Impact of peroral endoscopic myotomy on high-resolution manometry findings and their association with the procedure's outcomes.
Peroral endoscopic myotomy (POEM) is conducted for patients with esophageal motility disorders based on high-resolution manometry (HRM) findings. However, the impact of POEM on HRM findings and the associations between post-POEM HRM and outcomes have not been clarified. In a multicenter, observational, cohort study, patients with achalasia treated by POEM received follow-up HRM. Associations between patient characteristics, POEM procedures, and post-POEM HRM findings, including integrated relaxation pressure (IRP) and distal contractile integral (DCI), were investigated. Furthermore, POEM procedure outcomes were compared with post-POEM HRM findings. Of 2171 patients, 151 (7.0%) showed residual high post-POEM IRP (≥26 mm Hg; Starlet [Starmedical Ltd, Tokyo, Japan]). In a multivariate analysis, high pre-POEM IRPs (odds ratio [OR], 24.3) and gastric myotomy >2 cm (OR, .22) were found to be positive and negative predictive factors of high post-POEM IRPs, respectively. Peristalsis recovery (DCI ≥500 mm Hg/cm/s, at least 1 swallow; Starlet) was visible in 121 of 618 patients (19.6%) who had type II to III achalasia. High pre-POEM IRP (OR, 2.65) and DCI ≥500 (OR, 2.98) predicted peristalsis recovery, whereas esophageal dilation (OR, .42) predicted a risk of no recovery. Extended myotomy did not reveal a significant impact on peristalsis recovery. High or low post-POEM IRP and DCI did not increase the incidence of clinical failure, reflux esophagitis, or symptomatic GERD. Extended gastric myotomy decreased IRP values, whereas peristalsis recovery depended on the characteristics of achalasia. A residual high post-POEM IRP does not necessarily mean clinical failure. Routine HRM follow-up is not recommended after POEM.


Alternating selection for dispersal and multicellularity favors regulated life cycles.
The evolution of complex multicellularity opened paths to increased morphological diversity and organizational novelty. This transition involved three processes: cells remained attached to one another to form groups, cells within these groups differentiated to perform different tasks, and the groups evolved new reproductive strategies.1,2,3,4,5 Recent experiments identified selective pressures and mutations that can drive the emergence of simple multicellularity and cell differentiation,6,7,8,9,10,11 but the evolution of life cycles, particularly how simple multicellular forms reproduce, has been understudied. The selective pressure and mechanisms that produced a regular alternation between single cells and multicellular collectives are still unclear.12 To probe the factors regulating simple multicellular life cycles, we examined a collection of wild isolates of the budding yeast S. cerevisiae.12,13 We found that all these strains can exist as multicellular clusters, a phenotype that is controlled by the mating-type locus and strongly influenced by the nutritional environment. Inspired by this variation, we engineered inducible dispersal in a multicellular laboratory strain and demonstrated that a regulated life cycle has an advantage over constitutively single-celled or constitutively multicellular life cycles when the environment alternates between favoring intercellular cooperation (a low sucrose concentration) and dispersal (a patchy environment generated by emulsion). Our results suggest that the separation of mother and daughter cells is under selection in wild isolates and is regulated by their genetic composition and the environments they encounter and that alternating patterns of resource availability may have played a role in the evolution of life cycles.


Potential role for platelet apheresis for post-liver transplant thrombocytosis complicating portal vein thrombosis.
Except for patients with underlying myeloproliferative diseases (MPD), thrombocytosis is rarely encountered in cirrhotic patients after liver transplantation. Although the long-term control of primary thrombocytosis is important for the prevention of graft thrombosis in MPD patients, the threshold for intervention and best mode for the control of persistent reactive thrombocytosis after liver transplantation is unclear. We present two patients with extreme reactive thrombocytosis (over 1,000 x 10(9)/l) due to intra-abdominal sepsis after liver transplantation. Furthermore, both patients suffered from bleeding problems as well as ongoing venous thrombosis of the graft. Rapid control of the platelet count was achieved using platelet apheresis. The use of cell separation procedures may be a relatively rapid, reversible, and reasonably safe way to control platelet counts peri-operatively in liver transplant recipients.


Chemical synthesis of α(2,8) octasialosides, the minimum structure of polysialic acids.
Chemical synthesis of an α(2,8) octasialic acid by using an N-acetyl-5-N,4-O:7-O,9-O-dicarbonyl protected sialyl donor is reported. The glycosyl donor underwent α-selective sialylation at the C8 hydroxyl group to give α(2,8) sialyl oligomers. The resulting oligosaccharides were then deprotected to give the fully deprotected α(2,8) octasialic acid without lacking the N-acetyl groups.


Altitude, latitude and climate zone as determinants of mountain hare (Lepus timidus) coat colour change.
Local adaptation to annually changing environments has evolved in numerous species. Seasonal coat colour change is an adaptation that has evolved in multiple mammal and bird species occupying areas that experience seasonal snow cover. It has a critical impact on fitness as predation risk may increase when an individual is mismatched against its habitat's background colour. In this paper, we investigate the correlation between landscape covariates and moult timing in a native winter-adapted herbivore, the mountain hare (Lepus timidus), throughout Norway. Data was collected between 2011 and 2019 at 678 camera trap locations deployed across an environmental gradient. Based on this data, we created a Bayesian multinomial logistic regression model that quantified the correlations between landscape covariates and coat colour phenology and analysed among season and year moult timing variation. Our results demonstrate that mountain hare moult timing is strongly correlated with altitude and latitude with hares that live at higher latitudes and altitudes keeping their winter white coats for longer than their conspecifics that inhabit lower latitudes and altitudes. Moult timing was also weakly correlated with climate zone with hares that live in coastal climates keeping their winter white coats for longer than hares that live in continental climates. We found evidence of some among year moult timing variation in spring, but not in autumn. We conclude that mountain hare moult timing has adapted to local environmental conditions throughout Norway.


Dynamic involvement of ATG5 in cellular stress responses.
Autophagy maintains cell and tissue homeostasis through catabolic degradation. To better delineate the in vivo function for autophagy in adaptive responses to tissue injury, we examined the impact of compromised autophagy in mouse submandibular glands (SMGs) subjected to main excretory duct ligation. Blocking outflow from exocrine glands causes glandular atrophy by increased ductal pressure. Atg5(f/-);Aqp5-Cre mice with salivary acinar-specific knockout (KO) of autophagy essential gene Atg5 were generated. While duct ligation induced autophagy and the expression of inflammatory mediators, SMGs in Atg5(f/-);Aqp5-Cre mice, before ligation, already expressed higher levels of proinflammatory cytokine and Cdkn1a/p21 messages. Extended ligation period resulted in the caspase-3 activation and acinar cell death, which was delayed by Atg5 knockout. Moreover, expression of a set of senescence-associated secretory phenotype (SASP) factors was elevated in the post-ligated glands. Dysregulation of cell-cycle inhibitor CDKN1A/p21 and activation of senescence-associated β-galactosidase were detected in the stressed SMG duct cells. These senescence markers peaked at day 3 after ligation and partially resolved by day 7 in post-ligated SMGs of wild-type (WT) mice, but not in KO mice. The role of autophagy-related 5 (ATG5)-dependent autophagy in regulating the tempo, duration and magnitude of cellular stress responses in vivo was corroborated by in vitro studies using MEFs lacking ATG5 or autophagy-related 7 (ATG7) and autophagy inhibitors. Collectively, our results highlight the role of ATG5 in the dynamic regulation of ligation-induced cellular senescence and apoptosis, and suggest the involvement of autophagy resolution in salivary repair.


A systematic review of existing national priorities for child health research in sub-Saharan Africa.
We systematically reviewed existing national child health research priorities in Sub-Saharan Africa, and the processes used to determine them. Collaborators from a purposive sample of 20 WHO-AFRO Region countries, assisted by key informants from a range of governmental, non-governmental, research and funding organisations and universities, identified and located potentially eligible prioritisation documents. Included documents were those published between 1990 and 2002 from national or nationally accredited institutions describing national health research priorities for child health, alone or as part of a broader report in which children were a clearly identifiable group. Laboratory, clinical, public health and policy research were included. Two reviewers independently assessed eligibility for inclusion and extracted data. Eight of 33 potentially eligible reports were included. Five reports focused on limited areas of child health. The remaining three included child-specific categories in reports of general research priorities, with two such child-specific categories limited to reproductive health. In a secondary analysis of Essential National Health Research reports that included children, though not necessarily as an identifiable group, the reporting of priorities varied markedly in format and numbers of priorities listed, despite a standard recommended approach. Comparison and synthesis of reported priorities was not possible. Few systematically developed national research priorities for child health exist in sub-Saharan Africa. Children's interests may be distorted in prioritisation processes that combine all age groups. Future development of priorities requires a common reporting framework and specific consideration of childhood priorities.


Endometrial polyps in reproductive-age fertile and infertile women.
Endometrial polyps are a frequent finding in infertile patients. Little is known about the true prevalence of polyps in infertile patients. It is unproved whether polyps are causative of infertility, or whether surgical polypectomy by hysteroscopy improves the likelihood of successful conception. This article reviews endometrial polyps in reproductive-age fertile and infertile women.


