Structure of RsrI methyltransferase, a member of the N6-adenine beta class of DNA methyltransferases.
DNA methylation is important in cellular, developmental and disease processes, as well as in bacterial restriction-modification systems. Methylation of DNA at the amino groups of cytosine and adenine is a common mode of protection against restriction endonucleases afforded by the bacterial methyltransferases. The first structure of an N:6-adenine methyltransferase belonging to the beta class of bacterial methyltransferases is described here. The structure of M. RSR:I from Rhodobacter sphaeroides, which methylates the second adenine of the GAATTC sequence, was determined to 1.75 A resolution using X-ray crystallography. Like other methyltransferases, the enzyme contains the methylase fold and has well-defined substrate binding pockets. The catalytic core most closely resembles the PVU:II methyltransferase, a cytosine amino methyltransferase of the same beta group. The larger nucleotide binding pocket observed in M. RSR:I is expected because it methylates adenine. However, the most striking difference between the RSR:I methyltransferase and the other bacterial enzymes is the structure of the putative DNA target recognition domain, which is formed in part by two helices on an extended arm of the protein on the face of the enzyme opposite the active site. This observation suggests that a dramatic conformational change or oligomerization may take place during DNA binding and methylation.


Association between serum uric acid-to-high-density lipoprotein cholesterol ratio and insulin resistance in patients with type 2 diabetes mellitus.
Previous studies have shown that the serum uric acid-to-high-density lipoprotein cholesterol ratio (UHR) is related to metabolic syndrome. However, no existing study has examined the relationship between UHR and insulin resistance (IR). Therefore, this study aims to explore the association between the UHR and IR in patients with type 2 diabetes mellitus (T2DM). Patients with type 2 diabetes mellitus (1,532 males and 1,013 females) were enrolled. Insulin resistance was measured by homeostatic model assessment of insulin resistance (HOMA-IR) and was defined as HOMI-IR ≥ 2.69. Pearson correlation, multiple logistic regression, ROC analysis, and subgroup analysis were used to evaluate the association between UHR and IR. UHR was associated with HOMA-IR in patients with type 2 diabetes mellitus (pearson's correlation coefficient = 0.274 in males and 0.337 in females, P < 0.001). Multiple logistic regression analysis showed that UHR was significantly correlated with insulin resistance (OR = 1.06, 95%CI = 1.03-1.08 in males and OR = 1.11, 95%CI = 1.08-1.15 in females). The area under the ROC curve (AUC) of UHR (AUC = 0.665 for males and 0.717 for females, all P < 0.01) was the largest compared with that of UA and HDL-C in insulin resistance. Subgroup analysis showed that there was a more significantly positive correlation among subjects with BMI ≥ 24 kg/m2 , age < 60 years old, HbA1c < 7%, non-hypertension, or in female subjects. Elevated UHR is significantly correlated with insulin resistance, which can be used as an indicator of insulin resistance in patients with type 2 diabetes mellitus.


The effects of yoga on the attention and behavior of boys with Attention-Deficit/ hyperactivity Disorder (ADHD).
Boys diagnosed with ADHD by specialist pediatricians and stabilized on medication were randomly assigned to a 20-session yoga group (n = 11) or a control group (cooperative activities; n = 8). Boys were assessed pre- and post-intervention on the Conners' Parent and Teacher Rating Scales-Revised: Long (CPRS-R:L & CTRS-R:L; Conners, 1997), the Test of Variables of Attention (TOVA; Greenberg, Cormna, & Kindschi, 1997), and the Motion Logger Actigraph. Data were analyzed using one-way repeated measures analysis of variance (ANOVA). Significant improvements from pre-test to post-test were found for the yoga, but not for the control group on five subscales of the Conners' Parents Rating Scales (CPRS): Oppositional, Global Index Emotional Lability, Global Index Total, Global Index Restless/Impulsive and ADHD Index. Significant improvements from pre-test to post-test were found for the control group, but not the yoga group on three CPRS subscales: Hyperactivity, Anxious/Shy, and Social Problems. Both groups improved significantly on CPRS Perfectionism, DSM-IV Hyperactive/ Impulsive, and DSM-IV Total. For the yoga group, positive change from pre- to post-test on the Conners' Teacher Rating Scales (CTRS) was associated with the number of sessions attended on the DSM-IV Hyperactive-Impulsive subscale and with a trend on DSM-IV Inattentive subscale. Those in the yoga group who engaged in more home practice showed a significant improvement on TOVA Response Time Variability with a trend on the ADHD score, and greater improvements on the CTRS Global Emotional Lability subscale. Results from the Motion Logger Actigraph were inconclusive. Although these data do not provide strong support for the use of yoga for ADHD, partly because the study was under-powered, they do suggest that yoga may have merit as a complementary treatment for boys with ADHD already stabilized on medication, particularly for its evening effect when medication effects are absent. Yoga remains an investigational treatment, but this study supports further research into its possible uses for this population. These findings need to be replicated on larger groups with a more intensive supervised practice program.


Follow-up of coiled cerebral aneurysms at 3T: comparison of 3D time-of-flight MR angiography and contrast-enhanced MR angiography.
Our aim was to compare contrast-enhanced MR angiography (CE-MRA) and 3D time-of-flight (TOF) MRA at 3T for follow-up of coiled cerebral aneurysms. Fifty-two patients treated with Guglielmi detachable coils for 54 cerebral aneurysms were evaluated at 3T MRA. 3D TOF MRA (TR/TE = 23/3.5; SENSE factor = 2.5) and CE-MRA by using a 3D ultrafast gradient-echo sequence (TR/TE = 5.9/1.8; SENSE factor = 3) enhanced with 0.1-mmol/kg gadobenate dimeglumine were performed in the same session. Source images, 3D maximum intensity projection, 3D shaded surface display, and/or 3D volume-rendered reconstructions were evaluated in terms of aneurysm occlusion/patency and artifact presence. In terms of clinical classification, the 2 MRA sequences were equivalent for 53 of the 54 treated aneurysms: 21 were considered fully occluded, whereas 16 were considered to have a residual neck and 16 were considered residually patent at follow-up MRA. The remaining aneurysm appeared fully occluded at TOF MRA but had a residual patent neck at CE-MRA. Visualization of residual aneurysm patency was significantly (P = .001) better with CE-MRA compared with TOF MRA for 10 (31.3%) of the 32 treated aneurysms considered residually patent with both sequences. Coil artifacts were present in 5 cases at TOF MRA but in none at CE-MRA. No relationship was apparent between the visualization of patency and either the size of the aneurysm or the interval between embolization and follow-up. At follow-up MRA at 3T, unenhanced TOF and CE-MRA sequences are similarly effective at classifying coiled aneurysms as occluded or residually patent. However, CE-MRA is superior to TOF MRA for visualization of residual patency and is associated with fewer artifacts.


Refining the research infrastructure at community health centers.
Community health centers (CHC) often partner with academics to conduct community-based participatory research (CBPR). Because of their research expertise, academic partners are usually the principal investigators (PIs); however, moving the home base of research to the community can prove beneficial to the CHC and its community. The purpose of this paper was to discuss the lessons learned after conducting a CBPR project and to share identified solutions. A longitudinal perinatal risk reduction intervention study was conducted with primiparous Native Hawaiian women receiving prenatal care at a CHC. The intervention incorporated home visiting, social support, and lactation management. Primary lessons learned from this participatory process can be grouped into infrastructure, human resources, and recruitment. Sharing lessons learned can serve to expand a CHC's involvement in research, and provide a venue for discovering innovative and viable community and practice based approaches to solving health disparity challenges.


