraction was obtained by Ficoll-Hypaque density centrifugation and studies were performed in three different conditions: standard culture, adding serum from controls, adding serum from ESRD patients pre- and post HD and HFR dialysis. BFU-E were counted after 14 days with an inverted microscope and expressed as average scores from two dishes. Standardization between experiments was checked with a control culture for each experimental culture. The BFU-E proliferation rate was clearly reduced by adding serum from ESRD patients either pre-HD or pre-HFR. However, while this inhibition was exacerbated by post-HD serum, it showed a significant reduction with post-HFR serum. This effect could be due to the removal of uremic toxins or to a lower dialysis-induced cytokine release, both mechanisms involved in erythropoiesis inhibition in ESRD.


BDI personal medical assistant agents: The case of trauma tracking and alerting.
Personal assistant agents can have an important role in healthcare as a smart technology to support physicians in their daily work, helping to tackle the increasing complexity of their task environment. In this paper we present and discuss a personal medical assistant agent technology for trauma documentation and management, based on the Belief-Desire-Intention (BDI) architecture. The purpose of the personal assistant agent is twofold: to assist the Trauma Team in doing precision tracking during a trauma resuscitation, so as to (automatically) produce an accurate documentation of the trauma, and to generate alerts at real-time, to be eventually displayed either on smart-glasses or room-display.


A novel epithelial-mesenchymal transition (EMT)-related gene signature of predictive value for the survival outcomes in lung adenocarcinoma.
Lung adenocarcinoma (LUAD) is a remarkably heterogeneous and aggressive disease with dismal prognosis of patients. The identification of promising prognostic biomarkers might enable effective diagnosis and treatment of LUAD. Aberrant activation of epithelial-mesenchymal transition (EMT) is required for LUAD initiation, progression and metastasis. With the purpose of identifying a robust EMT-related gene signature (E-signature) to monitor the survival outcomes of LUAD patients. In The Cancer Genome Atlas (TCGA) database, least absolute shrinkage and selection operator (LASSO) analysis and cox regression analysis were conducted to acquire prognostic and EMT-related genes. A 4 EMT-related and prognostic gene signature, comprising dickkopf-like protein 1 (DKK1), lysyl oxidase-like 2 (LOXL2), matrix Gla protein (MGP) and slit guidance ligand 3 (SLIT3), was identified. By the usage of datum derived from TCGA database and Western blotting analysis, compared with adjacent tissue samples, DKK1 and LOXL2 protein expression in LUAD tissue samples were significantly higher, whereas the trend of MGP and SLIT3 expression were opposite. Concurrent with upregulation of epithelial markers and downregulation of mesenchymal markers, knockdown of DKK1 and LOXL2 impeded the migration and invasion of LUAD cells. Simultaneously, MGP and SLIT3 silencing promoted metastasis and induce EMT of LUAD cells. In the TCGA-LUAD set, receiver operating characteristic (ROC) analysis indicated that our risk model based on the identified E-signature was superior to those reported in literatures. Additionally, the E-signature carried robust prognostic significance. The validity of prediction in the E-signature was validated by the three independent datasets obtained from Gene Expression Omnibus (GEO) database. The probabilistic nomogram including the E-signature, pathological T stage and N stage was constructed and the nomogram demonstrated satisfactory discrimination and calibration. In LUAD patients, the E-signature risk score was associated with T stage, N stage, M stage and TNM stage. GSEA (gene set enrichment analysis) analysis indicated that the E-signature might be linked to the pathways including GLYCOLYSIS, MYC TARGETS, DNA REPAIR and so on. In conclusion, our study explored an innovative EMT based prognostic signature that might serve as a potential target for personalized and precision medicine.


Dietary fat and the beta-adrenergic-mediated chronotropic response in the rat.
We have investigated the effect of dietary fat on isoproterenol-stimulated and propranolol-inhibited heart rate in the rat. In the first experiment, weanling male Sprague-Dawley rats were fed diets containing 10% butter (10B), 10% corn oil (10C) or 9% butter/1% corn oil (10M) for 4 wk. Heart rate was determined in response to increasing i.v. doses of isoproterenol. The percent stimulation at the highest dose of isoproterenol (100 microM) was found to be significantly higher (P less than 0.05) in the 10C-fed group than either the 10B- and 10M-fed groups. A similar study investigated the effect of propranolol inhibition of heart rate in low-fat (10C and 10B) as well as high-fat (25C) corn oil- and high-fat (25B) butter-fed animals. Heart rate was elevated with a constant i.v. infusion of isoproterenol and the inhibitory effect of propranolol was determined. The ED50 was found not to depend on the level of fat, but was found to be significantly lower in the corn oil-fed animals than in those red butter fat (P less than 0.05). Thus, animals appear to be more sensitive to these beta-adrenergic agonists/antagonists when fed a diet containing corn oil rather than butter fat as the lipid source.


The effectiveness of general practice-based health checks on health behaviour and incidence on non-communicable diseases in individuals with low socioeconomic position: a randomised controlled trial in Denmark.
The effectiveness of health checks aimed at the general population is disputable. However, it is not clear whether health checks aimed at certain groups at high risk may reduce adverse health behaviour and identify persons with metabolic risk factors and non-communicable diseases (NCDs). To assess the effect of general practice-based health checks on health behaviour and incidence on NCDs in individuals with low socioeconomic position. Individuals with no formal education beyond lower secondary school and aged 45-64 years were randomly assigned to the intervention group of a preventive health check or to control group of usual care in a 1:1 allocation. Randomisation was stratified by gender and 5-year age group. Due to the real-life setting, blinding of participants was only possible in the control group. Effects were analysed as intention to treat (ITT) and per protocol. The trial was undertaken in 32 general practice units in Copenhagen, Denmark. Invitation to a prescheduled preventive health check from the general practitioner (GP) followed by a health consultation and an offer of follow-up with health risk behaviour change or preventive medical treatment, if necessary. Smoking status at 12-month follow-up. Secondary outcomes included status in other health behaviours such as alcohol consumption, physical activity and body mass index (measured by self-administered questionnaire), as well as incidence of metabolic risk factors and NCDs such as hypertension, hypercholesterolaemia, chronic obstructive pulmonary disease, diabetes mellitus, hypothyroidism, hyperthyroidism and depression (drawn from national healthcare registries). 1104 participants were included in the study. For the primary outcome, 710 participants were included in the per protocol analysis, excluding individuals who did not attend the health check, and 1104 participants were included in the ITT analysis. At 12-month follow-up, 37% were daily smokers in the intervention group and 37% in the control group (ORs=0.99, 95% CI: 0.76 to 1.30). No difference in health behaviour nor in the incidence of metabolic risk factors and NCDs between the intervention and control group were found. Side effects were comparable across the two groups. The lack of effectiveness may be due to low intensity of intervention, a high prevalence of metabolic risk factors and NCDs among the participants at baseline as well as a high number of contacts with the GPs in general or to the fact that general practices are not an effective setting for prevention. NCT01979107.