In Vivo Dissection of Chamber-Selective Enhancers Reveals Estrogen-Related Receptor as a Regulator of Ventricular Cardiomyocyte Identity.
Cardiac chamber-selective transcriptional programs underpin the structural and functional differences between atrial and ventricular cardiomyocytes (aCMs and vCMs). The mechanisms responsible for these chamber-selective transcriptional programs remain largely undefined. We nominated candidate chamber-selective enhancers (CSEs) by determining the genome-wide occupancy of 7 key cardiac transcription factors (GATA4, MEF2A, MEF2C, NKX2-5, SRF, TBX5, TEAD1) and transcriptional coactivator P300 in atria and ventricles. Candidate enhancers were tested using an adeno-associated virus-mediated massively parallel reporter assay. Chromatin features of CSEs were evaluated by performing assay of transposase accessible chromatin sequencing and acetylation of histone H3 at lysine 27-HiChIP on aCMs and vCMs. CSE sequence requirements were determined by systematic tiling mutagenesis of 29 CSEs at 5 bp resolution. Estrogen-related receptor (ERR) function in cardiomyocytes was evaluated by Cre-loxP-mediated inactivation of ERRα and ERRγ in cardiomyocytes. We identified 134 066 and 97 506 regions reproducibly occupied by at least 1 transcription factor or P300, in atria or ventricles, respectively. Enhancer activities of 2639 regions bound by transcription factors or P300 were tested in aCMs and vCMs by adeno-associated virus-mediated massively parallel reporter assay. This identified 1092 active enhancers in aCMs or vCMs. Several overlapped loci associated with cardiovascular disease through genome-wide association studies, and 229 exhibited chamber-selective activity in aCMs or vCMs. Many CSEs exhibited differential chromatin accessibility between aCMs and vCMs, and CSEs were enriched for aCM- or vCM-selective acetylation of histone H3 at lysine 27-anchored loops. Tiling mutagenesis of 29 CSEs identified the binding motif of ERRα/γ as important for ventricular enhancer activity. The requirement of ERRα/γ to activate ventricular CSEs and promote vCM identity was confirmed by loss of the vCM gene profile in ERRα/γ knockout vCMs. We identified 229 CSEs that could be useful research tools or direct therapeutic gene expression. We showed that chamber-selective multi-transcription factor, P300 occupancy, open chromatin, and chromatin looping are predictive features of CSEs. We found that ERRα/γ are essential for maintenance of ventricular identity. Finally, our gene expression, epigenetic, 3-dimensional genome, and enhancer activity atlas provide key resources for future studies of chamber-selective gene regulation.


Is there a role for vitamin D in supporting cognitive function as we age?
Globally, an estimated 46 million people are currently living with dementia and this figure is projected to increase 3-fold by 2050, highlighting this major public health concern and its substantial associated healthcare costs. With pharmacological treatment yet to reach fruition, the emphasis on evidence-based preventative lifestyle strategies is becoming increasingly important and several modifiable lifestyle factors have been identified that may preserve cognitive health. These include good cardiovascular health, physical activity, low alcohol intake, smoking and a healthy diet, with growing interest in vitamin D. The aim of the present paper is to review the evidence supporting the potential roles of vitamin D in ageing and cognitive health in community-dwelling older adults. Furthermore, to describe the utility and challenges of cognitive assessments and outcomes when investigating vitamin D in this context. Evidence indicates that serum 25-hydroxyvitamin D (25(OH)D) may impact brain health. There is a biological plausibility from animal models that vitamin D may influence neurodegenerative disorders, through several mechanisms. Epidemiological evidence supports associations between low serum 25(OH)D concentrations and poorer cognitive performance in community-dwelling older populations, although an optimal 25(OH)D level for cognitive health could not be determined. The effect of raising 25(OH)D concentrations on cognitive function remains unclear, as there is a paucity of interventional evidence. At a minimum, it seems prudent to aim to prevent vitamin D deficiency in older adults, with other known common protective lifestyle factors, as a viable component of brain health strategies.


Long-acting antiretrovirals: a new era for the management and prevention of HIV infection.
The long-acting antiretroviral cabotegravir and rilpivirine combination has just received FDA, EMA and Health Canada approval. This novel drug delivery approach is about to revolutionize the therapy of people living with HIV, decreasing the 365 daily pill burden to only six intramuscular injections per year. In addition, islatravir, a first-in-class nucleoside reverse transcriptase translocation inhibitor, is intended to be formulated as an implant with a dosing interval of 1 year or more. At present, long-acting antiretroviral therapies (LA-ARTs) are given at fixed standard doses, irrespectively of the patient's weight and BMI, and without consideration for host genetic and non-genetic factors likely influencing their systemic disposition. Despite a few remaining challenges related to administration (e.g. pain, dedicated medical procedure), the development and implementation of LA-ARTs can overcome long-term adherence issues by improving patients' privacy and reducing social stigma associated with the daily oral intake of anti-HIV treatments. Yet, the current 'one-size-fits-all' approach does not account for the recognized significant inter-individual variability in LA-ART pharmacokinetics. Therapeutic drug monitoring (TDM), an important tool for precision medicine, may provide physicians with valuable information on actual drug exposure in patients, contributing to improve their management in real life. The present review aims to update the current state of knowledge on these novel promising LA-ARTs and discusses their implications, particularly from a clinical pharmacokinetics perspective, for the future management and prevention of HIV infection, issues of ongoing importance in the absence of curative treatment or an effective vaccine.


A Human-Centered Platform for HIV Infection Reduction in New York: Development and Usage Analysis of the Ending the Epidemic (ETE) Dashboard.
Dashboards have been increasingly used in clinic-based interventions, such as clinical performance improvement and monitoring risk of hospital readmissions, and are now gaining traction in population-based interventions, especially in disease assessment. We describe the design, development, and usage analysis of a geovisualization dashboard, the Ending the Epidemic (ETE) Dashboard. The ETE dashboard is a tool developed to track New York's progress towards achieving the goal of its ETE Initiative, to reduce new HIV infections from 3000 per year to 750 per year by the end of 2020. The ETE dashboard was adapted from an existing human-centered geovisualization platform, SanaViz, an Internet-enabled, interactive app incorporating principles of human-centered design and cognitive fit theory to enhance visual exploration of population health data. Usage evaluation of the ETE geovisualization dashboard was conducted using Google Analytics over a 4-week period from March 19 to April 18, 2016. The aim was to monitor user activity and analyze traffic on the ETE dashboard using evidence-based metrics that can provide adequate feedback to enhance its utilization. Usage was characterized based on three metrics: (1) number of unique visits to each page, (2) average time on each page in seconds, and (3) page bounce rate (ie, percentage of visits where user left the site immediately after viewing just a single page). Further analysis was also conducted by cross-tabulating specific usage metrics. Of 860 sessions, 324 sessions were initiated by unique users (37.7%). The most common acquisition channels included direct source (353/860, 41.0%); followed by referral traffic (340/860, 39.5%) and organic search (134/860, 15.5%). Usage statistics indicate that for the 860 sessions initiated by both new and returning users, the average viewing time was 8 minutes, 51 seconds, and the bounce rate was 46%. These statistics reflect positive results given that prior literature estimates an average session duration of 10-20 seconds and a bounce rate of 40-60% for most websites. Key findings from our study showed that the highest bounce rates were seen for the "About" page of the ETE website (65%), which describes the ETE initiative. The lowest bounce rates were seen for the ETE blog page (17%), consistent with prior research on website usage metrics that indicate that blog pages are often the most frequently viewed pages on Web portals. Our findings reveal the potential of Google Analytics as a tool to enhance user traffic and performance of the ETE geovisualization platform by using feedback from regular monitoring of key parameters including page bounce rates and average time on page. It also identifies the need for a follow-up usability assessment of the system.


Using baldrige performance excellence program approaches in the pursuit of radiation oncology quality care, patient satisfaction, and workforce commitment.
The Malcolm Baldrige National Quality Improvement Act was signed into law in 1987 to advance US business competitiveness and economic growth. Administered by the National Institute of Standards and Technology, the Act created the Baldrige National Quality Program, recently renamed the Baldrige Performance Excellence Program. The comprehensive analytical approaches referred to as the Baldrige Healthcare Criteria, are very well-suited for the evaluation and sustainable improvement of radiation oncology management and operations. A multidisciplinary self-assessment approach is used for radiotherapy program evaluation and development in order to generate a fact-based, knowledge-driven system for improving quality of care, increasing patient satisfaction, enhancing leadership effectiveness, building employee engagement, and boosting organizational innovation. This methodology also provides a valuable framework for benchmarking an individual radiation oncology practice's operations and results against guidelines defined by accreditation and professional organizations and regulatory agencies.


Vibration Control of Diamond Nanothreads by Lattice Defect Introduction for Application in Nanomechanical Sensors.
Carbon nanomaterials, such as carbon nanotubes (CNTs) and graphene sheets (GSs), have been adopted as resonators in vibration-based nanomechanical sensors because of their extremely high stiffness and small size. Diamond nanothreads (DNTs) are a new class of one-dimensional carbon nanomaterials with extraordinary physical and chemical properties. Their structures are similar to that of diamond in that they possess sp3-bonds formed by a covalent interaction between multiple benzene molecules. In this study, we focus on investigating the mechanical properties and vibration behaviors of DNTs with and without lattice defects and examine the influence of density and configuration of lattice defects on the two them in detail, using the molecular dynamics method and a continuum mechanics approach. We find that Young's modulus and the natural frequency can be controlled by alternating the density of the lattice defects. Furthermore, we investigate and explore the use of DNTs as resonators in nanosensors. It is shown that applying an additional extremely small mass or strain to all types of DNTs significantly changes their resonance frequencies. The results show that, similar to CNTs and GSs, DNTs have potential application as resonators in nano-mass and nano-strain sensors. In particular, the vibration behaviors of DNT resonators can be controlled by alternating the density of the lattice defects to achieve the best sensitivities.


Can individual health differences be explained by workplace characteristics?--A multilevel analysis.
Research on work-related health has mainly focused on individual factors. The present study expands the focus by exploring the role of organizational characteristics of workplaces for different individual health outcomes. The aim of the study was to look at differences in relative effect of workplace variations on five health outcomes, and to explain those differences in health outcomes by organizational characteristics. The sample encompassed 90 workplaces in Sweden and about 4300 individuals employed within these workplaces. Measurement of the workplace characteristics was carried out independently of the measurement of the individual's working conditions and health. Organizational data were collected by interviews with local managers at participating workplaces, and individual data were obtained by means of a survey of the employees. The results showed that a significant proportion of the variance in sickness absence, work ability, general health, and musculoskeletal disorders was attributed to the workplace. Of eight tested organizational characteristics, customer adaptation, lean production, and performance control could explain some of this workplace variance. The results also showed that only one organizational effect remained significant when controlled for the individual confounder of age and gender. High customer adaptation is associated with higher sickness absence. This association is not mediated via differences in mental and physical job strain.