A Review on the Fate of Legacy and Alternative Antimicrobials and Their Metabolites during Wastewater and Sludge Treatment.
Antimicrobial compounds are used in a broad range of personal care, consumer and healthcare products and are frequently encountered in modern life. The use of these compounds is being reexamined as their safety, effectiveness and necessity are increasingly being questioned by regulators and consumers alike. Wastewater often contains significant amounts of these chemicals, much of which ends up being released into the environment as existing wastewater and sludge treatment processes are simply not designed to treat many of these contaminants. Furthermore, many biotic and abiotic processes during wastewater treatment can generate significant quantities of potentially toxic and persistent antimicrobial metabolites and byproducts, many of which may be even more concerning than their parent antimicrobials. This review article explores the occurrence and fate of two of the most common legacy antimicrobials, triclosan and triclocarban, their metabolites/byproducts during wastewater and sludge treatment and their potential impacts on the environment. This article also explores the fate and transformation of emerging alternative antimicrobials and addresses some of the growing concerns regarding these compounds. This is becoming increasingly important as consumers and regulators alike shift away from legacy antimicrobials to alternative chemicals which may have similar environmental and human health concerns.


Alteration of Intraligand Donor-Acceptor Interactions Through Torsional Connectivity in Substituted Re-dppz Complexes.
The ground- and excited-state properties of a series of [ReCl(CO)3(dppz)] complexes with substituted donor groups were investigated. Alteration of donor-acceptor communication through modulation of torsional angle and the number and nature of the donor substituents allowed the effects on the photophysical properties to be characterized though both computational and spectroscopic techniques, including time-dependent density functional theory and resonance Raman and time-resolved infrared spectroscopy. The ground-state optical properties show significant variation as a result of donor group modulation, with an increased angle between the donor and acceptor blue-shifting and depleting the intensity of the lowest-energy transition, which is consistently intraligand charge transfer (ILCT) in nature. However, across all complexes studied there was minimal perturbation to the excited-state properties and dynamics. Three excited states on the picosecond, nanosecond, and microsecond time scales were observed in all cases, corresponding to 1ILCT, 3ππ*, and 3ILCT, respectively.


The GSTP1 gene is a susceptibility gene for childhood asthma and the GSTM1 gene is a modifier of the GSTP1 gene.
Bronchial asthma is a chronic airway disorder characterized by bronchial inflammation. Oxidative stress is a key component of inflammation. Glutathione S-transferase P1 (GSTP1), the abundant isoform of glutathione S-transferases (GSTs) in lung epithelium, plays a key role in cellular protection against oxidative stress. Several studies have shown that the GSTP1 geneis involved in the pathogenesis of asthma and a gene-gene interaction may occur within the GST gene superfamily. We screened single-nucleotide polymorphisms (SNPs) at the GSTP1 locus and performed an association study in the Japanese population using two independent case-control groups (group 1: 391 pediatric patients with asthma, 462 adult patients with asthma, and 639 controls, and group 2: 115 pediatric patients with asthma and 184 controls). The effect of GSTM1 null/present genotype on the association between GSTP1 Ile105Val and asthma was also investigated. We identified 20 SNPs at this locus and found this region consisted of one linkage disequilibrium block represented by four SNPs (tag SNPs). The association between the Ile105Val polymorphism in the GSTP1 gene and childhood asthma was significant in both groups (p = 0.047 in group 1, and p = 0.021 in group 2). This association was only significant in patients with GSTM1-positive genotype in both groups (group 1: GSTM1 present p = 0.013 and GSTM1 null p = 0.925, and group 2: GSTM1 present p = 0.015 and GSTM1 null p = 0.362). These findings suggest that the GSTP1 gene is a childhood asthma susceptible gene, and the GSTM1 gene is a modifier gene of GSTP1 for the risk of childhood asthma in the Japanese population.


[Giant Left Atrium with Mitral Regurgitation in Williams Syndrome: Report of a Case].
A 43-year-old woman with a history of mitral regurgitation and Williams syndrome was admitted for the treatment of congestive heart failure. A computed tomography scan showed a giant left atrium. No other cardiac abnormalities were observed. She received mitral valve replacement with a mechanical valve prosthesis and underwent left atrium volume reduction with a suture technique and modified Maze procedure. After the operation, the cardiac rhythm returned to sinus rhythm and chest radiography showed normal cardiothoracic ratio. Congestive heart failure did not recur.


To the point: reviews in medical education-taking control of the hidden curriculum.
This article, the ninth in the "To the Point" series that is prepared by the Association of Professors of Gynecology and Obstetrics Undergraduate Medical Education Committee, discusses the role of the "hidden curriculum" in shaping the professional identity of doctors in training. The characteristics that distinguish the formal curriculum and hidden curriculum are defined. Specific examples of hidden curricula in clinical environments and the positive and negative impacts that may result are highlighted. Techniques to evaluate clinical training environments and to identify the hidden curriculum are provided and are followed by methods to promote its positive messages and lessen its negative ones.


Development and preliminary evaluation of a particulate matter emission factor model for European motor vehicles.
Although modeling of gaseous emissions from motor vehicles is now quite advanced, prediction of particulate emissions is still at an unsophisticated stage. Emission factors for gasoline vehicles are not reliably available, since gasoline vehicles are not included in the European Union (EU) emission test procedure. Regarding diesel vehicles, emission factors are available for different driving cycles but give little information about change of emissions with speed or engine load. We have developed size-specific speed-dependent emission factors for gasoline and diesel vehicles. Other vehicle-generated emission factors are also considered and the empirical equation for re-entrained road dust is modified to include humidity effects. A methodology is proposed to calculate modal (accelerating, cruising, or idling) emission factors. The emission factors cover particle size ranges up to 10 microns, either from published data or from user-defined size distributions. A particulate matter emission factor model (PMFAC), which incorporates virtually all the available information on particulate emissions for European motor vehicles, has been developed. PMFAC calculates the emission factors for five particle size ranges [i.e., total suspended particulates (TSP), PM10, PM5, PM2.5, and PM1] from both vehicle exhaust and nonexhaust emissions, such as tire wear, brake wear, and re-entrained road dust. The model can be used for an unlimited number of roads and lanes, and to calculate emission factors near an intersection in user-defined elements of the lane. PMFAC can be used for a variety of fleet structures. Hot emission factors at the user-defined speed can be calculated for individual vehicles, along with relative cold-to-hot emission factors. The model accounts for the proportions of distance driven with cold engines as a function of ambient temperature and road type (i.e., urban, rural, or motorway). A preliminary evaluation of PMFAC with an available dispersion model to predict the airborne concentration in the urban environment is presented. The trial was on the A6 trunk road where it passes through Loughborough, a medium-size town in the English East Midlands. This evaluation for TSP and PM10 was carried out for a range of traffic fleet compositions, speeds, and meteorological conditions. Given the limited basis of the evaluation, encouraging agreement was shown between predicted and measured concentrations.


Quantifying emergence and self-organisation of Enterobacter cloacae microbial communities.
From microbial communities to cancer cells, many such complex collectives embody emergent and self-organising behaviour. Such behaviour drives cells to develop composite features such as formation of aggregates or expression of specific genes as a result of cell-cell interactions within a cell population. Currently, we lack universal mathematical tools for analysing the collective behaviour of biological swarms. To address this, we propose a multifractal inspired framework to measure the degree of emergence and self-organisation from scarce spatial (geometric) data and apply it to investigate the evolution of the spatial arrangement of Enterobacter cloacae aggregates. In a plate of semi-solid media, Enterobacter cloacae form a spatially extended pattern of high cell density aggregates. These aggregates nucleate from the site of inoculation and radiate outward to fill the entire plate. Multifractal analysis was used to characterise these patterns and calculate dynamics changes in emergence and self-organisation within the bacterial population. In particular, experimental results suggest that the new aggregates align their location with respect to the old ones leading to a decrease in emergence and increase in self-organisation.