Not just the needle: the state of HIV-prevention science among substance users and future directions.
Efforts to prevent HIV transmission among substance-using populations have focused primarily among injection drug users, which have produced measurable reductions in HIV incidence and prevalence. By contrast, the majority of substances used worldwide are administered by noninjectable means, and there is a dearth of HIV prevention interventions that target noninjecting substance users. Increased surveillance of trends in substance use, especially cocaine (including crack) and methamphetamine, in addition to new and emerging substances (eg, synthetic cannabinoids, cathinones, and other amphetamine analogs) are needed to develop and scale up effective and robust interventions for populations at risk for HIV transmission via sexual behaviors related to noninjection substance use. Strategies are needed that address unique challenges to HIV prevention for substance users who are HIV infected and those who are HIV uninfected and are at high risk. We propose a research agenda that prioritizes (1) combination HIV-prevention strategies in substance users; (2) behavioral HIV prevention programs that reduce sexual transmission behaviors in nontreatment seeking individuals; (3) medical and/or behavioral treatments for substance abuse that reduce/eliminate substance-related sexual transmission behaviors; and (4) structural interventions to reduce HIV incidence.


Intracellular tetraethylammonium ions enhance group Ia excitatory post-synaptic potentials evoked in cat motoneurones.
Single fibre group Ia excitatory post-synaptic potentials (e.p.s.p.s) were recorded in cat spinal motoneurones after the neurones were injected with tetraethylammonium (TEA) ions. TEA injection increased the peak amplitude of most e.p.s.p.s. The time course of e.p.s.p.s generated at the soma was unaffected, but the time course of e.p.s.p.s generated in the dendrites was prolonged. The membrane time constant did not change after TEA injection. Somatic e.p.s.p.s were voltage clamped after TEA was injected. The reversal potential for these e.p.s.p.s was more positive than for e.p.s.p.s unaffected by TEA. Composite e.p.s.p.s added linearly, or greater than linearly, whereas in motoneurones without TEA they added linearly or less than linearly. The enhanced amplitude and prolonged time course observed in dendritic e.p.s.p.s after TEA injection was reduced by small hyperpolarizing currents. Greater than linear summation of composite e.p.s.p.s was converted to linear summation by small hyperpolarizing currents. The increase in somatic e.p.s.p.s was attributed to a more positive reversal potential for the e.p.s.p.s. We suggest that TEA decreases the relative permeability of K+ in the subsynaptic channels. We propose that in the presence of TEA, dendritic depolarization activates an inward current which amplifies and prolongs synaptic potentials spreading towards the soma.


Amelogenin Gene - The Pioneer in Gender Determination from Forensic Dental Samples.
In the event of any mass fatality incident, DNA analysis plays a vital role in disaster victim identification. Teeth are one of the most resistant structures in the human body that resist decomposition hence making them prime choice for extracting DNA for identification of individuals. Polymerase Chain Reaction (PCR) analysis that target regions of Amelogenin gene have become the method of choice for sex determination of biological samples. Determining the sex of a given DNA sample from either dental pulp or dentin of tooth and help in identification of missing persons and disaster victims. In our study 50 teeth samples were studied and they were subjected to various environmental conditions along with freshly extracted teeth taken as control for duration of one month and three months. Pulpal tissue was retrieved from the teeth specimens by access opening of root canals and for incinerated samples, the specimens were crushed. From the DNA that was extracted from the dental pulp sample Amelogenin gene locus was used for sex determination by amplifying a segment of X-Y homologous gene locus through PCR analysis. ANOVA test and t-test proved to be statistically significant and 100% retrieval rate was observed in samples. Pulpal tissue along with degenerating odontoblastic processes yield sufficient amount of DNA for gender determination when subjected to various forensic conditions with maximum accuracy.


[Nursing care systematization in rehabilitation unit, in accordance to Horta's conceptual model].
The utilization of a conceptual model in the Nursing Attendance Systemization allows the development of activities based on theoretical references that can guide the implantation and the implementation of nursing proceedings in hospitals. In this article we examine the option made for the implementation of the Horta's conceptual model in the construction of a nursing attendance system in the Rehabilitation Unit of a public hospital located in the Federal District of Brazil. Through the utilization of these theoretical references it was possible to make available a data collection tool based on the basic human needs. The identification of these needs made possible the construction of the hierarchically disposed pyramid of the neurological patients' modified basic needs. Through this reference paper we intend to elaborate the prescription and nursing evolution based in the concepts and standards of the Horta's nursing process, making possible the inter-relationship of all phases of this attendance methodology.


DNA transposition between plant organellar genomes.
Higher plant mitochondrial and chloroplast DNAs are known to share extensive sequence homologies. The present work addresses issues raised by these initial observations: (1) what is the distributive pattern of ctDNA sequences among different mitochondrial genomes, (2) what is the frequency of DNA transposition between the two organelles, (3) are the transposed ctDNA sequences transcribed? The results to be presented demonstrate that many ctDNA sequences, including identified genes, are widespread in mitochondrial genomes and in some cases are highly conserved. However, the distribution of any one particular sequence is sporadic, even within a plant family. Preliminary data, obtained in studies of watermelon, raise the possibility that some mtDNA transcripts share homology with ctDNA sequences.


Cholera surveillance in Uganda: an analysis of notifications for the years 2007-2011.
Cholera outbreaks have occurred periodically in Uganda since 1971. The country has experienced intervals of sporadic cases and localized outbreaks, occasionally resulting in prolonged widespread epidemics. Cholera surveillance data reported to the Uganda Ministry of Health from 2007 through 2011 were reviewed to determine trends in annual incidence and case fatality rate. Demographic characteristics of cholera cases were analyzed from the national line list for 2011. Cases were analyzed by district and month of report to understand the geographic distribution and identify any seasonal patterns of disease occurrence. From 2007 through 2011, Uganda registered a total of 7615 cholera cases with 181 deaths (case fatality rate = 2.4%). The absolute number of cases and incidence per 100 000 varied from year to year with the highest incidence occurring in 2008 following heavy rainfall and flooding in eastern Uganda. For 2011, cholera cases occurred in 1.6 times more males than females. The geographical areas affected by the outbreaks shifted each year, with the exception of a few endemic districts. No clear seasonal trends in cholera occurrence were identified for this time period. We observed an overall decline in cases reported during the 5 years under review. During this period, concerted efforts were made by the Ugandan government and development partners to educate communities on proper sanitation and hygiene and provide safe water and timely treatment. Mechanisms to ensure timely and complete cholera surveillance data are reported to the national level should continue to be strengthened.


Kaposi's sarcoma-associated herpesvirus open reading frame 50/Rta protein activates the entire viral lytic cycle in the HH-B2 primary effusion lymphoma cell line.
Rta, the gene product of Kaposi's sarcoma-associated herpesvirus (KSHV) encoded mainly in open reading frame 50 (ORF50), is capable of activating expression of viral lytic cycle genes. What was not demonstrated in previous studies was whether KSHV Rta was competent to initiate the entire viral lytic life cycle including lytic viral DNA replication, late-gene expression with appropriate kinetics, and virus release. In HH-B2, a newly established primary effusion lymphoma (PEL) cell line, KSHV ORF50 behaved as an immediate-early gene and autostimulated its own expression. Expression of late genes, ORF65, and K8.1 induced by KSHV Rta was eliminated by phosphonoacetic acid, an inhibitor of viral DNA polymerase. Transfection of KSHV Rta increased the production of encapsidated DNase-resistant viral DNA from HH-B2 cells. Thus, introduction of an ORF50 expression plasmid is sufficient to drive the lytic cycle to completion in cultured PEL cells.