Defensive practice among psychiatrists: a questionnaire survey.
There has been little research on the prevalence of defensive practice within hospital settings. The aim of this report was to examine the extent of defensiveness among psychiatrists and to examine the relationship between defensiveness and seniority, as well as the effect of previous experiences on the level of defensiveness. A postal questionnaire survey on defensive practice. Northern Region of England. 154 psychiatrists in the region. 96 responses were received from 48 equivalent consultants, 18 specialist registrars, and 23 equivalent senior house officers. Overall, 75% of those who replied had taken defensive actions within the past month. In particular, 21% had admitted patients overcautiously and 29% had placed patients on higher levels of observations. Junior psychiatrists were particularly prone to practise defensively. Important contributing factors included previous experience of complaints (against colleague or self), critical incidents, and legal claims. Almost three quarters of the psychiatrists who responded had practised defensively within the past month. The higher propensity of junior trainees to practise defensively may be attributable to their lack of confidence and experience. Experience of complaints (colleague or self) and critical incidents were important factors for defensive practice. Better and more structured training might reduce the high level of defensive practice and the way complaints and investigations are handled should be improved to maintain a truly "no blame" environment conducive to learning from past experience.


Molecular mechanisms underlying regional variations of catecholamine-induced lipolysis in rat adipocytes.
The mechanisms underlying catecholamine control of lipolysis were studied in rat white adipocytes from epididymal, retroperitoneal, and subcutaneous fat depots. Sensitivity of subcutaneous adipocytes to selective beta 3-adrenoceptor agonists was lower than that of internal adipocytes. beta 3-Adrenoceptor mRNA levels were lower in subcutaneous adipocytes. A decreased beta 1/beta 2-adrenoceptor-mediated lipolysis was also observed in these adipocytes, and the number of beta 1/beta 2-adrenoceptors was lower than in the internal adipocytes. The number of alpha 2-adrenoceptors was higher in subcutaneous adipocytes without a marked difference in alpha 2-adrenoceptor-mediated antilipolysis between the depots. Subcutaneous adipocytes were also characterized by a lower maximal lipolytic response to drugs acting at different levels of the lipolytic cascade, suggesting differences at the postreceptor level. Lower hormone-sensitive lipase activity and mRNA levels in subcutaneous adipocytes were in agreement with the lipolysis data. These results suggest that the pattern of expression of the genes of the lipolytic pathway varies with the anatomic location of the fat depot.


Case Report: Penetrating Corneal Injury Under an Intact Laser-assisted in Situ Keratomileusis Flap.
As the prevalence of post-laser-assisted in situ keratomileusis (LASIK) patients rises, recognition of possible traumatic complications and their management in this population becomes increasingly relevant. Penetrating injuries and intraocular foreign bodies are possible in post-LASIK corneas despite an intact anterior corneal surface. However, with prompt recognition and treatment, excellent visual recovery can be achieved. The purpose of this study was to report an interesting case of a penetrating foreign body through an intact LASIK flap. A 48-year-old man presented to an outside provider with right eye pain after his eye was struck by a tree branch. His ocular history was notable for uncomplicated LASIK surgery 4 years before presentation. On initial examination, the patient was diagnosed as having a small corneal abrasion and hyphema. Despite appropriate therapy, his eye continued to subjectively and objectively worsen. Follow-up examination after the injury was notable for a new dense hypopyon. Because of concern for secondary infection, the patient was referred urgently for further evaluation. Upon referral, the patient was noted to have a dense, fibrinous mass located inferiorly in the anterior chamber. Although the cornea was edematous temporally with deep folds, the anterior corneal surface appeared intact without evidence of laceration or flap displacement. Concern for endophthalmitis prompted anterior chamber washout, where a large vegetative foreign body was recovered despite an intact anterior corneal surface and LASIK. Post-operative anterior-segment optical coherence tomography after resolution of the corneal edema confirmed the presence of a well-aligned penetrating tract through the posterior stromal bed underneath the LASIK flap. Epithelial ingrowth that developed within the post-operative period further affirmed the initial tract of the penetrating foreign body. This case illustrates a novel complication after trauma in a post-LASIK patient, describes possible management, and underscores the care that must be taken when assessing patients with a history of LASIK surgery.


Patellar resurfacing in total knee arthroplasty: a prospective, randomized trial.
The management of the patella in total knee arthroplasty is still problematic. We aimed to identify differences in the clinical outcome of total knee arthroplasty according to whether or not patellar resurfacing had been performed in a prospective, randomized study of 220 osteoarthritic knees. Two hundred and twenty total knee arthroplasties in 201 patients were randomly assigned to be performed with either resurfacing or retention of the patella, and the results were followed for a mean of forty-eight months (range, thirty-six to seventy-nine months) in a double-blind (both patient and clinical evaluator blinded), prospective study. Evaluation was performed annually by an independent observer and consisted of assessment with the Knee Society clinical rating system, specific evaluation of anterior knee pain, a stair-climbing test, and radiographic examination. Fifteen (12%) of the 128 knees without patellar resurfacing and nine (10%) of the ninety-two knees with patellar resurfacing underwent a revision or another type of reoperation related to the patellofemoral articulation. This difference was not significant (chi square with one degree of freedom = 0.206, p = 0.650). At the time of the latest follow-up, there was a significantly higher incidence of anterior pain (chi square with one degree of freedom = 5.757, p = 0.016) in the knees that had not had patellar resurfacing. Patients who underwent patellar resurfacing had superior clinical results in terms of anterior knee pain and stair descent. However, anterior knee pain still occurred in patients with patellar resurfacing, and nine (10%) of the ninety-two patients in that group underwent a revision or another type of reoperation involving the patellofemoral joint. Weight but not body mass index was associated with the development of anterior knee pain in the patients without patellar resurfacing, a finding that suggests that patellofemoral dysfunction may be a function of joint loading rather than obesity.


Cryptic community structure and metabolic interactions among the heritable facultative symbionts of the pea aphid.
Most insects harbour influential, yet non-essential heritable microbes in their hemocoel. Communities of these symbionts exhibit low diversity. But their frequent multi-species nature raises intriguing questions on roles for symbiont-symbiont synergies in host adaptation, and on the stability of the symbiont communities, themselves. In this study, we build on knowledge of species-defined symbiont community structure across US populations of the pea aphid, Acyrthosiphon pisum. Through extensive symbiont genotyping, we show that pea aphids' microbiomes can be more precisely defined at the symbiont strain level, with strain variability shaping five out of nine previously reported co-infection trends. Field data provide a mixture of evidence for synergistic fitness effects and symbiont hitchhiking, revealing causes and consequences of these co-infection trends. To test whether within-host metabolic interactions predict common versus rare strain-defined communities, we leveraged the high relatedness of our dominant, community-defined symbiont strains vs. 12 pea aphid-derived Gammaproteobacteria with sequenced genomes. Genomic inference, using metabolic complementarity indices, revealed high potential for cooperation among one pair of symbionts-Serratia symbiotica and Rickettsiella viridis. Applying the expansion network algorithm, through additional use of pea aphid and obligate Buchnera symbiont genomes, Serratia and Rickettsiella emerged as the only symbiont community requiring both parties to expand holobiont metabolism. Through their joint expansion of the biotin biosynthesis pathway, these symbionts may span missing gaps, creating a multi-party mutualism within their nutrient-limited, phloem-feeding hosts. Recent, complementary gene inactivation, within the biotin pathways of Serratia and Rickettsiella, raises further questions on the origins of mutualisms and host-symbiont interdependencies.


Some energy relations in a host-virus system.
It was found that DNP (2,4-dinitrophenol) will inhibit completely the propagation of influenza virus in chorioallantoic membrane. This reagent did not permanently alter those metabolic processes required for the synthesis of virus and at the concentrations employed demonstrated no virucidal effects. In minced preparations of chorioallantoic membrane DNP was shown to have a pronounced stimulatory effect upon ATPase (adenosinetriphosphatase). When DNP was used with intact tissues, an excellent correlation was found between the inhibition of viral propagation and the stimulation of respiration and release of phosphate. Concentrations of DNP which permitted a twofold increase in the endogenous respiration of intact membranes allowed little or no viral synthesis. It is concluded that the energy required for viral synthesis derives from the oxidative phosphorylative activity of the host tissue.


Graphical classification of DNA sequences of HLA alleles by deep learning.
Alleles of human leukocyte antigen (HLA)-A DNAs are classified and expressed graphically by using artificial intelligence "Deep Learning (Stacked autoencoder)". Nucleotide sequence data corresponding to the length of 822 bp, collected from the Immuno Polymorphism Database, were compressed to 2-dimensional representation and were plotted. Profiles of the two-dimensional plots indicate that the alleles can be classified as clusters are formed. The two-dimensional plot of HLA-A DNAs gives a clear outlook for characterizing the various alleles.


Management of young femoral neck fractures: is there a consensus?
Femoral neck fractures in young adults (ages <60) are high-energy injuries that are associated with major fracture healing complications such as avascular necrosis, nonunion, and significant shortening. Historically, evidence from small trials has suggested multiple cannulated screws were the optimal implant; however, newer studies and implant designs warrant reevaluation of screws as the gold standard among surgeons. In addition, controversies surrounding reduction technique and urgency of surgical fixation have been previously identified. We aimed to survey surgeon treatment preferences for these challenging fractures. A 17-item survey was developed and tested for validity and reliability prior to administration. The questionnaire characterised surgeon demographics, treatment preferences for displaced and undisplaced fractures, and controversies for future clinical trials. The target population consisted of surgeons from the Canadian Orthopaedic Association, the Orthopaedic Trauma Association, and attendees at an international fracture course. 540 surgeons completed the survey, exceeding our sample size requirement. There was a similar proportion of respondents from academic and community hospitals. Most surgeons (61%) treat 1-5 young adult femoral neck fractures per year. For undisplaced fractures, 78% of respondents prefer to use multiple cannulated screws. For displaced fractures, equal preference for multiple screws (46%) and the sliding hip screw (SHS, 49%) was reported. The majority of surgeons perform an open reduction in less than 25% of cases, and the time to fixation was typically between 8 and 24h. Multiple cannulated screws remain the preferred treatment for most surgeons treating undisplaced fractures; however, there is an equal divide in preference between multiple screws and the SHS for displaced fractures. This increased preference for the SHS contradicts previous survey and small trial data recommending multiple screws for all fracture patterns. The lack of surgeon consensus and the high rates of fracture complications associated with fixation of young femoral neck fractures supports the need for definitive clinical trials to optimise patient important outcomes.