Ecological comparative analysis of parasite fauna of Rutilus rutilus L. and Coregonus albula L. from waters of the European part of the Arctic Ocean Province.
The differences between the parasite fauna of Rutilus rutilus L. and Coregonus albula L. are caused by the fact that the former host is more warm-requiring and the conditions in waters of the Arctic Ocean Province of the Circumpolar Subregion are less favourable to it. On the other hand, C. Albula, which is a northern species, lives here under optimal conditions. R. rutilus is bentophytophagous and C. albula planktophagous species, which results in the differences in species composition of their parasites. Also differences in the growth and seasonal and annual changes of their parasite fauna have been observed.


Correlation between dynamic heterogeneity and local structure in a room-temperature ionic liquid: a molecular dynamics study of [bmim][PF(6)].
The complex dynamics of a room-temperature ionic liquid, 1-n-butyl-3-methylimidazolium hexafluorophosphate ([bmim][PF(6)]), is studied using equilibrium classical molecular dynamics simulations in the temperature range of 250-450 K. The activation energies for the self-diffusion of ions are around 30-34 kJ mol(-1), with that of the anion a little higher than that for the cation. The electrical conductivity of the liquid is calculated and good agreement with experiments is obtained. Structural relaxation is studied through the decay of coherent (total density-density correlation) and incoherent (self part of density-density correlation) intermediate scattering functions over a range of temperatures and wave vectors relevant to the system. The relaxation data are used to identify and characterize two processes, alpha and beta. The dependence of the two relaxation times on temperature and wave vector is obtained. The dynamical heterogeneity of the ions determined through the non-Gaussian parameter indicates the motion of the cation to be more heterogeneous than that of the anion. The faster ones among the cations are coordinated to faster anions, while slower cations are surrounded predominantly by slower anions. Thus, the dynamical heterogeneity in this ionic liquid is shown to have structural signatures.


Prevalence of Trachoma in Northern Benin: Results from 11 Population-Based Prevalence Surveys Covering 26 Districts.
We sought to evaluate trachoma prevalence in all suspected-endemic areas of Benin. We conducted population-based surveys covering 26 districts grouped into 11 evaluation units (EUs), using a two-stage, systematic and random, cluster sampling design powered at EU level. In each EU, 23 villages were systematically selected with population proportional to size; 30 households were selected from each village using compact segment sampling. In selected households, we examined all consenting residents aged one year or above for trichiasis, trachomatous inflammation - follicular (TF), and trachomatous inflammation - intense. We calculated the EU-level backlog of trichiasis and delineated the ophthalmic workforce in each EU using local interviews and telephone surveys. At EU-level, the TF prevalence in 1-9-year-olds ranged from 1.9 to 24.0%, with four EUs (incorporating eight districts) demonstrating prevalences ≥5%. The prevalence of trichiasis in adults aged 15+ years ranged from 0.1 to 1.9%. In nine EUs (incorporating 19 districts), the trichiasis prevalence in adults was ≥0.2%. An estimated 11,457 people have trichiasis in an area served by eight ophthalmic clinical officers. In northern Benin, over 8000 people need surgery or other interventions for trichiasis to reach the trichiasis elimination threshold prevalence in each EU, and just over one million people need a combination of antibiotics, facial cleanliness and environmental improvement for the purposes of trachoma's elimination as a public health problem. The current distribution of ophthalmic clinical officers does not match surgical needs.


Case-control study of enteropathogens associated with childhood diarrhea in Dhaka, Bangladesh.
The International Centre for Diarrhoeal Disease Research, Bangladesh, is a major center for research into diarrheal diseases. The center treats more than 100,000 patients a year. To obtain useful information representative of all patients, a surveillance system in which a 4% systematic sample of all patients is studied in detail, including etiological agents of diarrhea, was installed in October 1979. The first paper on etiology for the surveillance patients was published in 1982, which identified a potential enteric pathogen in 66% of patients. In subsequent years, several new agents of diarrhea have been identified. To assess the importance of a broader spectrum of diarrheal agents including the ones identified relatively recently, we studied 814 children with diarrhea. The children were up to 5 years of age and were part of the surveillance system. They were matched with an equal number of community controls without diarrhea. The study was conducted from February 1993 to June 1994. A potential enteric pathogen was isolated from 74.8% of diarrheal children and 43.9% of control children (P = 0.0001). Even though the first study was not a case-control study, it identified rotavirus, Campylobacter jejuni, enterotoxigenic Escherichia coli, Shigella spp. , and Vibrio cholerae O1 as major pathogens. The present study identified these pathogens as being significantly associated with diarrhea. In addition, the study also identified six additional agents, including enteropathogenic E. coli, Aeromonas spp., V. cholerae O139, enterotoxigenic Bacteroides fragilis, Clostridium difficile, and Cryptosporidium parvum, as being significantly associated with diarrhea. Plesiomonas shigelloides, Salmonella spp., diffusely adherent E. coli, enteroaggregative E. coli, Entamoeba histolytica, and Giardia lamblia were not significantly associated with diarrhea. Enteroinvasive E. coli, enterohemorrhagic E. coli, and Cyclospora cayetanensis were not detected in any of the children. The major burden of diseases due to most pathogens occurred in the first year of life. As in the previous study, seasonal patterns were seen for diarrhea associated with rotavirus, V. cholerae, and enterotoxigenic E. coli, and infections with multiple pathogens were common. With a few exceptions, these findings are in agreement with those from other developing countries. This knowledge of a broader spectrum of etiological agents of diarrhea in the surveillance patients will help us plan studies into various aspects of diarrheal diseases in this population.


Identifying the risk of disease progression after surgery for localized renal cell carcinoma.
To identify factors in a large cohort of patients with pathologically localized renal cell carcinoma (RCC) that predicted disease progression after surgery, as RCC most commonly presents as a localized tumour which is treated with surgical excision. Using an institutional database, we identified all patients who underwent radical or partial nephrectomy and had pathologically confirmed pT1 or pT2 RCC. Multivariable stepwise logistic regression analysis was used to calculate an odds ratio corresponding to the odds of progression to metastatic disease during surveillance, based on several clinical and pathological variables. We defined those variables that remained significant on multivariable analysis as risk factors and, based on the number of risk factors, we assessed risk of disease progression. In all, 925 patients were eligible for analysis with a median follow-up of 48.2 months. There was progression to metastatic disease in 53 (5.7%) patients; pT1 in 20/774 (2.6%), pT2 in 33/151 (21.9%). Risk factors included pT2 disease, male gender, symptoms at presentation (local or constitutional), presence of sarcomatoid de-differentiation, and macroscopic necrosis on final pathology. In 177 patients with no risk factors, none progressed; 20 of 618 (3.2%) with one or two risk factors had progression at a median of 37.1 months; 33 of 130 (25.4%) with three or more risk factors progressed at a median of 25.2 months. We identified five risk factors that can help to predict those patients with pT1 or pT2 RCC at highest risk for disease progression after surgery. The potential for disease progression is exceedingly low in patients with no risk factors and surveillance can be minimized in this group.


Mixed-norm regularization for brain decoding.
This work investigates the use of mixed-norm regularization for sensor selection in event-related potential (ERP) based brain-computer interfaces (BCI). The classification problem is cast as a discriminative optimization framework where sensor selection is induced through the use of mixed-norms. This framework is extended to the multitask learning situation where several similar classification tasks related to different subjects are learned simultaneously. In this case, multitask learning helps in leveraging data scarcity issue yielding to more robust classifiers. For this purpose, we have introduced a regularizer that induces both sensor selection and classifier similarities. The different regularization approaches are compared on three ERP datasets showing the interest of mixed-norm regularization in terms of sensor selection. The multitask approaches are evaluated when a small number of learning examples are available yielding to significant performance improvements especially for subjects performing poorly.