Physical activity education in the undergraduate curricula of all UK medical schools: are tomorrow's doctors equipped to follow clinical guidelines?
Physical activity (PA) is a cornerstone of disease prevention and treatment. There is, however, a considerable disparity between public health policy, clinical guidelines and the delivery of physical activity promotion within the National Health Service in the UK. If this is to be addressed in the battle against non-communicable diseases, it is vital that tomorrow's doctors understand the basic science and health benefits of physical activity. The aim of this study was to assess the provision of physical activity teaching content in the curricula of all medical schools in the UK. Our results, with responses from all UK medical schools, uncovered some alarming findings, showing that there is widespread omission of basic teaching elements, such as the Chief Medical Officer recommendations and guidance on physical activity. There is an urgent need for physical activity teaching to have dedicated time at medical schools, to equip tomorrow's doctors with the basic knowledge, confidence and skills to promote physical activity and follow numerous clinical guidelines that support physical activity promotion.


Applying the heteroskedastic ordered probit model on injury severity for improved age and gender estimation.
Driver characteristics have been linked to the frequency and severity of car crashes. Among these, age and gender have been shown to impact both the possibility and severity of a crash. Previous studies have used standard ordered probit (OP) models to analyze crash data, and some research has suggested heteroskedastic ordered probit (HETOP) could provide improved model fit. The objective of this paper is to evaluate potential improvements of the heteroskedastic ordered probit (HETOP) model compared to the standard ordered probit (OP) model in crash analysis, by examining the effect of gender across age on injury severity among drivers. This paper hypothesizes that the HETOP model can provide a better fit to crash data, by allowing heteroskedasticity in the distribution of injury severity across driver age and gender. Data for 20,222 crashes were analyzed for North Carolina from 2016 to 2018, which represents the state with the highest number of fatalities per 100 million vehicle miles traveled amongst available crash data from the Highway Safety Information System. Darker lighting conditions, severe road surface conditions, and less severe weather were associated with increased injury severity. For driver demographics, the probability of severe injuries increased with age and for male drivers. Moreover, the variance of severity increased with age disproportionately within and across genders, and the HETOP was able to account for this. The results of the two applied approaches revealed that HETOP model outperformed the standard OP model when measuring the effects of age and gender together in injury severity analysis, due to the heteroskedasticity in injury severity within gender and age. The HETOP statistical method presented in this paper can be more broadly applied across other contexts and combinations of independent variables for improved model prediction and accuracy of causal variables in traffic safety.


Petroleum hydrocarbon rhizoremediation and soil microbial activity improvement via cluster root formation by wild proteaceae plant species.
Rhizoremediation potential of different wild plant species for total (aliphatic) petroleum hydrocarbon (TPH)-contaminated soils was investigated. Three-week-old seedlings of Acacia inaequilatera, Acacia pyrifolia, Acacia stellaticeps, Banksia seminuda, Chloris truncata, Hakea prostrata, Hardenbergia violacea, and Triodia wiseana were transplanted in a soil contaminated with diesel and engine oil as TPH at pollution levels of 4,370 (TPH1) and 7,500 (TPH2) mg kg-1, and an uncontaminated control (TPH0). After 150 days, the presence of TPH negatively affected the plant growth, but the growth inhibition effect varied between the plant species. Plant growth and associated root biomass influenced the activity of rhizo-microbiome. The presence of B. seminuda, C. truncata, and H. prostrata significantly increased the TPH removal rate (up to 30% compared to the unplanted treatment) due to the stimulation of rhizosphere microorganisms. No significant difference was observed between TPH1 and TPH2 regarding the plant tolerance and rhizoremediation potentials of the three plant species. The presence of TPH stimulated cluster root formation in B. seminuda and H. prostrata which was associated with enhanced TPH remediation of these two members of Proteaceae family. These results indicated that B. seminuda, C. truncata, and H. prostrata wild plant species could be suitable candidates for the rhizoremediation of TPH-contaminated soil.


Frontrunners in the race to develop a SARS-CoV-2 vaccine.
Numerous studies continue to be published on the COVID-19 pandemic that is being caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Given the rapidly evolving global response to SARS-CoV-2, here we primarily review the leading COVID-19 vaccine strategies that are currently in Phase III clinical trials. Nonreplicating viral vector strategies, inactivated virus, recombinant protein subunit vaccines, and nucleic acid vaccine platforms are all being pursued in an effort to combat the infection. Preclinical and clinal trial results of these efforts are examined as well as the characteristics of each vaccine strategy from the humoral and cellular immune responses they stimulate, effects of any adjuvants used, and the potential risks associated with immunization such as antibody-dependent enhancement. A number of promising advancements have been made toward the development of multiple vaccine candidates. Preliminary data now emerging from phase III clinical trials show encouraging results for the protective efficacy and safety of at least 3 frontrunning candidates. There is hope that one or more will emerge as potent weapons to protect against SARS-CoV-2.


Chronic coccydynia in adolescents. A series of 53 patients.
Little is known about coccydynia in adolescents. The aim of this study was to explore causes, clinical and imaging features and response to treatment of chronic coccydynia in adolescents. This was a cohort study. The study included patients followed up at a specialized consultation in a university hospital. A series of 53 adolescent patients with chronic coccydynia were followed for 1-4 years. Investigations included dynamic X-ray films, with a magnetic resonance imaging scan of the coccyx in 26/53. Treatment was by coccygeal steroid injection or non-steroidal anti-inflammatory drugs (NSAIDs). Amitriptyline or coccygectomy were used as second-line treatment. Outcomes were assessed at a consultation two months after the treatment, then between one to four years later, by telephone interview, questionnaires and by a visual analogue scale (VAS). Fifty-one adult patients with coccydynia formed the control group. In 20 cases (37.7%) the coccydynia was subsequent to trauma. Obesity was not a risk factor. Abnormal mobility was rarer and spicules more frequent compared to adult patients (P<0.001); 11/27 MRI scans showed a hypersignal within the disc or adjacent bone and 6/27 a hypersignal surrounding the tip of the coccyx (bursitis). Initial treatment was a coccygeal steroid injection for 41 patients and NSAIDs for 12. Ten were given amitriptyline and 3 a coccygectomy. At final assessment, there was no pain or almost no pain in 32/53 (60.4%), moderate pain and functional impairment in 12/53 (22.6%) and severe pain and functional impairment in 9/53 (17%). Coccydynia in adolescents differs from coccydynia in adults. A MRI scan is helpful and should be obligatory for diagnosis. Prognosis is relatively good. Our results should help clinicians manage this rare and debilitating condition.


Why is the GMN motif conserved in the CorA/Mrs2/Alr1 superfamily of magnesium transport proteins?
Members of the CorA/Mrs2/Alr1 superfamily of transport proteins mediate magnesium uptake in all kingdoms of life. Family members have a low degree of sequence conservation but are characterized by a conserved extracellular loop. While the degree of sequence conservation in the loop deviates to some extent between family members, the GMN family signature motif is always present. Structural and functional data imply that the loop plays a central role in magnesium selectivity, and recent biochemical data suggest it is crucial for stabilizing the pentamer in the magnesium-free (putative open) conformation. In this study, we present a detailed structure-function analysis of the extracellular loop of CorA from Thermotoga maritima, which provides molecular insight into how the loop mediates these two functions. The data show that loop residues outside of the GMN motif can be substituted if they support the pentameric state, but the residues of the GMN motif are intolerant to substitution. We conclude that G(312) is absolutely required for magnesium uptake, M(313) is absolutely required for pentamer integrity in the putative open conformation, and N(314) plays a role in both of these functions. These observations suggest a molecular reason why the GMN motif is conserved throughout the CorA/Mrs2/Alr1 superfamily.