Change in mutagenicity in white rice after accelerated and long-term storage.
Certain reactions that occur in food during storage, such as nonenzymatic browning and lipid oxidation, form compounds that have been shown to be mutagenic. It is possible that over long storage periods, significant amounts of these products could be formed. Although some research has been published concerning the mutagenicity of foods due to processing or cooking, little research has been done regarding mutagenicity of foods stored for an extended time. The objective of this research was to determine the potential mutagenicity of white rice held in accelerated and long-term storage using the Ames Salmonella/microsome assay. Fresh long-grain white rice was packaged in foil laminate pouches and held at 60 degrees C for 18 wk. Rice stored for > 25 y in an oxygen-free environment at or below room temperature in size number 10 cans was obtained from residential storage. The standard plate-incorporation method was used to evaluate the mutagenic potential of all treatments using Salmonella typhimurium tester strains TA97a, TA98, TA100, and TA102. Samples were plated at 5 dilutions with and without rat liver S9 enzyme. A solvent control was also plated for each strain. Treatments yielding counts at least double the solvent control level were considered mutagenic. Plate counts for all treatments fell well below the required doubling of the solvent control value. White rice held in accelerated and long-term storage appears not to increase in mutagenic compounds as measured by the Ames assay, supporting its use for long-term storage purposes such as emergency preparedness and humanitarian food aid.


Hb J-Cordoba [alpha 2A beta 2(95)(FG2)Lys----Met]. A new Hb variant found in Argentina.
Hb J-Cordoba [alpha 2A beta 2(95)(FG2)Lys----Met], is one of the few hemoglobin variants discovered in Argentina. The structure and functional abnormalities are described. Hb J-Cordoba exhibits a slightly increased oxygen affinity, low cooperativity, and normal interaction with heterotropic cofactors.


Characteristics of magnetically separated rat tracheal epithelial cell populations.
A simple magnetic separation technique has been developed using lectins specific for two of the cell types found in the tracheal mucosa. The resulting populations of basal and secretory cells were examined for proliferative capacity in culture and in vivo. The basal cell fraction contains the cells that proliferate in culture and respond to 12-O-tetradecanoylphorbol-13-acetate. In addition, the basal cell fraction exhibited the highest proliferative capacity in vivo during the first few days after transplantation. Repopulation of inverted intestinal segments showed that only with suspensions containing a significant proportion of basal cells could a mucociliary lining be established. Segments receiving the same number of unsorted or predominantly mucous secreting cells did not repopulate in vivo. These data support the hypothesis that the basal cell is most likely the stem cell of the tracheal epithelium.


Distinct neuroblastoma-associated alterations of PHOX2B impair sympathetic neuronal differentiation in zebrafish models.
Heterozygous germline mutations and deletions in PHOX2B, a key regulator of autonomic neuron development, predispose to neuroblastoma, a tumor of the peripheral sympathetic nervous system. To gain insight into the oncogenic mechanisms engaged by these changes, we used zebrafish models to study the functional consequences of aberrant PHOX2B expression in the cells of the developing sympathetic nervous system. Allelic deficiency, modeled by phox2b morpholino knockdown, led to a decrease in the terminal differentiation markers th and dbh in sympathetic ganglion cells. The same effect was seen on overexpression of two distinct neuroblastoma-associated frameshift mutations, 676delG and K155X - but not the R100L missense mutation - in the presence of endogenous Phox2b, pointing to their dominant-negative effects. We demonstrate that Phox2b is capable of regulating itself as well as ascl1, and that phox2b deficiency uncouples this autoregulatory mechanism, leading to inhibition of sympathetic neuron differentiation. This effect on terminal differentiation is associated with an increased number of phox2b(+), ascl1(+), elavl3(-) cells that respond poorly to retinoic acid. These findings suggest that a reduced dosage of PHOX2B during development, through either a heterozygous deletion or dominant-negative mutation, imposes a block in the differentiation of sympathetic neuronal precursors, resulting in a cell population that is likely to be susceptible to secondary transforming events.


Electrochemical Molecular Imprinted Sensors Based on Electrospun Nanofiber and Determination of Ascorbic Acid.
In this study, electrochemical molecularly imprinted sensors were fabricated and used for the determination of ascorbic acid (AA). Nanofiber membranes of cellulose acetate (CA)/multi-walled carbon nanotubes (MWCNTs)/polyvinylpyrrolidone (PVP) (CA/MWCNTs/PVP) were prepared by electrospinning technique. After being transferred to a glass carbon electrode (GC), the nanofiber interface was further polymerized with pyrrole through electrochemical cyclic voltammetry (CV) technique. Meanwhile, target molecules (such as AA) were embedded into the polypyrrole through the hydrogen bond. The effects of monomer concentration (pyrrole), the number of scan cycles and scan rates of polymerization were optimized. Differential pulse voltammetry (DPV) tests indicated that the oxidation current of AA (the selected target) were higher than that of the structural analogues, which illustrated the selective recognition of AA by molecularly imprinted sensors. Simultaneously, the molecularly imprinted sensors had larger oxidation current of AA than non-imprinted sensors in the processes of rebinding. The electrochemical measurements showed that the molecularly imprinted sensors demonstrated good identification behavior for the detection of AA with a linear range of 10.0 - 1000 μM, a low detection limit down to 3 μM (S/N = 3), and a recovery rate range from 94.0 to 108.8%. Therefore, the electrochemical molecularly imprinted sensors can be used for the recognition and detection of AA without any time-consuming elution. The method presented here demonstrates the great potential for electrospun nanofibers and MWCNTs to construct electrochemical sensors.


The effect of biological DMARDs on the risk of congestive heart failure in rheumatoid arthritis: a systematic review.
A common cardiovascular manifestation in rheumatoid arthritis (RA) is congestive heart failure (CHF) in which inflammation is considered to play a pivotal role. Although anti-inflammatory therapy such as biological disease-modifying anti-rheumatic drugs (bDMARDs) have the potential of improving the cardiac function and reducing the risk of CHF, the published studies showed contrasting results. This review aims to systematically summarize and analyze literature regarding the effect of bDMARDs on the cardiac function and on the risk of CHF in RA. Observational cohort, randomized controlled trials and case-controlled studies were included. The systematic literature search was conducted in PubMed, Wiley/Embase, Cochrane, Web of Science and clinicaltrials.gov (up to 2017). Two authors assessed abstracts for inclusion and methodological quality was assessed by one reviewer. RA patients have a clinically relevant increased risk of developing CHF needing further attention. However, we found a lack of high quality studies. Future studies should focus on distinguishing the effect of myocardial inflammation reduction versus antibody-specific myocardial cellular effects of bDMARDs to improve the understanding of the effects of bDMARDs in RA patients and the relation with the development of CHF.


A DRB (5,6 dichloro-beta-D-ribofuranosylbenzimidazole)-resistant adenovirus mRNA.
5,6-Dichloro-beta-D ribofuranosyl benzimidazole (DRB) inhibits transcription from the major late adenovirus promoter, located on the r-strand at map position 16.3 on the viral genome. 100-500 nucleotides long RNA chains with capped 5'-termini are transcribed from this promoter in the presence of 70 muM DRB. Synthesis of the mRNA for polypeptide IX which is unspliced and maps on the r-strand between positions 9.7 and 10.9 appears, however, to be DRB-resistant although it is transcribed by polymerase II and capped. Translatable mRNA for polypeptide IX is synthesized in the presence of DRB while the mRNAs for the other viral structural proteins are not synthesized. This differential DRB-inhibition of polymerase II transcription suggests either that short mRNAs may escape inhibition or that unspliced mRNAs are insensitive to the drug.


Clinical efficacy and safety of successful longterm urate lowering with febuxostat or allopurinol in subjects with gout.
To determine longterm urate-lowering efficacy and clinical benefits and safety of therapy with febuxostat or allopurinol in subjects with gout. Subjects (n=1086) in this open-label extension study were assigned to fixed-dose daily urate-lowering treatment (ULT) with febuxostat (80 mg or 120 mg) or allopurinol (300 mg). ULT reassignment was permitted during months 1 to 6 to achieve serum urate (SUA) concentrations between 3.0 and <6.0 mg/dl. Flares requiring treatment, tophus size, safety, and SUA levels were monitored during up to 40 months of ULT maintenance. After 1 month initial treatment, >80% of subjects receiving either febuxostat dose, but only 46% of subjects receiving allopurinol, achieved SUA<6.0 mg/dl. After ULT reassignment, >80% of all remaining subjects maintained the primary efficacy endpoint of SUA<6.0 mg/dl at each visit. More subjects initially randomized to allopurinol required ULT reassignment to achieve SUA<6.0 mg/dl compared with subjects receiving febuxostat. Maintenance of SUA<6.0 mg/dl resulted in progressive reduction to nearly 0 in proportion of subjects requiring gout flare treatment. Baseline tophus resolution was achieved by 46%, 36%, and 29% of subjects maintained on febuxostat 80 mg, febuxostat 120 mg, and allopurinol, respectively. Overall adverse event rates (including cardiovascular adverse event rates), adjusted for 10-fold greater febuxostat than allopurinol exposure, did not differ significantly among treatment groups. Durable maintenance of goal range SUA level with either dose of febuxostat or in smaller numbers of subjects with allopurinol resulted in near elimination of gout flares and improved tophus status over time. Registered as NCT00175019.


A Data-Driven Approach to Identify the Predictors of Perceived Health Status Among Chinese and Korean Americans.
Asian Americans are the country's fastest-growing racial group, and several studies have focused on the health outcomes of Asian Americans, including perceived health status. Perceived health status provides a summarized view of the health of populations for diverse domains, such as the psychological, social, and behavioral aspects. Given its multifaceted nature, perceived health status should be carefully approached when examining any variables' influence because it results from interactions among many variables. A data-driven approach using machine learning provides an effective way to discover new insights when there are complex interactions among multiple variables. To date, there are not many studies available that use machine learning to examine the effects of diverse variables on the perceived health status of Chinese and Korean Americans. This study aims to develop and evaluate three prediction models using logistic regression, random forest, and support vector machines to find the predictors of perceived health status among Chinese and Korean Americans from survey data. The prediction models identified specific predictors of perceived health status. These predictors can be utilized when planning for effective interventions for the better health outcomes of Chinese and Korean Americans.