Genotyping for platelet-specific antigens: techniques for the detection of single nucleotide polymorphisms.
Accurate typing of patients for platelet-specific (human platelet) antigens (HPA) is required in several different clinical situations, and blood services need to maintain panels of HPA-typed apheresis platelet donors and whole-blood donors to support HPA alloimmunized patients. Six clinically relevant HPA alloantigen systems have been described and, in addition, a significant number of HPA alloantigens with a highly skewed allele frequency or of very low immunogenicity have been reported. Certain well-characterized biallelic systems such as Gov have not as yet been included in the HPA nomenclature but are included in this review. Biochemical studies have identified the platelet membrane proteins on which the HPA antigens are localized. Cloning of the genes encoding these proteins and the realization that there is adequate mRNA in fresh platelets has led to identification of the molecular basis of HPA antigens over the last decade. All but one of the biallelic platelet-specific alloantigen systems are based on a single nucleotide polymorphism in the DNA sequence, corresponding to a single amino acid substitution in the encoded primary protein sequence. The discovery of the genetic basis of the alloantigens has allowed the development of polymerase chain reaction-based techniques for HPA genotyping using genomic DNA. The genetic basis of the HPA alloantigens, the most commonly used genome typing techniques and their pitfalls, and future developments, are discussed in this review.


Symptoms indicating imminent breakage of a femoral interlocking nail: a case report.
Fractures of the femoral shaft treated with interlocking nails will ultimately result in breakage of the nail if the bone does not unite. Further management requires removal of the broken nail which may be a difficult process for the distal segment. If we can identify the symptoms just before the nail breaks, an exchange nailing becomes much easier. We present a patient with fibromatosis who underwent repeated surgery as well as radiotherapy at the age of 16. Six years later, she had a pathological fracture of the upper third of the femur for which an interlocking nail was inserted. The femur did not unite and the nail subsequently broke. Over a period of 12 years, three nails broke and had to be replaced. Two to 3 months before each breakage, the patient experienced the same set of symptoms for each episode. Knowing that her fracture was not going to heal will now alert us to do an exchange nailing before the nail broke again. It is well known that where there is evidence of non-union, pre-emptive treatment is necessary before implant failure. Femur nonunion, interlocking nail, symptoms before breakage of nail.


Differential effects of teriparatide on regional bone formation using (18)F-fluoride positron emission tomography.
Teriparatide increases skeletal mass, bone turnover markers, and bone strength, but local effects on bone tissue may vary between skeletal sites. We used positron emission tomography (PET) to study (18)F-fluoride plasma clearance (K(i)) at the spine and standardized uptake values (SUVs) at the spine, pelvis, total hip, and femoral shaft in 18 postmenopausal women with osteoporosis. Subjects underwent a 1-hour dynamic scan of the lumbar spine and a 10-minute static scan of the pelvis and femurs at baseline and after 6 months of treatment with 20 µg/day teriparatide. Blood samples were taken to derive the arterial input function and lumbar spine K(i) values evaluated using a three-compartment model. SUVs were calculated for the spine, pelvis, total hip, and femoral shaft. After 6 months treatment with teriparatide, spine K(i) values increased by 24% (p = .0003), while other model parameters were unchanged except for the fraction of tracer going to bone mineral (k(3)/[k(2) + k(3)]), which increased by 23% (p = .0006). In contrast to K(i) , spine SUVs increased by only 3% (p = .84). The discrepancy between changes in K(i) and SUVs was explained by a 20% decrease in (18)F(-) plasma concentration. SUVs increased by 37% at the femoral shaft (p = .0019), 20% at the total hip (p = .032), and 11% at the pelvis (p = .070). Changes in bone turnover markers and BMD were consistent with previous trials. We conclude that the changes in bone formation rate during teriparatide treatment as measured by (18)F(-) PET differ at different skeletal sites, with larger increases in cortical bone than at trabecular sites.


Nod2 suppresses Borrelia burgdorferi mediated murine Lyme arthritis and carditis through the induction of tolerance.
The internalization of Borrelia burgdorferi, the causative agent of Lyme disease, by phagocytes is essential for an effective activation of the immune response to this pathogen. The intracellular, cytosolic receptor Nod2 has been shown to play varying roles in either enhancing or attenuating inflammation in response to different infectious agents. We examined the role of Nod2 in responses to B. burgdorferi. In vitro stimulation of Nod2 deficient bone marrow derived macrophages (BMDM) resulted in decreased induction of multiple cytokines, interferons and interferon regulated genes compared with wild-type cells. However, B. burgdorferi infection of Nod2 deficient mice resulted in increased rather than decreased arthritis and carditis compared to control mice. We explored multiple potential mechanisms for the paradoxical response in in vivo versus in vitro systems and found that prolonged stimulation with a Nod2 ligand, muramyl dipeptide (MDP), resulted in tolerance to stimulation by B. burgdorferi. This tolerance was lost with stimulation of Nod2 deficient cells that cannot respond to MDP. Cytokine patterns in the tolerance model closely paralleled cytokine profiles in infected Nod2 deficient mice. We propose a model where Nod2 has an enhancing role in activating inflammation in early infection, but moderates inflammation after prolonged exposure to the organism through induction of tolerance.


Design of cell-matrix interactions in hyaluronic acid hydrogel scaffolds.
The design of hyaluronic acid (HA)-based hydrogel scaffolds to elicit highly controlled and tunable cell response and behavior is a major field of interest in developing tissue engineering and regenerative medicine applications. This review will begin with an overview of the biological context of HA, which is needed to better understand how to engineer cell-matrix interactions in the scaffolds via the incorporation of different types of signals in order to direct and control cell behavior. Specifically, recent methods of incorporating various bioactive, mechanical and spatial signals are reviewed, as well as novel HA modifications and crosslinking schemes with a focus on specificity.


[Human being and animals: different ontological and legal status].
The different legal status of human being and animals is a consequence of their different ontological status. Human being has dignity, which requires the recognition of rights that ensure a dignified life. The animal lacks dignity, but it must be protected by law, even though it does not have recognized rights. This study focuses on the ontological main differences between human being and animals, differences that nowadays can be tested empirically by the data provided by paleoanthropology. Human rights, based on dignity, are the guarantee that human being can develop exclusive capabilities to their way of being and that animals lack.


New Insights into the Genetic Basis of Monge's Disease and Adaptation to High-Altitude.
Human high-altitude (HA) adaptation or mal-adaptation is explored to understand the physiology, pathophysiology, and molecular mechanisms that underlie long-term exposure to hypoxia. Here, we report the results of an analysis of the largest whole-genome-sequencing of Chronic Mountain Sickness (CMS) and nonCMS individuals, identified candidate genes and functionally validated these candidates in a genetic model system (Drosophila). We used PreCIOSS algorithm that uses Haplotype Allele Frequency score to separate haplotypes carrying the favored allele from the noncarriers and accordingly, prioritize genes associated with the CMS or nonCMS phenotype. Haplotypes in eleven candidate regions, with SNPs mostly in nonexonic regions, were significantly different between CMS and nonCMS subjects. Closer examination of individual genes in these regions revealed the involvement of previously identified candidates (e.g., SENP1) and also unreported ones SGK3, COPS5, PRDM1, and IFT122 in CMS. Remarkably, in addition to genes like SENP1, SGK3, and COPS5 which are HIF-dependent, our study reveals for the first time HIF-independent gene PRDM1, indicating an involvement of wider, nonHIF pathways in HA adaptation. Finally, we observed that down-regulating orthologs of these genes in Drosophila significantly enhanced their hypoxia tolerance. Taken together, the PreCIOSS algorithm, applied on a large number of genomes, identifies the involvement of both new and previously reported genes in selection sweeps, highlighting the involvement of multiple hypoxia response systems. Since the overwhelming majority of SNPs are in nonexonic (and possibly regulatory) regions, we speculate that adaptation to HA necessitates greater genetic flexibility allowing for transcript variability in response to graded levels of hypoxia.