Evaluation of the skin sensitizing potency of chemicals by using the existing methods and considerations of relevance for elicitation.
The Technical Committee of Classification and Labelling dealing with harmonized classification of substances and classification criteria under Directive 67/548/EEC on behalf of the European Commission nominated an expert group on skin sensitization in order to investigate further the possibility for potency consideration of skin sensitizers for future development of the classification criteria. All substances and preparations should be classified on the basis of their intrinsic properties and should be labelled accordingly with the rules set up in the Directive 67/548/EEC. The classification should be the same under their full life cycle and in the case that there is no harmonized classification the substance or preparation should be self-classified by the manufacturer in accordance with the same criteria. The Directive does not apply to certain preparations in the finished state, such as medical products, cosmetics, food and feeding stuffs, which are subject to specific community legislation. The main questions that are answered in this report are whether it would be possible to give detailed guidance on how to grade allergen potency based on the existing methods, whether such grading could be translated into practical thresholds and whether these could be set for both induction and elicitation. Examples are given for substances falling into various potency groups for skin sensitization relating to results from the local lymph node assay, the guinea pig maximization test, the Buehler method and human experience.


Epidemiology of the reported severity of copperhead (Agkistrodon contortrix) snakebite.
The goal of this study was to analyze trends in the annual rates of reported medical outcomes of US copperhead (Agkistrodon contortrix) snakebites published in the annual reports of the American Association of Poison Control Centers in the course of 26 years. This was a retrospective analysis of medical outcomes for copperhead snakebite victims who developed fatal, major, moderate, minor, or no effects. The annual rates for these medical outcomes were calculated by dividing the annual number of patients in each outcome category by the total annual number of people reported as being bitten by copperheads. Poisson and negative binomial regression were used to examine trends in annual rates. From 1983 through 2008, the incidence rate of copperhead snakebites causing no effect significantly decreased by 12.1%/year (incidence rate ratio [IRR] 0.879; 95% confidence interval [CI] 0.848-0.911]. From 1985 through 2008, the incidence rate of minor outcomes significantly decreased by 2.3%/year (IRR 0.977; 95% CI 0.972-0.981), whereas the rate of moderate outcomes significantly increased by 2.8%/year (IRR 1.028; 95% CI 1.024-1.033). The rate of major outcomes did not significantly change. One fatality was reported in 2001. Annual rates of copperhead snakebites producing no effects and minor outcomes significantly decreased, those producing moderate outcomes significantly increased, and those producing major outcomes did not significantly change in a 26-year period.


The Stigma of Epilepsy among Patients Attending the Epilepsy Clinic at Connaught Hospital, Sierra Leone.
Epilepsy is one of the world's most common neurological disorders with about eighty percent of cases living in low and middle-income countries. Due to superstitious cultural and traditional beliefs in Sub-Saharan Africa, the stigma associated with epilepsy is particularly disabling. Stigma negatively affects the psychosocial wellbeing of people with epilepsy (PWE) and their acceptance of medical treatment. Very limited studies have been done on the types and extent of stigma in PWE in Sierra Leone. This study will assess the extent and correlates of perceived and enacted stigma among patients attending the epilepsy clinic at Connaught hospital in Freetown, Sierra Leone. Using a semi-structured questionnaire to identify both perceived and enacted stigma, a cross-sectional descriptive study was conducted among patients attending the epilepsy clinic at Connaught hospital aged ten years and above with no major psychiatric co-morbidity. Frequency of stigma and socio-demographic and clinical correlates of stigma were determined. Of the 128 patients, (9 below 18 years) 57.8% were males. Participants had a mean age of 32.9 years. 53.9% and 79.9% of participants reported experiencing perceived and enacted stigma, respectively. Longer duration of illness and being single correlated with perceived stigma, while lower educational achievement and early age of onset of seizure correlated with enacted stigma. A seizure frequency of more than two attacks a month was significantly related to both forms of stigma. The level of epilepsy-related social stigma is high in Sierra Leone. This is likely due to poor community education, leading to misconceptions and biases. An appropriate educational intervention coupled with effective clinical management of cases is needed to mitigate epilepsy-related stigma. L'épilepsie est l'un des troubles neurologiques les plus courants dans le monde, avec environ quatre-vingts pour cent des cas vivant dans des pays à revenu faible et intermédiaire. En raison des croyances culturelles et traditionnelles superstitieuses en Afrique subsaharienne, la stigmatisation associée à l'épilepsie est particulièrement handicapante. La stigmatisation affecte négativement le bien-être psychosocial des personnes épileptiques (PWE) et leur acceptation du traitement médical. Très peu d'études ont été menées sur les types et l'étendue de la stigmatisation chez les PWE en Sierra Leone. Cette étude évaluera l'étendue et les corrélats de la stigmatisation perçue et manifeste chez les patients fréquentant la clinique de l'épilepsie à l'hôpital Connaught à Freetown, Sierra Leone. À l'aide d'un questionnaire semi-structuré pour identifier la stigmatisation perçue et manifeste, une étude descriptive transversale a été menée chez des patients fréquentant la clinique de l'épilepsie à l'hôpital Connaught, âgés de dix ans et plus, sans co-morbidité psychiatrique majeure. La fréquence de la stigmatisation et les corrélats socio-démographiques et cliniques de la stigmatisation ont été déterminés. Sur les 128 patients (9 de moins de 18 ans), 57,8% étaient des hommes. Les participants avaient un âge moyen de 32,9 ans. 53,9% et 79,9% des participants ont signalé avoir éprouvé une stigmatisation perçue et manifeste, respectivement. Une durée plus longue de la maladie et le fait d'être célibataire étaient corrélés à la stigmatisation perçue, tandis qu'un niveau d'éducation inférieur et un jeune âge de début des crises étaient corrélés à la stigmatisation manifeste. Une fréquence de crises de plus de deux attaques par mois était significativement liée aux deux formes de stigmatisation. Le niveau de stigmatisation sociale liée à l'épilepsie est élevé en Sierra Leone. Cela est probablement dû à une éducation communautaire insuffisante, conduisant à des idées fausses et des préjugés.Une intervention éducative appropriée couplée à une gestion clinique efficace des cas est nécessaire pour atténuer la stigmatisation liée à l'épilepsie. Épilepsie, Manifeste, Perçue, Stigmatisation, Sierra Leone.