A Finite Element Study to Investigate the Mechanical Behaviour of Unidirectional Recycled Carbon Fibre/Glass Fibre-Reinforced Epoxy Composites.
Recycled carbon fibre-reinforced epoxy (rCF/EP) composites and recycled glass fibre-reinforced epoxy (rGF/EP) composites were numerically investigated to examine their mechanical properties, such as uniaxial tensile and impact resistance, using finite element (FE) methods. The recycled composites possess unidirectional, long and continuous fibre arrangements. A commercially available Abaqus/CAE software was used to perform an explicit non-linear analysis with a macroscale modelling approach, assuming the recycled composites as both homogenous and isotropic hardening. Five composite types were subjected to a numerical study based on the recycled fibre's volume fraction (40 and 60%) of rCF/EP and rGF/EP, along with (100%) fibreless cured epoxy samples. The materials were defined as elastoplastic with a continuum ductile damage (DUCTCRT) model. The experimental tensile test results were processed and calibrated as primary input data for the developed FE models. The numerical tensile results, maximum principal stress and logarithmic strain were validated with their respective experimental results. The stress-strain curves of both results possess a high accuracy, supporting the developed FE model. The numerical impact tests examined the von Mises stress distribution and found an exponential decrease in the stiffness of the composite types as their strength decreased, with the 60% rCF/EP sample being the stiffest. The model was sensitive to the mesh size, hammer velocity and simulation time step. Additionally, the total internal energy and plastic dissipation energy were measured, but were higher than the experimentally measured energies, as the FE models eliminated the defects from the recycled process, such as a poor fibre wettability to resin, fibre bundle formation in rCFs and char formation in rGFs. Overall, the developed FE models predicted the results for a defect-free rCF/EP and rGF/EP composite. Hence, the adopted modelling techniques can validate the experimental results of recycled composites with complex mechanical properties and damage behaviours in tensile and impact loading conditions.


Expression of engrailed in the developing brain and appendages of the onychophoran euperipatoides kanangrensis (Reid).
We have cloned an engrailed-class gene in the onychophoran Euperipatoides kanangrensis and investigated its expression using in situ hybridisation. The expression pattern was found to differ drastically from that previously described for another onychophoran species. In the present investigation, engrailed transcripts were detected in a subset of developing neurons in the brain anlage, and in the mesoderm as well as ectoderm of the developing limb buds. The engrailed positive cells of the brain are of differing developmental maturity, ranging from subepidermal neuronal precursors to neurons located basally in the embryo with developing axons. The lack of the traditional expression in the posterior compartment of segments reported earlier in onychophorans is discussed, and we suggest that onychophorans may have acquired two copies of engrailed with different functions.


Outcome of high-risk myelodysplastic syndrome after azacitidine treatment failure.
Azacitidine (AZA) is the current standard of care for high-risk (ie, International Prognostic Scoring System high or intermediate 2) myelodysplastic syndrome (MDS), but most patients will experience primary or secondary treatment failure. The outcome of these patients has not yet been described. Overall, 435 patients with high-risk MDS and former refractory anemia with excess blasts in transformation (RAEB-T) were evaluated for outcome after AZA failure. The cohort of patients included four data sets (ie, AZA001, J9950, and J0443 trials and the French compassionate use program). The median follow-up after AZA failure was 15 months. The median overall survival was 5.6 months, and the 2-year survival probability was 15%. Increasing age, male sex, high-risk cytogenetics, higher bone marrow blast count, and the absence of prior hematologic response to AZA were associated with significantly worse survival in multivariate analysis. Data on treatment administered after AZA failure were available for 270 patients. Allogeneic stem-cell transplantation and investigational agents were associated with a better outcome when compared with conventional clinical care. Outcome after AZA failure is poor. Our results should serve as a basis for designing second-line clinical trials in this population.


Drug delivery implants in the treatment of vitreous inflammation.
The eye is a model organ for the local delivery of therapeutics. This proves beneficial when treating vitreous inflammation and other ophthalmic pathologies. The chronicity of certain diseases, however, limits the effectiveness of locally administered drugs. To maintain such treatments often requires frequent office visits and can result in increased risk of infection and toxicity to the patient. This paper focuses on the implantable devices and particulate drug delivery systems that are currently being implemented and investigated to overcome these challenges. Implants currently on the market or undergoing clinical trials include those made of nonbiodegradable polymers, containing ganciclovir, fluocinolone acetonide, triamcinolone acetonide, and ranibizumab, and biodegradable polymers, containing dexamethasone, triamcinolone acetonide, and ranibizumab. Investigational intravitreal implants and particulate drug delivery systems, such as nanoparticles, microparticles, and liposomes, are also explored in this review article.


Diagnostic Efficacy of Diffusion-weighted Imaging in Distinguishing Chronic Diffuse Sclerosing Osteomyelitis from Suppurative Osteomyelitis of the Mandible.
Chronic diffuse sclerosing osteomyelitis (CDSO) is a non-suppurative inflammatory bone disease diagnosed based on combined clinical, histopathological, and radiological findings. Accurate diagnosis is important since CDSO is more refractory to treatment than suppurative osteomyelitis. The purpose of this study was to determine the diagnostic efficacy of diffusion-weighted imaging (DWI) in the quantitative assessment of CDSO to distinguish it from acute suppurative osteomyelitis (ASO) and chronic suppurative osteomyelitis (CSO) of the mandible. Using a retrospective cohort study design, we analyzed MRI data of 6 patients with CDSO and 34 patients with ASO and CSO. The mean apparent diffusion coefficient (ADC) values of the three groups (CDSO, ASO, and CSO groups) were calculated, and differences were analyzed using Kruskal-Wallis and post-hoc Mann-Whitney tests with Bonferroni adjustments. We performed a receiver operating characteristic (ROC) curve analysis to evaluate the ability of the ADC to predict CDSO. P < 0.05 was considered statistically significant. The mean ADCs in the CDSO, ASO, and CSO groups were 1.22 ± 0.04 × 10-3 mm2/s, 1.28 ± 0.08 × 10-3 mm2/s, and 1.06 ± 0.09 × 10-3 mm2/s, respectively. Significant differences were observed between the ASO and CSO groups (P < 0.001) and CSO and CDSO groups (P < 0.01). However, there was no significant difference between the ASO and CDSO groups (P = 0.21). The ROC analysis revealed a cut-off ADC value of 1.19 for distinguishing the CSO group from the CDSO group. Sensitivity, specificity, accuracy, and area under the ROC curve were 1.0, 0.92, 0, 95, and 0.94, respectively. The results suggest that ADC may be useful in distinguishing CDSO from mandibular suppurative osteomyelitis.


Blood pressure-lowering effect of dietary (-)-epicatechin administration in L-NAME-treated rats is associated with restored nitric oxide levels.
Epidemiological and intervention studies have shown that the intake of certain chocolates or cocoa products decreases blood pressure (BP) in humans. (-)-Epicatechin is the most abundant flavanol present in cocoa seeds and its derived foods. This work investigates the effects of dietary (-)-epicatechin on BP in rats that received N(ω)-nitro-l-arginine methyl ester (L-NAME) for 4 days. (-)-Epicatechin administration prevented the 42mm Hg increase in BP associated with the inhibition of NO production in a dose-dependent manner (0.2-4.0g/kg diet). This BP effect was associated with a reduction in L-NAME-mediated increase in the indexes of oxidative stress (plasma TBARS and GSSG/GSH(2) ratio) and with a restoration of the NO concentration. At the vascular level, none of the treatments modified NOS expression, but (-)-epicatechin administration avoided the L-NAME-mediated decrease in eNOS activity and increase in both superoxide anion production and NOX subunit p47(phox) expression. In summary, (-)-epicatechin was able to prevent the increase in BP and in oxidative stress and restored NO bioavailability. The fact that (-)-epicatechin is present in several plants usually consumed by humans gives the possibility of developing diets rich in those plants or pharmacological strategies using that flavonoid to diminish BP in hypertensive subjects.


Krill Oil Supplementation Reduces Exacerbated Hepatic Steatosis Induced by Thermoneutral Housing in Mice with Diet-Induced Obesity.
Preclinical evidence suggests that n-3 fatty acids EPA and DHA (Omega-3) supplemented as phospholipids (PLs) may be more effective than triacylglycerols (TAGs) in reducing hepatic steatosis. To further test the ability of Omega-3 PLs to alleviate liver steatosis, we used a model of exacerbated non-alcoholic fatty liver disease based on high-fat feeding at thermoneutral temperature. Male C57BL/6N mice were fed for 24 weeks a lard-based diet given either alone (LHF) or supplemented with Omega-3 (30 mg/g diet) as PLs (krill oil; ω3PL) or TAGs (Epax 3000TG concentrate; ω3TG), which had a similar total content of EPA and DHA and their ratio. Substantial levels of TAG accumulation (~250 mg/g) but relatively low inflammation/fibrosis levels were achieved in the livers of control LHF mice. Liver steatosis was reduced by >40% in the ω3PL but not ω3TG group, and plasma ALT levels were markedly reduced (by 68%) in ω3PL mice as well. Krill oil administration also improved hepatic insulin sensitivity, and its effects were associated with high plasma adiponectin levels (150% of LHF mice) along with superior bioavailability of EPA, increased content of alkaloids stachydrine and trigonelline, suppression of lipogenic gene expression, and decreased diacylglycerol levels in the liver. This study reveals that in addition to Omega-3 PLs, other constituents of krill oil, such as alkaloids, may contribute to its strong antisteatotic effects in the liver.


Feeding manipulation elicits different proliferative responses in the gastrointestinal tract of suckling and weanling rats.
Food deprivation has been found to stimulate cell proliferation in the gastric mucosa of suckling rats, whereas the weanling period has been reported to be unresponsive in terms of proliferative activity. In the present study we analyze regional differences in the effect of milk or food deprivation on cell proliferation of the epithelia of the esophagus and of five segments of small intestine in suckling, weanling and newly weaned Wistar rats of both sexes. DNA synthesis was determined using tritiated thymidine to obtain labeling indices (LI); crypt depth and villus height were also determined. Milk deprivation decreased LI by 50% in the esophagus (from 15 to 8.35%) and small intestine (from 40 to 20%) of 14-day-old rats. In 18-day-old rats, milk and food deprivation decreased LI in the esophagus (from 13 to 5%) and in the distal segments of the small intestine (from 36-40 to 24-32%). In contrast, the LI of the epithelia of the esophagus (5%) and of all small intestine segments (around 30%) of 22-day-old rats were not modified by food deprivation. Crypt depth did not change after treatment (80 to 120 microns in 14- and 22-day-old rats, respectively). Villus height decreased in some small intestine segments of unfed 14- (from 400 to 300 microns) and 18-day-old rats (from 480 to 360 microns). The results show that, contrary to the stomach response, milk deprivation inhibited cell proliferation in the esophagus and small intestine of suckling rats, demonstrating the regional variability of each segment of the gastrointestinal tract in suckling rats. In newly weaned rats, food deprivation did not alter the proliferation of these epithelia, similarly to the stomach, indicating that weanling is a period marked by the insensitivity of gastrointestinal epithelia to dietary alterations.