Dual signaling by the alpha(v)beta(3)-integrin activates cytosolic PLA(2) in bovine pulmonary artery endothelial cells.
Vitronectin, which ligates the alpha(v)beta(3)-integrin, increases both lung capillary permeability and lung endothelial Ca(2+). In stable monolayers of bovine pulmonary artery endothelial cells (BPAECs) viewed with confocal microscopy, multimeric vitronectin aggregated the apically located alpha(v)beta(3)-integrin. This caused arachidonate release that was inhibited by pretreating the monolayers with the anti-alpha(v)beta(3) monoclonal antibody (MAb) LM609. No inhibition occurred in the presence of the isotypic MAb PIF6, which recognizes the integrin alpha(v)beta(5). Vitronectin also caused membrane translocation and phosphorylation of cytosolic phospholipase A(2) (cPLA(2)) as well as tyrosine phosphorylation of the mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase (ERK) 2. The cPLA(2) inhibitor arachidonyl trifluoromethylketone, the tyrosine kinase inhibitor genistein, and the MAPK kinase inhibitor PD-98059 all blocked the induced arachidonate release. PD-98059 did not inhibit the increase of cytosolic Ca(2+) or cPLA(2) translocation, although it blocked tyrosine phosphorylation of ERK2. Moreover, although the intracellular Ca(2+) chelator MAPTAM also inhibited arachidonate release, it did not inhibit tyrosine phosphorylation of ERK2. These findings indicate that ligation of apical alpha(v)beta(3) in BPAECs caused ERK2 activation and an increase of intracellular Ca(2+), both conjointly required for cPLA(2) activation and arachidonate release. This is the first instance of a tyrosine phosphorylation-initiated "two-hit" signaling pathway that regulates an integrin-induced proinflammatory response.


Effect of free distribution of safety equipment on usage among motorcycle-taxi drivers in Tanzania--A cluster randomised controlled trial.
Deaths due to road traffic injuries, particularly motorcycle crashes, have increased rapidly in many African nations and context-specific strategies to improve preventative behaviours are needed. Although adhering to conspicuity measures by wearing reflective safety vests is a highly effective crash prevention strategy and mandated by law among motorcycle-taxi drivers in some African countries, actual use is currently low. We aimed to test whether eliminating cost-barriers through the provision of free reflective, fluorescent motorcycle safety vests would lead to increased utilisation among a high-risk population of motorcycle-taxi drivers in Tanzania. A cluster randomised controlled trial was conducted among 180 motorcycle-taxi drivers. Participants randomised to the intervention arm (90) received free, reflective, fluorescent vests; participants randomised to the control arm (90) did not receive free vests. Participants' use of reflective vests was then observed on city streets over a three month period and differential uptake was estimated using mixed-effects logistic regression. Baseline use of reflective vests was 3.3% in both arms. Seventy-nine drivers in the intervention arm and 82 drivers in the control arm were observed during follow-up. The average proportion of observations during which motorcycle drivers were using a reflective vest was 9.5% in the intervention arm, compared to 2.0% in the control arm (odds ratio: 5.5, 95% confidence interval: 1.1-26.9, p-value: 0.04). Although distribution of free reflective vests led to a statistically significant increase in vest usage, the absolute increase was modest. Additional strategies beyond removing economic barriers are important to augment adherence to road safety behaviours for injury prevention.


Positive regulation of Clostridium difficile toxins.
The toxigenic element of Clostridium difficile VPI 10463 contains a small open reading frame (ORF) immediately upstream of the toxin B gene (G. A. Hammond and J. L. Johnson, Microb. Pathog. 19:203-213, 1995). The deduced amino acid sequence of the ORF, which we have designated txeR, encodes a 22-kDa protein which contains a helix-turn-helix motif with sequence identity to DNA binding regulatory proteins. We used a DNA fragment containing the C. difficile toxin A repeating units (ARU) as a reporter gene to determine if txeR regulates expression from the toxin A and toxin B promoters in Escherichia coli. To test the affect of txeR on expression, we fused the ARU gene fragment in frame with the toxin promoters. The fusions expressed a 104-kDa protein that contained the epitopes for monoclonal antibody PCG-4, which we used to measure levels of recombinant ARU by enzyme-linked immunosorbent assay. When txeR was expressed in trans with the toxin B promoter-ARU fusion contained on separate low-copy-number plasmid, expression of ARU increased over 800-fold. Furthermore, when we tested the toxin A promoter fused to ARU, expression increased over 500-fold with txeR supplied in trans. Our results suggest that TxeR is a positive regulator that activates expression of the C. difficile toxins.


Partial replication of two rumination-related candidate gene studies.
Two recent papers associated candidate genes with brooding rumination, a possible cognitive endophenotype for depression, in children ages 8-14 years. Stone et al. reported that BDNF val66met polymorphism predicted brooding in adolescence. Woody et al. reported that children carrying at least one copy of a CRHR1 TAT haplotype reported less brooding than their peers in the presence of maternal depression. We attempted to replicate and extend these findings in a sample of twins aged 12-16 years. We analyzed the BDNF val66met (rs6265) polymorphism and two (rs242924 and rs7209436) out of three single nucleotide polymorphisms (SNPs) that Woody et al. used to create a CRHR1 haplotype. We controlled for maternal history of depression and clustering within families. Unlike Stone et al., we found higher brooding among BDNF Met carriers. This main effect was qualified by an interaction with pubertal status, with the effect driven by more physically mature participants. Similar to Woody et al., we found an interaction between CRHR1 SNPs and maternal depression, with the homozygous minor genotype acting as a protective factor against brooding in the presence of maternal depression. Findings provide partial support for the influence of candidate genes in two environmentally sensitive systems on brooding.


Effects of enucleation of the fixating eye on strabismic amblyopia in monkeys.
The effects of enucleation of the fixating eye on the visual function of the deviating eye were studied in two rhesus monkeys with strabismic amblyopia. An esotropia was surgically induced when the monkeys were approximately 1 mo of age, and the fixating eyes were then enucleated at age 3 yr 11 mo. Four measures of visual function (photopic increment-threshold spectral sensitivity, scotopic spectral sensitivity, spatial modulation sensitivity, and temporal modulation sensitivity) were determined for both eyes prior to enucleation and for the deviating eyes over an 11-month period following the surgical removal of the fixating eye. Both monkeys showed some recovery of contrast sensitivity of their deviating eyes. The extrapolated cut-off values for their spatial modulation sensitivity functions increased from .27 to 2.8 c/deg for one animal and from .28 to 6.3 c/deg for the other. The extrapolated cut-off frequencies for the temporal modulation sensitivity functions of both animals showed an increase of 20-25 Hz compared to the pre-enucleation values. The spectral sensitivity functions of one monkey recovered to near normal values following enucleation, while both the photopic and scotopic functions of the other animal remained at pre-enucleation levels. Overall, the results of the experiments indicate that the removal of the fixating eyes of monkeys with strabismic amblyopia can result in significant improvements in the functional capacity of their deviating eyes.


Custodial evaluations of Native American families: implications for forensic psychiatrists.
Native American children in the United States have been adopted by non-Indian families at rates that threaten the preservation of their Indian history, traditions, and culture. The Indian Child Welfare Act (ICWA), which established restrictive parameters that govern the placement of Native American children into foster care and adoptive homes, was ratified in an effort to keep American Indian families intact. This article addresses matters of importance to psychiatrists who conduct custody evaluations of Native American children and families. A summary of events that preceded enactment of the ICWA is given, along with guidelines for forensic psychiatrists who conduct foster and adoptive care evaluations of Native American children. We use clinical vignettes to illustrate how the ICWA informs the custody evaluation process as well as approaches to cultural concerns, including biases that forensic evaluators may encounter during these evaluations.