Established Cotton Stainer Gut Bacterial Mutualists Evade Regulation by Host Antimicrobial Peptides.
Symbioses with microorganisms are ubiquitous in nature and confer important ecological traits to animal hosts but also require control mechanisms to ensure homeostasis of the symbiotic interactions. In addition to protecting hosts against pathogens, animal immune systems recognize, respond to, and regulate mutualists. The gut bacterial symbionts of the cotton stainer bug, Dysdercus fasciatus, elicit an immune response characterized by the upregulation of c-type lysozyme and the antimicrobial peptide pyrrhocoricin in bugs with their native gut microbiota compared to that in dysbiotic insects. In this study, we investigated the impact of the elicited antimicrobial immune response on the established cotton stainer gut bacterial symbiont populations. To this end, we used RNA interference (RNAi) to knock down immunity-related genes hypothesized to regulate the symbionts, and we subsequently measured the effect of this silencing on host fitness and on the abundance of the major gut bacterial symbionts. Despite successful downregulation of target genes by both ingestion and injection of double-stranded RNA (dsRNA), the silencing of immunity-related genes had no effect on either host fitness or the qualitative and quantitative composition of established gut bacterial symbionts, indicating that the host immune responses are not actively involved in the regulation of the nutritional and defensive gut bacterial mutualists. These results suggest that close associations of bacterial symbionts with their hosts can result in the evolution of mechanisms ensuring that symbionts remain insensitive to host immunological responses, which may be important for the evolutionary stability of animal-microbe symbiotic associations.IMPORTANCE Animal immune systems are central for the protection of hosts against enemies by preventing or eliminating successful infections. However, in the presence of beneficial bacterial mutualists, the immune system must strike a balance of not killing the beneficial symbionts while at the same time preventing enemy attacks. Here, using the cotton stainer bug, we reveal that its long-term associated bacterial symbionts are insensitive to the host's immune effectors, suggesting adaptation to the host's defenses, thereby strengthening the stability of the symbiotic relationship. The ability of the symbionts to elicit host immune responses but remain insensitive themselves may be a mechanism by which the symbionts prime hosts to fight future pathogenic infections.


Vector control in cutaneous leishmaniasis of the old world: a review of literature.
Cutaneous Leishmaniasis (CL), a disfiguring disease, is prevalent in many parts of Pakistan and neighboring Afghanistan. Leishmaniasis is second only to malaria in terms of the number of people affected; it is a major public health issue with significant social stigma. Although the different methods to diagnose and treat the disease are well discussed in the literature, the role of vector control in the prevention of CL has been underemphasized. Both Pubmed and Ovid search engines were used to obtain articles on prevention and control of cutaneous leishmaniasis. These materials were then screened for articles pertaining to vector control only. The World Health Organization's website along with the Cochrane database were also searched for relevant text. From this qualitative review, it can be seen that many effective interventions exist. Considering the multitude of factors involved in transmission of CL and the various effective control measures tried and tested by investigators, an interdisciplinary approach involving more than one of the above interventions would make sense. The interventions selected would then depend on the incidence of CL in that particular area, the population being targeted, the reservoir, the particular vector, the environment, the acceptability/popularity of the intervention, and the availability of funds.


Photoreceptor characteristics in congenic strains of RCS rats.
Three congenic Royal College of Surgeons (RCS) strains of rats have been developed: the RCS-p+ strain, which is a black-eyed dystrophic strain; the pink-eyed RCS-rdy+ strain, which is wild-type (+/+) at the retinal dystrophy (rdy) genetic locus and serves as the control for the inbred, pink-eyed RCS strain; and the black-eyed RCS-rdy+p+ strain, which is +/+ at the rdy locus and serves as the control for the black-eyed RCS-p+ line. Several cytologic features of the photoreceptors were examined in the two control strains, including percentage of cone cells, rod outer segment lengths in different hemispheres of the eye and in different lighting conditions, rate of rod outer segment renewal, and the cyclic pattern of rod outer segment disc shedding. In the pink-eyed RCS-rdy+ strain these features were the same as those in previously described albino rat strains. Most of these features have not been described previously in fully pigmented rats. In the black-eyed RCS-rdy+p+ strain, rod outer segments in the superior eye hemisphere were about 50% longer than those in the inferior hemisphere. The rate of rod outer segment disc synthesis was the same in both hemispheres. Consequently, rod outer segment renewal time depended on outer segment length. This ranged from 9 to 10 days in the inferior hemisphere to 14.6 days in the superior hemisphere.


Metabolic effect of decreasing nonesterified fatty acid levels with acipimox in hyperthyroid patients.
Glucose intolerance is often found in patients with hyperthyroidism, but the pathogenetic mechanisms are not fully understood. Since lipolysis is increased in hyperthyroidism, elevated plasma nonesterified fatty acids (NEFAs) may contribute to abnormal glucose metabolism in hyperthyroidism. The aim of this study was to investigate whether decreasing the plasma NEFA level with acipimox can affect glucose metabolism in hyperthyroidism. We performed an intravenous glucose tolerance test (IVGTT) with acipimox 250 mg or placebo in six untreated hyperthyroid men and six age- and body mass index (BMI)-matched controls. Fasting plasma NEFA levels were significantly higher in the hyperthyroid patients versus the controls (997.0 +/- 303.4 v290.5 +/- 169.1 micromol/L, P < .001). Plasma NEFAs decreased rapidly with acipimox treatment in both controls and hyperthyroid patients. In the controls, the glucose disappearance constant (K(G)) was not different for acipimox treatment versus placebo (2.18 +/- 0.62 v 2.42 +/- 1.00% x min(-1)). In hyperthyroid patients, acipimox treatment increased the K(G) significantly compared with placebo treatment (2.44 +/- 0.84 v 1.58 +/- 0.37% x min(-1), P < .05). Changes in K(G) values with acipimox treatment were inversely correlated with changes in plasma NEFA levels (r = -.65, P < .05). Acipimox treatment increased the acute insulin response (AIR) in hyperthyroid patients (943 +/- 381 v 698 +/- 279 microU/mL x min, P < .05), whereas it did not change the AIR in controls. Changes in the AIR with acipimox treatment correlated significantly with changes in the K(G) (r = .70, P < .05). There was a weak correlation between changes in the AIR with acipimox treatment and changes in plasma NEFA levels (r = -.55, P = .06). In summary, decreasing the plasma NEFA level with acipimox in hyperthyroid patients increases both the K(G) and AIR during an IVGTT. These findings suggest that the abnormal glucose metabolism in hyperthyroidism could be attributed, at least in part, to the increase of plasma NEFA.


The relation of attachment security status to effortful self-regulation: A meta-analysis.
Secure attachment relationships have been described as having a regulatory function in regard to children's emotions, social cognition, and behavior. Although some theorists and researchers have argued that attachment affects children's self-regulation, most attachment theorists have not strongly emphasized this association. The goal of the current meta-analysis was to determine the magnitude of the relation between attachment security status and effortful control (EC)/top-down self-regulation in children up to 18 years of age. One hundred six papers met the inclusion criteria and 101 independent samples were used in analyses. When secure attachment status was compared with insecure attachment status, a significant relation (effect size [ES]) with EC favoring children with a secure attachment was found (100 studies; 20,350 participants; r = .20). A stronger relation was found when the same coder evaluated attachment than when the coder was different and when the measure of attachment was continuous; other moderators were not significant. Securely attached children were higher in EC than their avoidant (r = .10) or resistant (r = .17) counterparts. Children with organized attachments were higher in EC than those with disorganized attachments (r = .17), although this finding could be due to publication bias. For some comparisons of subgroups (B vs. A, B vs. C, and/or D vs. all others), moderation was found by source of information (higher ES for same reporter), age at assessment of EC and/or attachment (higher ES at older ages), method of attachment (lower ES for observational measures), time difference between assessments or research design (higher ESs for smaller time differences and concurrent findings), and published versus unpublished studies (higher ES for unpublished studies for A vs. B). (PsycINFO Database Record


[Isolation, purification and several properties of the extracellular RNA-ase of Bacillus amylozyma].
RNase has been isolated from the cultural broth of Bacillus amylozyma 9a. The dynamics of accumulation of this exocellular enzyme was studied during the growth of the bacterial population, and the optimal conditions for production of the RNase were determined. The enzyme was isolated and purified as follows: precipitation with ammonium sulphate, dialysis, thermal treatment of the enzyme solution, chromatography on DEAE- and CM-celluloses. The enzyme has been purified by 274 times; its specific activity is 3300 units. The preparation contains no DNase, PDEase, and PMEase. The following physical and chemical properties of the enzyme has been studied: molecular weight, thermostability, pH otimum, activation with metal ions.