Expression of the protooncogene bcl-2 in the prostate and its association with emergence of androgen-independent prostate cancer.
The significance of apoptosis in relation to the development and progression of prostate cancer remains largely undefined. bcl-2 is an oncogene that functions by overriding apoptosis. bcl-2 expression was localized to the basal epithelial cells in the normal human prostate with the use of immunohistochemistry. Androgen-dependent and androgen-independent prostate carcinomas were evaluated immunohistochemically for bcl-2 expression. bcl-2 was undetectable in 13 of 19 cases of androgen-dependent cancers. In contrast, androgen-independent cancers displayed diffuse, high levels of bcl-2 staining (P < 0.01). In rats, steady-state levels of bcl-2 mRNA, assessed by S1 assays, reached maximum levels 10 days following castration. Addition of exogenous testosterone with, or without, flutamide demonstrated that the increased bcl-2 mRNA resulted from androgen ablation. Our findings indicate that bcl-2 expression is augmented following androgen ablation and is correlated with the progression of prostate cancer from androgen dependence to androgen independence.


Wide Institutional Variability in the Treatment of Pediatric Critical Asthma: A Multicenter Retrospective Study.
Children with status asthmaticus refractory to first-line therapies of systemic corticosteroids and inhaled beta-agonists often receive additional treatments. Because there are no national guidelines on the use of asthma therapies in the PICU, we sought to evaluate institutional variability in the use of adjunctive asthma treatments and associations with length of stay (LOS) and PICU use. Multicenter retrospective cohort study. Administrative data from the Pediatric Health Information Systems (PHIS) database. All inpatients 2-18 years old were admitted to a PHIS hospital between 2013 and 2021 with a diagnostic code for asthma. None. This study included 213,506 inpatient encounters for asthma, of which 29,026 patient encounters included care in a PICU from 39 institutions. Among these PICU encounters, large variability was seen across institutions in both the number of adjunctive asthma therapies used per encounter (min: 0.6, median: 1.7, max: 2.5, p < 0.01) and types of adjunctive asthma therapies (aminophylline, ipratropium, magnesium, epinephrine, and terbutaline) used. The center-level median hospital LOS ranged from 1 (interquartile range [IQR]: 1, 3) to 4 (3, 6) days. Among all the 213,506 inpatient encounters for asthma, the range of asthma admissions that resulted in PICU admission varied between centers from 5.2% to 47.3%. The average number of adjunctive therapies used per institution was not significantly associated with hospital LOS (p = 0.81) nor the percentage of encounters with PICU admission (p = 0.47). Use of adjunctive therapies for status asthmaticus varies widely among large children's hospitals and was not associated with hospital LOS or the percentage of encounters with PICU admission. Wide variance presents an opportunity for standardizing care with evidence-based guidelines to optimize outcomes and decrease adverse treatment effects and hospital costs.


The contribution of Australian fathers in getting food on the table among families with young children.
To explore how fathers with young children contributed to healthy home food provisioning and the factors enabling or inhibiting their involvement in family food tasks. Cross-sectional study using purpose-designed online survey. The survey assessed the level of responsibilities and practices in family food tasks, food agency (Cooking and Food Provisioning Action Scale), and use of resources to support involvement in family food tasks. Data collection took place over 3 weeks in November-December 2020 when various COVID-19-related restrictions were in place. Descriptive and regression analyses were used to assess psychosocial factors influencing responsibilities in family food tasks and food agency. Online survey. Included in the analysis were 435 Australian fathers with children aged under 5 years. Between 75 and 77 % of fathers in this study reported having at least half of the responsibilities in meal planning, shopping, and cooking. Health was frequently considered when deciding what to eat, but few used nutrition or food labels when shopping, tried new recipes or modified recipes to make them healthier. Involvement in family food tasks was promoted by a higher food agency, but time spent in employment was a significant barrier to reported food agency and greater involvement in food tasks. There was a high interest in resources to support healthy home food provisioning. The findings suggest the need to consider father-specific strategies to overcome time barriers and opportunities to enhance their capabilities for healthy home food provisioning.


Methylation of humic Acid fractions.
A new three-step permethylation procedure for humic acid fractions has been developed. In the first step, carboxylic acid groups are methylated with diazomethane in dimethylformamide; in the second step, hydroxyl groups are methylated with methyl iodide and dimethyl sulfinyl carbanion in dimethylformamide; and in the third step, acidic groups hydrolyzed in the earlier steps are methylated with diazomethane. The resulting product is completely soluble in methylene chloride (a high degree of methylation has been achieved).


Gastric volvulus in adults in a tertiary care hospital Karachi, Pakistan: A case series.
Gastric volvulus is a rare surgical emergency which is rare in children and occasionally presents in adults. It results due to pathological malrotation of the stomach along its longitudinal or short axis. The condition, if not treated promptly, can result in increased morbidity and carries a high risk of death. Very few cases have been reported in literature regards this important clinical condition. Early decompression and repair of anatomical defects are the corner stone of its management. There is a dire need to develop guidelines and algorithms for management and treatment of this rare condition to improve patient outcome, prevent recurrence and facilitate early diagnosis by practicing physicians and surgeons. We report three such cases which presented to our setup in emergency along with a brief description of how they were successfully managed.


Osteogenic commitment and differentiation of human mesenchymal stem cells by low-intensity pulsed ultrasound stimulation.
Low-intensity pulsed ultrasound (LIPUS) as an adjuvant therapy in in vitro and in vivo bone engineering has proven to be extremely useful. The present study aimed at investigating the effect of 30 mW/cm2 LIPUS stimulation on commercially available human mesenchymal stem cells (hMSCs) cultured in basal or osteogenic medium at different experimental time points (7, 14, 21 days). The hypothesis was that LIPUS would improve the osteogenic differentiation of hMSC and guarantying the maintenance of osteogenic committed fraction, as demonstrated by cell vitality and proteomic analysis. LIPUS stimulation (a) regulated the balance between osteoblast commitment and differentiation by specific networks (activations of RhoA/ROCK signaling and upregulation of Ribosome constituent/Protein metabolic process, Glycolysis/Gluconeogenesis, RNA metabolic process/Splicing and Tubulins); (b) allowed the maintenance of a few percentage of osteoblast precursors (21 days CD73+/CD90+: 6%; OCT-3/4+/NANOG+/SOX2+: 10%); (c) induced the activation of osteogenic specific pathways shown by gene expression (early: ALPL, COL1A1, late: RUNX2, BGLAP, MAPK1/6) and related protein release (COL1a1, OPN, OC), in particular in the presence of osteogenic soluble factors able to mimic bone microenvironment. To summarize, LIPUS might be able to improve the osteogenic commitment of hMSCs in vitro, and, at the same time, enhance their osteogenic differentiation.


Genome analysis of the meat starter culture bacterium Staphylococcus carnosus TM300.
The Staphylococcus carnosus genome has the highest GC content of all sequenced staphylococcal genomes, with 34.6%, and therefore represents a species that is set apart from S. aureus, S. epidermidis, S. saprophyticus, and S. haemolyticus. With only 2.56 Mbp, the genome belongs to a family of smaller staphylococcal genomes, and the ori and ter regions are asymmetrically arranged with the replichores I (1.05 Mbp) and II (1.5 Mbp). The events leading up to this asymmetry probably occurred not that long ago in evolution, as there was not enough time to approach the natural tendency of a physical balance. Unlike the genomes of pathogenic species, the TM300 genome does not contain mobile elements such as plasmids, insertion sequences, transposons, or STAR elements; also, the number of repeat sequences is markedly decreased, suggesting a comparatively high stability of the genome. While most S. aureus genomes contain several prophages and genomic islands, the TM300 genome contains only one prophage, PhiTM300, and one genomic island, nuSCA1, which is characterized by a mosaic structure mainly composed of species-specific genes. Most of the metabolic core pathways are present in the genome. Some open reading frames are truncated, which reflects the nutrient-rich environment of the meat starter culture, making some functions dispensable. The genome is well equipped with all functions necessary for the starter culture, such as nitrate/nitrite reduction, various sugar degradation pathways, two catalases, and nine osmoprotection systems. The genome lacks most of the toxins typical of S. aureus as well as genes involved in biofilm formation, underscoring the nonpathogenic status.


Acute clinical and angiographic results with the new AVE Micro coronary stent in bailout management.
To determine the feasibility and safety of development of this new stent, we deployed 28 AVE Micro stents in 23 native coronary artery lesions in 20 patients who developed acute or threatened closure after balloon angioplasty (BA). Ten stents were deployed in the left anterior descending artery, 10 in the circumflex, and 8 in the right coronary artery. Luminal dimensions were measured using a computer-based quantitative coronary angiographic analysis system (CAAS II). Stent deployment was successful in 27 of 28 attempts (96%). In 1 patient with a threatened closure of the left anterior descending artery associated with proximal vessel tortuosity, attempted stent deployment was unsuccessful. The clinical course of the other 19 patients in whom stent deployment was successful was free of coronary reintervention, bypass surgery, and death. A myocardial infarction was observed in 2 patients (10%), in 1 of whom the stent was implanted within 24 hours after the onset of acute myocardial infarction, and in the other acute vessel occlusion was present for 58 minutes before stent implantation. No subacute occlusion was observed. Event-free survival at 30 days after stent implantation was 85% (17 of 20 patients). Minimal luminal diameter was 0.85 +/- 0.57 mm before and 1.19 +/- 0.66 mm after BA, 2.61 +/- 0.39 mm during balloon inflation, 3.26 +/- 0.46 mm during and 2.74 +/- 0.51 mm after stenting, 3.43 +/- 0.52 mm during balloon inflation after stenting (Swiss Kiss), and 2.85 +/- 0.48 mm after Swiss Kiss.(ABSTRACT TRUNCATED AT 250 WORDS)