Mental Health Revisits at US Pediatric Emergency Departments.
Pediatric emergency department (ED) visits for mental health crises are increasing. Patients who frequently use the ED are of particular concern, as pediatric mental health ED visits are commonly repeat visits. Better understanding of trends and factors associated with mental health ED revisits is needed for optimal resource allocation and targeting of prevention efforts. To describe trends in pediatric mental health ED visits and revisits and to determine factors associated with revisits. In this cohort study, data were obtained from 38 US children's hospital EDs in the Pediatric Health Information System between October 1, 2015, and February 29, 2020. The cohort included patients aged 3 to 17 years with a mental health ED visit. Characteristics of patients, encounters, hospitals, and communities. The primary outcome was a mental health ED revisit within 6 months of the index visit. Trends were assessed using cosinor analysis and factors associated with time to revisit using mixed-effects Cox proportional hazards regression. There were 308 264 mental health ED visits from 217 865 unique patients, and 13.2% of patients had a mental health revisit within 6 months. Mental health visits increased by 8.0% annually (95% CI, 4.5%-11.4%), whereas all other ED visits increased by 1.5% annually (95% CI, 0.1%-2.9%). Factors associated with mental health ED revisits included psychiatric comorbidities, chemical restraint use, public insurance, higher area measures of child opportunity, and presence of an inpatient psychiatric unit at the presenting hospital. Patients with psychotic disorders (hazard ratio [HR], 1.42; 95% CI, 1.29-1.57), disruptive or impulse control disorders (HR, 1.36; 95% CI, 1.30-1.42), and neurodevelopmental disorders (HR, 1.22; 95% CI, 1.14-1.30) were more likely to revisit. Patients with substance use disorders (HR, 0.60; 95% CI, 0.55-0.66) were less likely to revisit. Markers of disease severity and health care access were associated with mental health revisits. Directing hospital and community interventions toward identified high-risk patients is needed to help mitigate recurrent mental health ED use and improve mental health care delivery.


Ergonomics, musculoskeletal disorders and computer work.
This review summarizes the knowledge regarding ergonomics and musculoskeletal disorders and the association with computer work. A model of musculoskeletal disorders and computer work is proposed and the evidence and implications of the model together with issues for future research is discussed. The model emphasizes the associations between work organization, psychosocial factors and mental stress on the one hand and physical demands and physical load on the other. It is hypothesized that perceived muscular tension is an early sign of musculoskeletal disorder, which arises as a result of work organizational and psychosocial factors as well as from physical load and individual factors. It is further hypothesized that perceptions of exertion and comfort are other possible early signs of musculoskeletal disorders in computer work. Interventions aimed at reducing musculoskeletal disorders due to computer work should be directed at both physical/ergonomic factors and work organizational and psychosocial factors. Interventions should be carried out with management support and active involvement of the individual workers.


Reducing sample sizes in genome scans: group sequential study designs with futility stops.
Group sequential study designs can greatly facilitate analyses of genetic linkage in complex traits. We recently proposed designs allowing stopping investigations early if the result is significant (König et al. [2001] Am. J. Hum. Genet. 69:590-600), thereby decreasing average sample sizes under the alternative hypothesis. However, average sample sizes were slightly increased under the null hypothesis. We now present designs where the analysis of markers is additionally stopped in case of futility, i.e., if the probability for significant results is sufficiently low. These sequential designs are applied to linkage analyses of single loci. We calculated sample sizes, time points, and critical boundaries for all analyses for 2- and 3-stage designs at an overall significance level of 0.0001. To confirm the validity of asymptotic approximations, Monte Carlo simulations were performed. The utility is demonstrated analyzing genome scan data provided for the Genetic Analysis Workshop 12. Application of the novel sequential designs yields tremendous decreases in average sample sizes, regardless of the size of the underlying genetic effect at investigated loci. Depending on the applied design, almost half of the sample size is spared on average. These enormous savings are expected to have a special impact on costs and time of large-scale studies such as genome scans.


Delayed-onset cytomegalovirus disease coded during hospital readmission in a multicenter, retrospective cohort of liver transplant recipients.
Delayed-onset cytomegalovirus (CMV) disease can occur among liver transplant recipients after CMV prophylaxis is stopped. We hypothesized that delayed-onset CMV disease (>100 days after transplant) occurs more commonly than early-onset CMV disease and is associated with clinical sepsis and death. Using 2004-2010 International Classification of Diseases, Ninth Revision, Clinical Modification billing data from 4 Healthcare Cost and Utilization Project state inpatient databases, we assembled a large and more representative cohort of 7229 adult liver transplant recipients from 26 transplant centers, and we identified demographics, comorbidities, CMV disease, and clinical sepsis coded during readmission and inpatient death. Multivariate analysis was performed with Cox proportional hazards models. Delayed-onset CMV disease occurred in 4.3% (n = 309), whereas early-onset CMV disease occurred in 2% (n = 142). Delayed-onset CMV disease was associated with previous transplant failure or rejection [adjusted hazard ratio (aHR), 1.4; 95% confidence interval (CI), 1.1-1.7]. Clinical sepsis > 100 days after transplant was associated with previous CMV disease (aHR, 1.3; 95% CI; 1.0-1.7), previous transplant failure or rejection (aHR, 2.1; 95% CI; 1.8-2.4), female sex (aHR, 1.3; 95% CI; 1.1-1.5), and several comorbidities. Death > 100 days after transplant was associated with delayed-onset CMV disease (aHR, 2.0; 95% CI; 1.6-2.6), transplant failure or rejection (aHR, 4.3; 95% CI; 3.4-5.5), increasing age by decade (aHR, 1.1; 95% CI; 1.0-1.2), and some comorbidities. In conclusion, delayed-onset CMV disease is more common than early-onset CMV disease among liver transplant recipients. Previous CMV disease may be a risk factor for clinical sepsis > 100 days after transplant, and delayed-onset CMV disease may be a risk factor for death > 100 days after transplant.


Cardiovascular complications of systemic lupus erythematosus: impact of risk factors and therapeutic efficacy-a tertiary centre experience in an Appalachian state.
Cardiovascular complications became a notable cause of morbidity and mortality in patients with lupus as therapeutic advancements became more efficient at managing other complications. The Appalachian community in Kentucky has a higher prevalence of traditional cardiovascular risk factors, predisposing them to cardiovascular events. Namely, the mean body mass index of the members of the Kentucky Appalachian community was reported at 33 kg/m2 and 94.3% of male members of this community use tobacco. We sought to identify risk factors that predispose patients with lupus to cardiovascular morbidities and examine the effect of immunomodulatory drugs. We identified 20 UKHS patients having both a lupus diagnosis and experienced at least one cardiovascular event. We chose three controls matched for birth-year ±5 years to each case. In a case-control design, we analysed lupus manifestations, cardiovascular risk factors and immunosuppressive therapies. We collected Systemic Lupus Erythematosus Disease Activity Index 2000 disease activity index during the cardiovascular event. We identified 308 patients with lupus from among all University of Kentucky Health System patients. 20 (6.5%) of such patients with lupus were confirmed to cardiovascular complication. Of those 20, 7 (35%) had experienced myocardial infarction, 10 (50%) had experienced stroke and 4 (20%) had peripheral ischaemia. Tobacco use and male gender were the only traditional cardiovascular risk factors higher in the cases group. Hydroxychloroquine and steroids were less utilised in the cases than in the controls (70% vs 100% in hydroxychloroquine, 30% vs 82% in steroids). Venous thrombosis was found to be significantly higher in the cases. On multivariate analysis, venous thrombosis remained significant. Despite tobacco use partially explaining the increased risk of cardiovascular disease among the cases group, the higher prevalence of venous thrombosis in the cases group suggests lupus as a potential additional risk factor of cardiovascular morbidity among patients with lupus in this Appalachian community.