Clinical experience with Gore-Tex for vocal fold medialization.
Present clinical experience with vocal fold medialization under local anesthesia using a Gore-Tex implant. The procedure consists of placing the implant into a pocket formed by dissection of the inner perichondrium of the thyroid cartilage through a small window made in the thyroid ala. During 2 years, we used this technique preferentially in 13 of the 16 cases of vocal fold medialization (three patients underwent Teflon injection because of a contraindication to local anesthesia). Follow-up was longer than 3 months in 11 cases (mean, 13 mo). Vocal result was analyzed by the means of perceptual analysis and by the measurement of jitter factor. Glottal leakage was evaluated perceptually using videolaryngoscopy, and oral airflow was measured during the production of a vowel. In cases with preoperative aspiration, videofluoroscopy was performed. Implantation was successful in all but one patient in whom extrusion of the implant material occurred. In the latter case, the implant was removed and the patient recuperated his preoperative voice without any other complication. In the 10 other cases, voice improvement assessed by perceptual and objective evaluation was satisfactory. Results compare favorably with those of endoscopic techniques using Teflon or collagen and laryngeal frame surgery techniques using silicone or cartilage. We conclude that Gore-Tex implantation is a simple, reproducible, and minimally invasive procedure for management of selected cases of vocal fold unilateral paralysis in the abductory position.


Quantification in vivo of the effects of insulin on glucose utilization in individual tissues of warm- and cold-acclimated rats.
Cold-acclimation of rats (3 weeks, 4 degrees C) had no effect on basal rates of glucose production or utilization. Under euglycaemic-clamp conditions, in which the circulating insulin concentration was increased by approx. 50 microunits/ml, cold-acclimated rats showed a greater increase in glucose utilization and a greater suppression of endogenous glucose production. Tissue sites of glucose utilization were investigated by using a tracer dose of 2-deoxy-D-[14C]glucose and a glucose metabolic index determined for each tissue. In 5 h-starved warm-acclimated rats, heart had the highest glucose metabolic index. This was increased further by both cold-acclimation and insulin treatment. The glucose metabolic index of skeletal muscle was 3.5-14-fold lower than that of heart, but, as a result of the large muscle mass, skeletal muscle made the largest contribution to whole-body glucose utilization. White and brown adipose tissue had low glucose metabolic indices in warm-acclimated rats under basal conditions, and the indices were not increased by the insulin treatment. However, cold-acclimation produced a significant increase in the glucose metabolic index of brown adipose tissue, but not of white adipose tissue. In contrast with the warm-acclimated rats, insulin treatment of cold-acclimated rats resulted in a marked increase in the glucose metabolic index of brown adipose tissue. The results provide evidence that cold-acclimation produces a selective alteration in the insulin-sensitivity of brown adipose tissue.


Peritoneal dialysis after left ventricular assist device placement.
Patients with refractory congestive heart failure may be considered for implantation of a left ventricular assist device (LVAD). Renal failure after LVAD placement can occur to varying degrees from cardiorenal syndrome (CRS) or due to intrinsic renal disease. Patients with severely impaired renal function after LVAD may require renal replacement therapy (RRT) as a temporary or permanent means of support. We present a unique case of a patient who initiated peritoneal dialysis (PD) 1 year after placement of an LVAD for destination therapy (DT). One year later, PD continues to be successfully utilized by this patient for RRT. There are several proven and theoretical benefits to PD in LVAD patients. Peritoneal dialysis can provide sustained daily ultrafiltration offering greater hemodynamic stability, preservation of residual renal function, and a lower risk of systemic infection. Conversely, limitations to PD include nutritional risks due to peritoneal albumin losses, hyperglycemia, and potential limitations to successful catheter placement. Considering our patient's successful outcome and the potential benefits associated with PD, despite the limitations, we conclude that PD should strongly be considered in patients with LVADs that require RRT.


Multiply imputing missing values arising by design in transplant survival data.
In this article, we address a missing data problem that occurs in transplant survival studies. Recipients of organ transplants are followed up from transplantation and their survival times recorded, together with various explanatory variables. Due to differences in data collection procedures in different centers or over time, a particular explanatory variable (or set of variables) may only be recorded for certain recipients, which results in this variable being missing for a substantial number of records in the data. The variable may also turn out to be an important predictor of survival and so it is important to handle this missing-by-design problem appropriately. Consensus in the literature is to handle this problem with complete case analysis, as the missing data are assumed to arise under an appropriate missing at random mechanism that gives consistent estimates here. Specifically, the missing values can reasonably be assumed not to be related to the survival time. In this article, we investigate the potential for multiple imputation to handle this problem in a relevant study on survival after kidney transplantation, and show that it comprehensively outperforms complete case analysis on a range of measures. This is a particularly important finding in the medical context as imputing large amounts of missing data is often viewed with scepticism.


A person-centred lifestyle change intervention model: working with older people experiencing chronic illness.
A person-centred health promotion model of care to improve self-care and lifestyle changes for older people with chronic illnesses is conceptualized in this paper. The model supports effective interpersonal communication with nurses and health-care consumers and is developed to concept stage. Older people with chronic illnesses who experience stress, anxiety or social isolation are more likely to be admitted and re-admitted to acute hospitals. Interventions to decrease the risk factors are frequently unsuccessful in this patient group. Programmes, led by nurses, aimed at reducing stress, anxiety and social isolation while supporting older people postdischarge from hospital might be successful. The model integrates research from synthesized case studies and a critical literature review. The practices of interrelating four key elements-'construct', 'context', 'process' and 'outcome'-are proposed for nurses to assist patients advancing self-care and lifestyle change. The model is designed for implementation in outpatient, clinic or community settings.


Ethical and intellectual property in the biological sciences.
Ethical concerns on patents in the biological sciences are increased by the prospect of patents for higher life forms. A Canadian patent grants the owner the right to exclude others in Canada from making, using, or selling or offering for sale his or her invention for the term of the patent; however, it does not give the patent owner any positive rights to do likewise. As with other forms of property, the right to make, use, or sell a patented invention may be regulated by other laws or guidelines. In Canada, higher life forms, medical and surgical methods are not patentable subject matter. Unicellular life forms and subcellular material are considered patentable. Decisions on ethical issues are not considered by patent officers. The Patent Office is guided only by legislation. Other regulations by the legislatures can direct public policy and minimize risks.