Using cultural immersion as the platform for teaching Aboriginal and Torres Strait Islander health in an undergraduate medical curriculum.
In 2011 Bond University was looking for innovative ways to meet the professional standards and guidelines in Aboriginal and Torres Strait Islander health in its Bachelor of Medicine, Bachelor of Surgery (MBBS) curriculum. In 2012 Bond piloted a compulsory cultural immersion program for all first year students, which is now a usual part of the MBBS program. Three phases were included - establishing an Indigenous health group, determining the Aboriginal and Torres Strait Islander educational content based on the professional standards and developing nine educational sessions and resources - as well as significant administrative processes. The cultural immersion was piloted in 2012 with 92 first year medical students. Following refinements it was repeated in 2013 with 95 students and in 2014 with 94 students. A comprehensive evaluation process was undertaken that included a paper-based evaluation form using a five-point Likert scale, as well as a confidential talking circle evaluation. The response rate was 95.4% (n=271, pooled cohort). Data were entered separately into SPSS and annual reports were written to the Faculty. Descriptive statistics are reported alongside themed qualitative data. The three combined student evaluation results were extremely positive. Students (n=271) strongly agreed that the workshop was well organised (M=4.3), that the facilitators contributed very positively to their experience (M=4.3), and that they were very satisfied overall with the activity (M=4.2). They agreed that the eight overall objectives had been well met (M=3.9-4.3). The nine sessions were highly evaluated with mean ratings of between 3.9 and 4.8. The 'best thing' about the immersion identified by more than half of the students was overwhelmingly (n=140) the Storytelling session, followed by bonding with the cohort, the Torres Strait Islander session and learning more about culture. The item identified as needing most improvement was the food (n=87), followed by the accommodation (n=65). The use of immersion in the early part of a cultural awareness program for medical students provides an extremely valuable platform from which to launch more detailed information about the history of Aboriginal and Torres Strait Islander Australia and its impact on the current health status of Aboriginal and Torres Strait Islander Australians. Doing this in a safe, supportive cross-cultural environment with highly skilled facilitators is essential. Key to success is strong leadership, commitment and support from Faculty level, a structured educational program and educating all staff and students about its importance throughout the journey.


[A case of appendicular supplementary root with external root resorption].
The case of a lateral maxillary incisor with a supplementary root fractured by external root resorption, is presented. The role played for the periodontal disease is shown in the clinical and radiographic achievements, and their implications in the pulpal disease. Endodontic therapy was performed and the diagnosis confirmed in the specimen histological research.


Sources of the increased longitudinal relaxation rates observed in melanotic melanoma. An in vitro study of synthetic melanins.
Researchers have suggested that the increased longitudinal relaxation rates (1/T1) of solvent water protons often found in melanoma result either from the paramagnetism of stable free radicals occurring in melanin or from that of methemoglobin in nonacute hemorrhagic regions of the tumor. However, field-cycling relaxometry and model solutions of synthetic melanin produced data which show that free radicals in melanin do not contribute significantly to 1/T1; instead, aggregation of melanin into macromolecular particles and binding of biologically-common paramagnetic metal ions (ie Fe3+, Mn2+, and Cu2+) to melanin effectively do increase 1/T1. These data have been combined with published histochemical data on melanin-containing tissues, while disregarding any additional effect related to hemorrhage. The result indicates that in melanoma the expected contribution of melanin-bound Fe3+ to 1/T1, at typical imaging fields, predominates under estimated in vivo conditions; furthermore, the total contribution from all sources, specifically due to the presence of melanin, is sufficient to account for reported measurements of 1/T1 in melanoma. Comparing the latter results with published data on T1 relaxation in model solutions of methemoglobin suggests that co-existing regions of nonacute microhemorrhage also may contribute significantly to 1/T1 under certain conditions. Finally, the implications for 1/T2 of melanin occurring in vivo within discrete melanosomes is discussed.


Comparative Genomics of Peroxisome Biogenesis Proteins: Making Sense of the PEX Proteins.
PEX genes encode proteins involved in peroxisome biogenesis and proliferation. Using a comparative genomics approach, we clarify the evolutionary relationships between the 37 known PEX proteins in a representative set of eukaryotes, including all common model organisms, pathogenic unicellular eukaryotes and human. A large number of previously unknown PEX orthologs were identified. We analyzed all PEX proteins, their conservation and domain architecture and defined the core set of PEX proteins that is required to make a peroxisome. The molecular processes in peroxisome biogenesis in different organisms were put into context, showing that peroxisomes are not static organelles in eukaryotic evolution. Organisms that lack peroxisomes still contain a few PEX proteins, which probably play a role in alternative processes. Finally, the relationships between PEX proteins of two large families, the Pex11 and Pex23 families, were analyzed, thereby contributing to the understanding of their complicated and sometimes incorrect nomenclature. We provide an exhaustive overview of this important eukaryotic organelle.


Bond strengths of tooth-colored posts, effect of sealer, dentin adhesive, and root region.
To evaluate the effect of sealer, dentin bonding agent, and root region on the push-out bond strengths of three tooth colored posts. 24 extracted human single rooted maxillary central incisors and canines were endodontically-treated using gutta percha and Roth's 801 or AH26 sealer. Posts (Cosmopost, Fibrekor, or Parapost Fiber White) were placed using one of two adhesive systems (Parapost Cement Conditioner with Parapost Cement, or One-Step with Hi-X Post self-cure resin cement). The push-out test was performed on different sections of the root to measure bond strengths. Cosmopost showed significantly lower mean bond strengths than either Fibrekor or Parapost. Bond strengths of the posts in the crown section were significantly higher than those in any of the three root areas measured. Neither the eugenol-containing sealer nor the bonding agent type had any effect on bond strength. Post type and root region significantly affected bond strength while sealer type or bonding agent had no effect on bond strength.


DISC1 regulates the transport of the NUDEL/LIS1/14-3-3epsilon complex through kinesin-1.
Disrupted-In-Schizophrenia 1 (DISC1) is a candidate gene for susceptibility to schizophrenia. DISC1 is reported to interact with NudE-like (NUDEL), which forms a complex with lissencephaly-1 (LIS1) and 14-3-3epsilon. 14-3-3epsilon is involved in the proper localization of NUDEL and LIS1 in axons. Although the functional significance of this complex in neuronal development has been reported, the transport mechanism of the complex into axons and their functions in axon formation remain essentially unknown. Here we report that Kinesin-1, a motor protein of anterograde axonal transport, was identified as a novel DISC1-interacting molecule. DISC1 directly interacted with kinesin heavy chain of Kinesin-1. Kinesin-1 interacted with the NUDEL/LIS1/14-3-3epsilon complex through DISC1, and these molecules localized mainly at cell bodies and partially in the distal part of the axons. DISC1 partially colocalized with Kinesin family member 5A, NUDEL, LIS1, and 14-3-3epsilon in the growth cones. The knockdown of DISC1 by RNA interference or the dominant-negative form of DISC1 inhibited the accumulation of NUDEL, LIS1, and 14-3-3epsilon at the axons and axon elongation. The knockdown or the dominant-negative form of Kinesin-1 inhibited the accumulation of DISC1 at the axons and axon elongation. Furthermore, the knockdown of NUDEL or LIS1 inhibited axon elongation. Together, these results indicate that DISC1 regulates the localization of NUDEL/LIS1/14-3-3epsilon complex into the axons as a cargo receptor for axon elongation.


Hierarchical porous Fe/N doped carbon nanofibers as host materials for high sulfur loading Li-S batteries.
Improving the sulfur utilization and cycling stability especially under high sulfur loading (>2 mg cm-2) is challenging due to the poor conductivity of sulfur and high soluble nature of polysulfides. Herein, we develop novel self-supporting carbon nanofibers with hierarchical porous structures and Fe/N absorption/nucleation centers (Fe/N-HPCNF) as high performance sulfur hosts via a facile co-spinning method. The highly interior porous carbon fiber structure provides good electrolyte infiltration, stable conductive networks and sufficient surfaces for fast Li+/electron transport and sulfur redox while maintaining high sulfur area loading. In addition, the abundant Fe/N heteroatoms evenly dispersed in the fiber strongly restrain polysulfide diffusion through a chemisorption effect and meanwhile regulate homogeneous sulfur nucleation, enhancing the stability of cathodes. Consequently, S@Fe/N-HPCNF cathodes realize a high initial specific capacity of 1273 mA h g-1 (areal capacity: 4.5 mA h cm-2) and long cycle life over 500 cycles with a high sulfur loading of 3.5 mg cm-2. A stable capacity of 6.6 mA h cm-2 is achieved even under 9 mg cm-2 sulfur. What's more, a pouch cell prototype with an ultrahigh sulfur area density (54 mg cm-2) was assembled and successfully lighted 10 yellow light-emitting diodes (LED), demonstrating the convenient scale-up of our S@Fe/N-HPCNF cathodes.


Stabilization of source-separated human urine by chemical oxidation.
The inhibitory effect of ozone and hydrogen peroxide (HP) on urea hydrolysis in stored urine was investigated and compared. Ozone showed less effect on urea hydrolysis due to the complicated composition of urine (including a large amount of urease-producing bacteria) and bacteria regeneration. Ozone concentration and total heterotrophic bacteria analysis demonstrated that residual ozone concentration decreased by 43% within 15 hr from 13.50 to 7.72 mg/L in the one-time ozonation urine test, and finally completely decomposed within 4 days. In addition, bacteria regenerated quickly after ozone completely decomposed. However, HP showed a significant effect on inhibiting urea hydrolysis not only in stored urine but also in fecal-contaminated urine. The suitable doses of applied HP to inhibit urea hydrolysis in stored urine, concentrations of 0.5 and 1.0 g feces per liter of fecal-contaminated urine, were 0.03, 0.16 and 0.23 mol/L, respectively. The urea concentrations after 2 months stored were 7,145, 7,109 and 7,234 mg/L, respectively.