Vertebral Distraction during Anterior Cervical Discectomy and Fusion Causes Postoperative Neck Pain.
Vertebral distraction is routinely performed during anterior cervical discectomy and fusion (ACDF). Overdistraction can injure the facet joints and may cause postoperative neck pain consequently. The purpose of this study was to investigate the clinical relevance of distraction force during ACDF. This study included 24 consecutive patients with single level cervical disc disease undergoing single level ACDF. We measure the maximum torque just before the the arm of the Caspar retractor was suspended by the rachet mechanism by turning the lever on the movable arm using a torque meter. In order to turn the lever using the torque driver, we made a linear groove on the top of the lever. We compared the neck disability index (NDI) and visual analogue scale (VAS) scores between the high torque group (distraction force>6 kgf·cm) and the low torque group (distraction force≤6 kgf·cm) at routine postoperative intervals of 1, 3, 5 days and 1, 3, 6 months. The VAS scores for posterior neck pain had a linear correlation with torque at postoperative 1st and 3rd days (y=0.99×-1.1, r(2)=0.82; y=0.77×-0.63, r(2)=0.73, respectively). VAS scores for posterior neck pain were lower in the low torque group than in the high torque group on both 1 and 3 days postoperatively (3.1±1.3, 2.6±1.0 compared with 6.0±0.6, 4.9±0.8, p<0.01). However, the difference in NDI scores was not statistically significant in all postoperative periods. Vertebral distraction may cause posterior neck pain in the immediate postoperative days. We recommend not to distract the intervertebral disc space excessively with a force of more than 6.0 kgf·cm.


Disposal of pesticide waste from agricultural production in the Al-Batinah region of Northern Oman.
During the last two decades Oman has experienced rapid economic development but this has been accompanied by environmental problems. Manufacturing and agricultural output have increased substantially but initially this was not balanced with sufficient environmental management. Although agriculture in Oman is not usually considered a major component of the economy, government policy has been directed towards diversification of national income and as a result there has been an increasing emphasis on revenue from agriculture and an enhancement of production via the use of irrigation, machinery and inputs such as pesticides. In recent years this has been tempered with a range of interventions to encourage more sustainable production. Certain pesticides have been prohibited; there has been a promotion of organic agriculture and an emphasis on education and awareness programs for farmers. The last point is of especial relevance given the nature of the farm labour market in Oman and a reliance on expatriate and often untrained labour. The research, through a detailed stratified survey, explores the state of knowledge at farm-level regarding the safe disposal of pesticide waste and what factors could enhance or indeed operate against the spread and implementation of that knowledge. Members of the recently constituted Farmers Association expressed greater environmental awareness than their non-member counterparts in that they identified a more diverse range of potential risks associated with pesticide use and disposed of pesticide waste more in accordance with government policy, albeit government policy with gaps. Workers on farms belonging to Association members were also more likely to adhere to government policy in terms of waste disposal. The Farmers Association appears to be an effective conduit for the diffusion of knowledge about pesticide legislation and general awareness, apparently usurping the state agricultural extension service.


Anabolic-androgenic steroid use among california community college student-athletes.
To determine the incidence of anabolic- androgenic steroid use among a sample of community college student-athletes; also, to compare various aspects of users and nonusers, as well as to describe usage patterns. A survey following random stratified cluster sampling techniques was administered to 10 California community colleges. A group of 1,185 male and female student- athletes. An anonymous 27-item, valid, and reliable questionnaire was administered surveying anabolic-androgenic steroid use and usage patterns. Of all student-athletes sampled, 3.3% were anabolic -androgenic steroid users. Gender-specific incidence rates were 4.2% for males and 1.2% for females. Anabolic- androgenic steroid users tended to be older males, usually in their second year of college. The users were more often minorities. Users believed that they were knowledgeable about anabolic-androgenic steroids, and that the rates of usage were higher than reported. Their sources of steroid information were often lifting partners and fellow athletes. Use of these drugs was most often in cycles (mean of 6.7 weeks) and was frequently done using multiple anabolic-androgenic steroids at a time. The average number of cycles completed was 2.9. A wide variety of steroids were used by the student-athletes, of which most were obtained from illegal sources. Anabolic-androgenic steroid use among Califonia community college student-athletes were similar to other previous research studies involving high school and university student-athletes.


Antioxidants in raspberry: on-line analysis links antioxidant activity to a diversity of individual metabolites.
The presence of antioxidant compounds can be considered as a quality parameter for edible fruit. In this paper, we studied the antioxidant compounds in raspberry (Rubus idaeus) fruits by high-performance liquid chromatography (HPLC) coupled to an on-line postcolumn antioxidant detection system. Both developmental and genetic factors were assessed by comparing fruits from a single cultivar of different ripening stages and by comparing ripe fruits of 14 raspberry cultivars, respectively. The HPLC-separated antioxidant compounds were identified using HPLC-photodiode array coupled to mass spectrometry (quadrupole time-of-flight tandem mass spectrometry), using a reference lock mass for determining accurate masses. The dominant antioxidants could be classified as anthocyanins, ellagitannins, and proanthocyanidin-like tannins. During fruit ripening, some anthocyanins were newly produced, while others, like cyanidin-3-glucoside, were already present early in fruit development. The level of tannins, both ellagitannins and proanthocyanidin-like tannins, was reduced strongly during fruit ripening. Among the 14 cultivars, major differences (>20-fold) were observed in the levels of pelagonidin type anthocyanins and some proanthocyanidin type tannins. The content of ellagitannins varied approximately 3-fold. The findings presented here suggest that the content of individual health-promoting compounds varies significantly in raspberry, due to both developmental and genetic factors. This information will assist in the future development and identification of raspberry lines with enhanced health-promoting properties.


Coronary artery stenoses: detection with calcium scoring, CT angiography, and both methods combined.
To investigate prospectively the relative accuracy of computed tomographic (CT) angiography, calcium scoring (CS), and both methods combined in demonstrating coronary artery stenoses by using conventional angiography as the reference standard. The study was approved by the institutional review board Human Research Ethics Committee, and all patients completed written informed consent. Fifty patients (40 men, 10 women) aged 62 years +/- 11 (+/- standard deviation) who were suspected of having coronary artery disease underwent both conventional coronary angiography and multisection coronary CT angiography with CS. Sensitivity and specificity of CS, CT angiography, and both methods combined in demonstrating luminal stenosis greater than or equal to 50% were determined for each arterial segment, coronary vessel, and patient. Receiver operating characteristic (ROC) curves were generated for CS prediction of significant stenosis, and the Mann-Whitney U test was used for comparison of CS between groups. When used with segment-specific electrocardiographic phase reconstructions, CT angiography demonstrated stenosed segments with 79% sensitivity and 95% specificity. Mean calcium score was greater in segments, vessels, and patients with stenoses than in segments, vessels, and patients without stenoses (P < .001 for all); nine (16%) of 56 stenosed segments, however, had a calcium score of 0. The patient calcium score correlated strongly with the number of stenosed arteries (Spearman rho = 0.75, P < .001). CS was more accurate in demonstrating stenosis in patients than in segments (areas under ROC curve were 0.88 and 0.74, respectively). CT angiography, however, was more accurate than CS in demonstrating stenosis in patients, vessels, and segments. The sensitivity and specificity of CS varied according to the threshold used, but when the calcium score cutoff (ie, >150) matched the specificity of CT angiography (95%), the sensitivity of CS in demonstrating stenosed segments was 29% (compared with 79% for CT angiography). Combining CT angiography with CS (at threshold of 400) improved the sensitivity of CT angiography (from 93% to 100%) in demonstrating significant coronary disease in patients, without a loss of specificity (85%); this finding, however, was not statistically significant. CT angiography is more accurate than CS in demonstrating coronary stenoses. A patient calcium score of greater than or equal to 400, however, can be used to potentially identify patients with significant coronary stenoses not detected at CT angiography.


A novel graph-based similarity measure for 2D chemical structures.
In this paper, we propose a graph-based method to measure the similarity between chemical compounds described by 2D form. Our main idea is to measure the similarity between two compounds based on edges, nodes, and connectivity of their common subgraphs. We applied the proposed similarity measure in combination with a clustering method to more than eleven thousand compounds in the chemical compound database KEGG/LIGAND and discovered that compound clusters with highly similar structure compounds that share common names, take part in the same pathways, and have the same requirement of enzymes in reactions. Furthermore, we discovered the surprising sameness between pathway modules identified by clusters of similar structure compounds and that identified by genomic contexts, namely, operon structures of enzyme genes.