The soybean mycorrhiza-inducible phosphate transporter gene, GmPT7, also shows localized expression at the tips of vein endings of senescent leaves.
GmPT7 was originally identified as an arbuscular mycorrhiza-inducible gene of soybean that encodes a member of subfamily I in the PHOSPHATE TRANSPORTER 1 family. In the present study, we established conditions under which a number of dwarf soybean plants complete their life cycles in a growth chamber. Using this system, we grew transgenic soybean with a GmPT7 promoter-β-glucuronidase fusion gene and evaluated GmPT7 expression in detail. GmPT7 was highly expressed in mature, but not in collapsed, arbuscule-containing cortical cells, suggesting its importance in the absorption of fungus-derived phosphate and/or arbuscule development. GmPT7 was also expressed in the columella cells of root caps and in the lateral root primordia of non-mycorrhizal roots. The expression of GmPT7 occurred only in the late stage of phosphorus translocation from leaves to seeds, after water evaporation from the leaves ceased, and later than the expression of GmUPS1-2, GmNRT1.7a and GmNRT1.7b, which are possibly involved in nitrogen export. GmPT7 expression was localized in a pair of tracheid elements at the tips of vein endings of senescent leaves. Transmission electron microscopy revealed that the tip tracheid elements in yellow leaves were still viable and had intact plasma membranes. Thus, we think that GmPT7 on the plasma membranes transports phosphate from the apoplast into the tip elements. GmPT7 knockdown resulted in no significant effects, the function of GmPT7 remaining to be clarified. We propose a working model in which phosphate incorporated in vein endings moves to seeds via xylem to phloem transfer.


A Low-Power High Input Range PPG Readout Amplifier with a Current Buffer Input.
This paper presents ultra-low power photoplethysmography (PPG) readout circuits. The proposed system architecture uses a current buffer between the photodiode (PD) and the transimpedance amplifier (TIA) to isolate the large parasitic capacitance of the PD leading to improves the power consumption of the TIA. A class AB topology is exploited at the output of the amplifier, which allows for increased drive capability without the use of auxiliary circuits. The maximum input current range of the TIA is 160 µA, so the large DC current of the input signal does not saturate the circuit. In the LED driver circuit, by varying the duty cycle of a pulse wave modulation (PWM) signal, the ON and OFF times of the circuits. The amplifier and LED driver are manufactured in the 130 nm TSMC CMOS process. The power consumption of the circuits with a duty cycle of 1% is 3.28 µW (at VDD = 1.2V).Clinical Relevance- Vital signs are becoming a very important research topic due to the recent prevalence of COVID-19 and other respiratory diseases. This research aims to develop and interface circuits to monitor vital signs including blood pressure, heart rate, and respiratory rate to study respiratory disease, drug safety, and efficacy.


Genetic and neurodevelopmental influences in autistic disorder.
In the past, autism was considered to be largely psychogenic. However, research in the last 2 decades indicates that autism is largely caused by genetic factors that lead to abnormal brain development. This article reviews research into the genetic and neurodevelopmental factors underlying autism. We review the findings from genetic and brain-imaging studies of autism over the past 15 years and synthesize these findings as a guide for future research. Genome scans and association studies have suggested potential genomic regions and genes, respectively, that may be involved in the etiology of autism, and there have been some replications of these results. Similarly, the findings that brain volume is exaggerated in autism and corpus callosum size is reduced have also been independently replicated. Unfortunately, studies of other subcortical structures remain inconclusive or contradictory. Overwhelming evidence now supports a neurobiological basis for autism. However, further refinements will be needed to guide future studies, particularly to identify the most informative phenotypes to investigate. Additionally, studies examining the role of genetic factors in the brain abnormalities underlying autism will likely lead to further findings that will enhance our understanding of autism's causes.


Plasma total versus bone alkaline phosphatase as markers of bone turnover in hemodialysis patients.
Plasma total versus bone alkaline phosphatase as markers of bone turnover in hemodialysis patients. Plasma bone-specific alkaline phosphatase (bAP) has been demonstrated to be more reliable than total alkaline phosphatases (tAP) in providing information about bone turnover in patients with metabolic bone diseases. This study surveyed 42 hemodialysis patients who underwent a systematic transiliac bone biopsy for histomorphometry study. Plasma bAP was determined by using a new immunoassay (Tandem-R Ostase, Hybritech, Liège, Belgium). Plasma bAP values were compared with those of two other plasma markers of bone metabolism, namely tAP and intact parathyroid hormone (iPTH), for the correlations with bone histomorphometric parameters. Patients with high-turnover bone disease (HTBD) (N = 32) had significantly higher plasma bAP levels than patients with normal or low bone turnover (N/LTBD) (N = 10) (66.9 +/- 63.5 ng/mL versus 10.8 +/- 4.2 ng/mL, respectively). Bone formation and resorption were highly correlated in these patients, and plasma bAP levels were positively correlated with bone resorption parameters, including osteoclast surface (r = 0.39, P < 0.0001) and osteoclast number/mm2 (r = 0.36, P < 0.001), and with bone formation parameters, osteoblast surface (r = 0.50, P < 0.005), and bone formation rate (r = 0.91, P < 0.0001). The bone formation rate was better correlated with plasma bAP levels than with either plasma tAP or iPTH concentrations. Plasma bAP level equal or higher than 20 ng/mL, either alone or combined with plasma iPTH of 200 pg/mL, had the highest sensitivity, specificity, and predictability values for the diagnosis of high-turnover bone disease, and formally excluded patients with normal or LTBD. In conclusion, plasma bAP can be measured with a reliable immunoassay in hemodialysis patients. It represents a highly sensitive and specific biochemical marker of skeletal remodeling in these patients. Therefore, both serum iPTH and bAP are complementary in diagnoses of the type of renal osteodystrophy.


Toxic hazard and chemical analysis of leachates from furfurylated wood.
The furfurylation process is an extensively investigated wood modification process. Furfuryl alcohol molecules penetrate into the wood cell wall and polymerize in situ. This results in a permanent swelling of the wood cell walls. It is unclear whether or not chemical bonds exist between the furfuryl alcohol polymer and the wood. In the present study, five different wood species were used, both hardwoods and softwoods. They were treated with three different furfurylation procedures and leached according to three different leaching methods. The present study shows that, in general, the leachates from furfurylated wood have low toxicity. It also shows that the choice of leaching method is decisive for the outcome of the toxicity results. Earlier studies have shown that leachates from wood treated with furfuryl alcohol prepolymers have higher toxicity to Vibrio fischeri than leachates from wood treated with furfuryl alcohol monomers. This is probably attributable to differences in leaching of chemical compounds. The present study shows that this difference in the toxicity most likely cannot be attributed to maleic acid, furan, furfural, furfuryl alcohol, or 2-furoic acid. However, the difference might be caused by the two substances 5-hydroxymethylfurfural and 2,5-furandimethanol. The present study found no difference in the amount of leached furfuryl alcohol between leachates from furfurylated softwood and furfurylated hardwood species. Earlier studies have indicated differences in grafting of furfuryl alcohol to lignin. However, nothing was found in the present study that could support this. The leachates of furfurylated wood still need to be


Malt Beverage Brand Popularity Among Youth and Youth-Appealing Advertising Content.
This study examined whether alcohol brands more popular among youth are more likely to have aired television advertisements that violated the alcohol industry's voluntary code by including youth-appealing content. We obtained a complete list of 288 brand-specific beer advertisements broadcast during the National Collegiate Athletic Association (NCAA) men's and women's basketball tournaments from 1999 to 2008. All ads were rated by a panel of health professionals using a modified Delphi method to assess the presence of youth-appealing content in violation of the alcohol industry's voluntary code. The ads represented 23 alcohol brands. The popularity of these brands was operationalized as the brand-specific popularity of youth alcohol consumption in the past 30 days, as determined by a 2011 to 2012 national survey of underage drinkers. Brand-level popularity was used as the exposure variable to predict the odds of having advertisements with youth-appealing content violations. Accounting for other covariates and the clustering of advertisements within brands, increased brand popularity among underage youth was associated with significantly increased odds of having youth-appeal content violations in ads televised during the NCAA basketball tournament games (adjusted odds ratio = 1.70, 95% CI: 1.38, 2.09). Alcohol brands popular among underage drinkers are more likely to air television advertising that violates the industry's voluntary code which proscribes youth-appealing content.