The NADPH oxidase pathway is dysregulated by the P2X7 receptor in the SOD1-G93A microglia model of amyotrophic lateral sclerosis.
Inflammation and oxidative stress are thought to play determinant roles in the pathogenesis of amyotrophic lateral sclerosis (ALS). Degenerating motor neurons produce signals that activate microglia to release reactive oxygen species (ROS) and proinflammatory cytokines, resulting in a vicious cycle of neurodegeneration. The ALS-causing mutant protein Cu(+)/Zn(+) superoxide dismutase SOD1-G93A directly enhances the activity of the main ROS-producing enzyme in microglia, NADPH oxidase 2 (NOX2), a well-known player in the pathogenesis of ALS. Considering that extracellular ATP through P2X7 receptor constitutes a neuron-to-microglia alarm signal implicated in ALS pathology, we used primary microglial cells derived from transgenic SOD1-G93A mice and SOD1-G93A mice lacking the P2X7 receptor to investigate the effects of both pharmacological induction and genetic ablation of receptor activity on the NOX2 pathway. We observed that, in SOD1-G93A microglia, the stimulation of P2X7 receptor by 2'-3'-O-(benzoyl-benzoyl) ATP enhanced NOX2 activity in terms of translocation of p67(phox) to the membrane and ROS production; this effect was totally dependent on Rac1. We also found that, following P2X7 receptor stimulation, the phosphorylation of ERK1/2 was augmented in ALS microglia, and there was a mutual dependency between the NOX2 and ERK1/2 pathways. All of these microglia-mediated damaging mechanisms were prevented by knocking out P2X7 receptor and by the use of specific antagonists. These findings suggest a noxious mechanism by which P2X7 receptor leads to enhanced oxidative stress in ALS microglia and identify the P2X7 receptor as a promising target for the development of therapeutic strategies to slow down the progression of ALS.


Tramadol inhibits the contractility of isolated caprine detrusor muscle.
The atypical opioid analgesic tramadol has been shown to provide beneficial clinical and urodynamic effects in patients with detrusor overactivity. The effect of tramadol on isolated detrusor muscle has not been studied. This study investigated the ability of tramadol to inhibit acetylcholine (ACh)-induced contractility of the isolated caprine (goat) detrusor muscle. The effect of three concentrations (30, 100 and 300 μm) of tramadol on 10 caprine detrusor strips contracted by the addition of 100, 200 or 400 μm ACh was studied. The sensitivity of tramadol-induced inhibition of ACh responses to treatment with the β-adrenoceptor antagonist propranolol (1 μm) and the opioid receptor antagonist naloxone (100 μm) was also studied. Tramadol caused a concentration-dependent inhibition of ACh-induced detrusor contraction that was reversed by raising the concentration of ACh. Propranolol, but not naloxone, reversed the tramadol-induced inhibition of contractions to ACh in the detrusor. These results suggest that tramadol inhibits ACh-induced contractility of the isolated detrusor. They also suggest that tramadol does so by an indirect anticholinergic mechanism involving the stimulation of β-adrenoceptors. Tramadol may be useful in managing clinical conditions requiring relaxation of the detrusor muscle. Although the concentrations of tramadol needed to relax the detrusor were relatively high, these could be clinically attained via intravesical administration.


Excited state non-adiabatic dynamics of N-methylpyrrole: A time-resolved photoelectron spectroscopy and quantum dynamics study.
The dynamics of N-methylpyrrole following excitation at wavelengths in the range 241.5-217.0 nm were studied using a combination of time-resolved photoelectron spectroscopy (TRPES), ab initio quantum dynamics calculations using the multi-layer multi-configurational time-dependent Hartree method, as well as high-level photoionization cross section calculations. Excitation at 241.5 and 236.2 nm results in population of the A2(πσ(∗)) state, in agreement with previous studies. Excitation at 217.0 nm prepares the previously neglected B1(π3py) Rydberg state, followed by prompt internal conversion to the A2(πσ(∗)) state. In contrast with the photoinduced dynamics of pyrrole, the lifetime of the wavepacket in the A2(πσ(∗)) state was found to vary with excitation wavelength, decreasing by one order of magnitude upon tuning from 241.5 nm to 236.2 nm and by more than three orders of magnitude when excited at 217.0 nm. The order of magnitude difference in lifetimes measured at the longer excitation wavelengths is attributed to vibrational excitation in the A2(πσ(∗)) state, facilitating wavepacket motion around the potential barrier in the N-CH3 dissociation coordinate.


Understanding the Effects of Coordination and Self-Assembly on an Emissive Phenothiazine.
The local environment surrounding luminophores can significantly influence their photophysical properties. Herein, we report the self-assembly of a highly emissive platinum(II)-based metallacage. In order to accommodate the connectivity of the platinum(II) building block used in the self-assembly process, the luminophore-containing building block adopts a highly twisted geometry relative to its free form, leading to the emergence of an emissive transition with a radiative rate constant an order of magnitude higher than that of the free luminophore. This increased rate constant is the primary driver for the 10-fold increase in quantum yield from 4.2% to 40%. Model complexes with platinum or methyl groups bound to the nitrogen were synthesized. These complexes had lower quantum yields (10% and non-emissive, respectively) due mainly to decreases in radiative rate constants. Computational studies were conducted and indicated that the excited state of the ensembles, as well as the model complexes, is a result of charge transfer to the pyridyl groups, in contrast to the free luminophore, which involves the diphenyl sulfone moiety. The differences in quantum yields can be explained by a twist in the chromophore upon coordination of platinum or methylation on the pyridyl group, leading to intersystem crossing to a triplet state. This state then becomes more emissive with the addition of platinum, which increases the radiative rate constant via the heavy atom effect. The formation of a metallacage also decreases the non-radiative rate constant by inhibiting the intramolecular motions of the incorporated luminophore.


Demixing and orientational ordering in mixtures of rectangular particles.
Using scaled-particle theory for binary mixtures of two-dimensional hard particles with orientational degrees of freedom, we analyze the stability of phases with orientational order and the demixing phase behavior of a variety of mixtures. Our study is focused on cases where at least one of the components consists of hard rectangles, or a particular case of these, hard squares. A pure fluid of hard rectangles has recently been shown to exhibit, aside from the usual uniaxial nematic phase, an additional oriented phase, called tetratic phase, possessing two directors, which is the analog of the biaxial or cubatic phases in three-dimensional fluids. There is evidence, based on computer simulation studies, that the tetratic phase might be stable with respect to phases with lower translational symmetry for rectangles with low aspect ratios. As hard rectangles are mixed, in increasing concentration, with other particles not possessing stable tetratic order by themselves, the tetratic phase is destabilized, via a first- or second-order phase transition, to uniaxial nematic or isotropic phases; for hard rectangles of low aspect ratio (hard squares, in particular), tetratic order persists in a relatively large range of volume fractions. The order of these transitions depends on the particle geometry and dimensions, and also on the thermodynamic conditions of the mixture. The second component of the mixture has been chosen to be hard disks or discorectangles, the geometry of which is different from that of rectangles, leading to packing frustration and demixing behavior, or simply rectangles of different aspect ratio but with the same particle area, or different particle area but with the same aspect ratio. These mixtures may be good candidates for observing thermodynamically stable tetratic phases in monolayers of hard particles. Finally, demixing between fluid (isotropic-tetratic or tetratic-tetratic) phases is seen to occur in mixtures of hard squares of different sizes when the size ratio is sufficiently large.


Impact of renal function on adverse bleeding events associated with dual antiplatelet therapy in patients with acute coronary syndrome.
It is believed, but not well established, that renal dysfunction increases the risk of adverse bleeding events associated with dual antiplatelet therapy (DAPT), especially in patients with acute coronary syndrome (ACS). The aim of this study is to estimate the impact of renal function on adverse bleeding events associated with DAPT in patients with ACS. A total of 1,264 ACS patients who received DAPT, clopidogrel (n = 530) or prasugrel (n = 734) in addition to aspirin, were assessed in a multicenter observational study. The relationship between renal function and bleeding event, defined as BARC 3 or 5, was determined using a marginal effect from the logit model and Royston-Parmar model. During an average 313.1 days of the observation period, defined as the duration of DAPT after admission until the implementation of a change in the regimen, bleeding events were observed in 7.4% of patients (n = 94). The estimated curves demonstrated that the probability of bleeding was positive correlated with renal dysfunction (6.0 to 8.6), regardless of the DAPT regimen used. This probability was consistently higher in clopidogrel (7.4 to 10.5) than in prasugrel (4.8 to 0.7). This trend was also shown in maintenance hemodialysis patients (6.7 vs. 10.3). Estimated cumulative incidences among individual stages of renal function were drawn. In conclusion, bleeding events increased with worsening renal function, and prasugrel is safer than clopidogrel as a component of DAPT throughout all levels of renal function, including hemodialysis patients after ACS.


Cost effectiveness of strategies to combat cardiovascular disease, diabetes, and tobacco use in sub-Saharan Africa and South East Asia: mathematical modelling study.
To determine the relative costs and health effects of interventions to combat cardiovascular disease, diabetes, and tobacco related disease in order to guide the allocation of resources in developing countries. Cost effectiveness analysis of 123 single or combined prevention and treatment strategies for cardiovascular disease, diabetes, and smoking by means of a lifetime population model. Two World Health Organization sub-regions of the world: countries in sub-Saharan Africa with very high adult and high child mortality (AfrE) and countries in South East Asia with high adult and high child mortality (SearD). Demographic and epidemiological data were taken from the WHO databases of mortality and global burden of disease. Estimates of intervention coverage, effectiveness, and resource needs were drawn from clinical trials, observational studies, and treatment guidelines. Unit costs were taken from the WHO-CHOICE (Choosing Interventions that are Cost-Effective) price database. Cost per disability adjusted life year (DALY) averted, expressed in international dollars ($Int) for the year 2005. Most of the interventions studied were considered highly cost effective, meaning they generate one healthy year of life at a cost of <$Int2000 (which is the gross domestic product per capita of the two regions considered here). Interventions that offer particularly good monetary value, and which could be considered for prioritised implementation or scale up, include demand reduction strategies of the Framework Convention for Tobacco Control (<$Int950 and <$Int200 per DALY averted in AfrE and SearD respectively); combination drug therapy for people with a >25% chance of experiencing a cardiovascular event over the next decade, either alone or together with specific multidrug regimens for the secondary prevention of post-acute ischaemic heart disease and stroke (<$Int150 and <$Int230 per DALY averted in AfrE and SearD respectively); and retinopathy screening and glycaemic control for patients with diabetes (<$Int2100 and <$Int950 per DALY averted in AfrE and SearD respectively). This comparative economic assessment has identified a set of population-wide and individual strategies for prevention and control of cardiovascular disease that are inexpensive and cost effective in low resource settings.