Visible drug delivery by supramolecular nanocarriers directing to single-platformed diagnosis and therapy of pancreatic tumor model.
Nanoparticle therapeutics are promising platforms for cancer therapy. However, it remains a formidable challenge to assess their distribution and clinical efficacy for therapeutic applications. Here, by using multifunctional polymeric micellar nanocarriers incorporating clinically approved gadolinium (Gd)-based magnetic resonance imaging contrast agents and platinum (Pt) anticancer drugs through reversible metal chelation of Pt, simultaneous imaging and therapy of an orthotopic animal model of intractable human pancreatic tumor was successfully performed without any serious toxicity. The strong tumor contrast enhancement achieved by the micelles correlated with the 24 times increase of r(1) of the Gd chelates, the highest for the formulations using clinically approved Gd chelates reported to date. From the micro-synchrotron radiation X-ray fluorescence spectrometry scanning of the lesions, we confirmed that both the Gd chelates and Pt drugs delivered by the micelles selectively colocalized in the tumor interior. Our study provides new insights for the design of theranostic micelles with high contrast enhancement and site-specific clinical potential.


Prevalence and clinical significance of 15 autoantibodies in patients with new-onset systemic lupus erythematosus.
It is necessary to assay multiple autoantibodies simultaneously in the same group of new-onset systemic lupus erythematosus (SLE) patient. To determine the prevalence and clinical significance of 15 autoantibodies in patients with new-onset SLE. Twenty new-onset patients with SLE and 32 healthy individuals were enrolled in the present study. Serum levels of 15 autoantibodies were detected by enzyme linked immunosorbent assay. The clinical parameters of the patients were also recorded. The positive rate of anti-ssDNA was the highest (85%). The positive rates of anti-dsDNA, anti-ssDNA, AHA, anti-SSA, anti-SSB, anti-Sm, anti-U1RNP, AnuA, and rRNP were significantly higher in SLE patients than in nomal controls. In terms of clinical manifestation, there were significant associations of rRNP with photaesthesia and of AHA with nephritis. Clusters of autoantibodies were identified and associations of antibodies with symptoms were found in new-onset patients with SLE.


Effect of adding sitagliptin, a dipeptidyl peptidase-4 inhibitor, to metformin on 24-h glycaemic control and beta-cell function in patients with type 2 diabetes.
The aim of this study was to assess the effect of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on 24-h glucose control when added to the regimen of patients with type 2 diabetes who had inadequate glycaemic control on metformin therapy. In a double-blind, randomized, placebo-controlled, two-period crossover study, patients with type 2 diabetes with inadequate glycaemic control on metformin monotherapy (i.e. on a stable dose of > or = 1500 mg/day for > or = 6 weeks prior to the screening visit and an haemoglobin A(1c) (HbA(1c)) > or = 6.5% and <10% and fasting plasma glucose (FPG) < or = 240 mg/dl) were recruited for participation. A total of 28 patients (baseline HbA(1c) range = 6.5-9.6%) receiving metformin were randomized into one of two treatment sequences: the addition of placebo for 4 weeks followed by the addition of sitagliptin 50 mg twice daily (b.i.d.) for 4 weeks, or vice versa. At the end of each treatment period, patients were domiciled for frequent blood sampling over 24 h. The primary endpoint was 24-h weighted mean glucose (WMG) and secondary endpoints included change in FPG, mean of 7 daily self-blood glucose measurements (MDG) and fructosamine. beta-cell function was assessed from glucose and C-peptide concentrations were measured during the 5-h period after a standard breakfast meal by using the C-peptide minimal model. Despite a carryover effect from period 1 to period 2, the combined period 1 and period 2 results for glycaemic endpoints were statistically significant for sitagliptin relative to placebo when added to ongoing metformin therapy. To account for the carryover effect, the period 1 results were also compared between the groups. Following period 1, there were significant least-squares (LS) mean reductions in 24-h WMG of 32.8 mg/dl, significant LS mean reduction from baseline in MDG of 28 mg/dl, FPG of 20.3 mg/dl and fructosamine of 33.7 mmol/l in patients treated with sitagliptin relative to placebo (p < 0.05). When added to ongoing metformin therapy, parameters of beta-cell function were significantly improved with sitagliptin compared with placebo. No weight gain or increases in gastrointestinal adverse events or hypoglycaemia events were observed with sitagliptin relative to placebo during this study. In this study, the addition of sitagliptin 50 mg b.i.d. to ongoing metformin therapy improved 24-h glycaemic control and beta-cell function, and was generally well tolerated in patients with type 2 diabetes.


Homology-based enzymatic DNA fragment assembly-based illumina sequencing library preparation.
The current Illumina HiSeq and MiSeq platforms can generate paired-end reads of up to 2 x 250 bp and 2 x 300 bp in length, respectively. These read lengths may be substantially longer than genomic regions of interest when a DNA sequencing library is prepared through a target enrichment-based approach. A sequencing library preparation method has been developed based on the homology-based enzymatic DNA fragment assembly scheme to allow processing of multiple PCR products within a single read. Target sequences were amplified using locus-specific PCR primers with 8 bp tags, and using the tags, homology-based enzymatic DNA assembly was performed with DNA polymerase, T7 exonuclease and T4 DNA ligase. Short PCR amplicons can hence be assembled into a single molecule, along with sequencing adapters specific to the Illumina platforms. As a proof-of-concept experiment, short PCR amplicons (57-66 bp in length) derived from genomic DNA templates of field pea and containing variable nucleotide locations were assembled and sequenced on the MiSeq platform. The results were validated with other genotyping methods. When 5 PCR amplicons were assembled, 4.3 targeted sequences (single-nucleotide polymorphisms) on average were successfully identified within each read. The utility of this for sequencing of short fragments has consequently been demonstrated.


[Contemporary physiology of the menstrual cycle. Part II. The reproductive hormones, regulatory mechanisms and cyclical hormonal changes].
Knowledge of the biochemistry of the hormones that regulate the normal menstrual cycle provides the clinician with a tool that allows physiological management of the patient. The biochemistry of the gonadotrophins and their roles in the physiology of the normal menstrual cycle are briefly reviewed. The present state of knowledge of the regulatory mechanisms is discussed and the hormonal events during the normal menstrual cycle in 50 patients are presented.