Diagnostic accuracy of circulating microRNA in hepatitis B virus-related hepatocellular carcinoma: a meta-analysis based on Asian data.
hepatitis B virus (HBV) is the main risk factor for hepatocellular carcinoma (HCC). We performed a meta-analysis based on Asian data to evaluate the diagnostic accuracy of circulating microRNA as a non-invasive biomarker in the diagnosis of HBV-related HCC. a comprehensive literature search (updated to May 12, 2021) in PubMed, Embase, Web of Science, Wanfang Database, and China National Knowledge Infrastructure (CNKI) was performed to identify eligible studies. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) for diagnosing HBV-related HCC were pooled in this meta-analysis. A subgroup analysis was performed to explore heterogeneity, and Deeks' funnel plot was used to assess publication bias. a total of 19 articles including 32 studies were included in the current meta-analysis. The overall sensitivity, specificity, PLR, NLR, DOR and AUC were 0.83 (95 % CI: 0.79 to 0.87), 0.78 (95 % CI: 0.73 to 0.83), 3.9 (95 % CI: 3.0 to 4.9), 0.21 (95 % CI: 0.16 to 0.27), 18 (95 % CI: 12 to 27) and 0.88 (95 % CI: 0.85 to 0.91), respectively. Subgroup analysis shows that miRNA clusters with a large sample size showed better diagnostic accuracy. Although there is no publication bias, the research still has some limitations. circulating miRNAs could serve as a potential non-invasive biomarker in diagnosing HBV-related HCC in Asian populations.


Enhanced elimination of perfluorooctane sulfonic acid by menstruating women: evidence from population-based pharmacokinetic modeling.
Human biomonitoring studies have shown that concentrations of perfluorooctane sulfonic acid (PFOS) in men are higher than in women. We investigate sex differences in elimination of PFOS by fitting a population-based pharmacokinetic model to six cross-sectional data sets from 1999 to 2012 from the US National Health and Nutrition Examination Survey (NHANES) and derive human first-order elimination rate constants (kE) and corresponding elimination half-lives (t1/2) for PFOS, where t1/2 = ln 2/kE. We use a modified version of the Ritter population-based pharmacokinetic model and derive elimination rate constants separately for men and women. The model accounts for population-average lifetime changes in PFOS intake, body weight, and menstruation rate. We compare the model-derived elimination rate constant for hypothetical nonmenstruating women to the elimination rate constant for men and women when menstruation is included as a loss process to evaluate the hypothesis that loss of PFOS by menstruation is an important process for women. The modeled elimination half-life for men is 4.7 years, and the modeled elimination half-life for women when excluding losses from menstruation is 3.7 years. The elimination half-life for women when menstruation is included in the model is 4.0 years. Thus, menstruation accounts for 30% of the discrepancy in elimination of PFOS between men and women. The remaining discrepancy is likely due to other sex-specific elimination routes that are not considered in our modeling.


Internal fields of soot fractal aggregates.
This work uses the discrete dipole approximation (DDA) to examine the internal electric field within a simulated carbon soot fractal aggregate in fixed and random orientations. For fixed orientations, deviations of the internal field magnitude up to ±50% from that assumed by the Rayleigh-Debye-Gans Approximation (RDGA) are found. Given the refractive index of the aggregate monomers and conditions for the validity of the approximation, such large deviations are no surprise. Yet despite this deviation, the far-field scattered intensity from such aggregates agrees surprisingly well with that described by the RDGA. Moreover, if the average over an ensemble of many random aggregate-orientations is calculated, both the DDA and RDGA scattered intensities obey the well-known power-law functionality in terms of the scattering wave vector and show a forward-angle intensity-maximum proportional to the square of the number of monomers. The explanation for this lies in the over and under estimations made by the approximation of the internal field, which apparently mostly cancel upon integration to yield the scattered intensity. It is shown that this error cancellation is related to the fractal structure of the aggregate and that the agreement between the DDA and RDGA improves with aggregates of increasing size provided the fractal dimension is less than two. Overall, the analysis suggests that both the special fractal character of the aggregate and its orientational averaging is important to account for the experimentally observed validity of the RDGA despite its poor description of the internal fields.


Insights into AMS/PCAT transporters from biochemical and structural characterization of a double Glycine motif protease.
The secretion of peptides and proteins is essential for survival and ecological adaptation of bacteria. Dual-functional ATP-binding cassette transporters export antimicrobial or quorum signaling peptides in Gram-positive bacteria. Their substrates contain a leader sequence that is excised by an N-terminal peptidase C39 domain at a double Gly motif. We characterized the protease domain (LahT150) of a transporter from a lanthipeptide biosynthetic operon in Lachnospiraceae and demonstrate that this protease can remove the leader peptide from a diverse set of peptides. The 2.0 Å resolution crystal structure of the protease domain in complex with a covalently bound leader peptide demonstrates the basis for substrate recognition across the entire class of such transporters. The structural data also provide a model for understanding the role of leader peptide recognition in the translocation cycle, and the function of degenerate, non-functional C39-like domains (CLD) in substrate recruitment in toxin exporters in Gram-negative bacteria.


On the mechanism of uptake of globular proteins by polyelectrolyte brushes: a two-gradient self-consistent field analysis.
We present model calculations for the interaction of a protein-like inhomogeneously charged nanoscale object with a layer of densely grafted polyelectrolytes ("polyelectrolyte brush"). The motivation of this work is the recent experimental observation that proteins that carry an overall negative charge are absorbed into negatively charged polyelectrolyte brushes. Two-gradient self-consistent field (2G-SCF) calculations have been performed to unravel the physical mechanism of the uptake of protein thus effected. Our results prove that an overall neutral, protein-like object can electrostatically be attracted and therefore spontaneously driven into a polyelectrolyte brush when the object has two faces (patches, domains), one with a permanent positive charge and the other with a permanent negative charge. Using a 2G-SCF analysis, we evaluate the free energy of insertion, such that the electric dipole of the inclusion is oriented parallel to the brush surface. An electroneutral protein-like object is attracted into the brush because the polyelectrolyte brush interacts asymmetrically with the charged patches of opposite sign. At high ionic strength and low charge density on the patches, the attraction cannot compete with the repulsive excluded-volume interaction. However, for low ionic strengths and sufficiently high charge density on the patches, a gain on the order of k(B)T per charge becomes possible. Hence, the asymmetry of interaction for patches of different charges may result in a total attractive force between the protein and the brush. All results obtained herein are in excellent agreement with recent experimental data.


A novel Laennec's capsule tunnel approach for pure laparoscopic left hemihepatectomy: a propensity score matching study.
With the development of laparoscopic hepatectomy, there are different surgical approaches and pedicle anatomical methods for laparoscopic left hepatectomy. Combined with our practical experience, we proposed a method of transhepatic Laennec membrane tunnel for laparoscopic left hemihepatectomy (LT-LLH) and investigated the feasibility by comparison with the extrahepatic Glissonian approach for laparoscopic left hemihepatectomy (GA-LLH). The data of patients who underwent laparoscopic left hepatectomy in the Department of Hepatobiliary Pancreatic surgery of Fujian Provincial Hospital from December 2019 to March 2022 were analyzed retrospectively. Among them, 45 cases underwent laparoscopic left hemihepatectomy with an extrahepatic Glissonian approach, and 38 cases underwent laparoscopic left hemihepatectomy via transhepatic Laennec membrane tunnel approach. A 1:1 propensity score matching (PSM) method was performed to compare the perioperative indexes and long-term tumor prognosis between the two groups. After 1:1 PSM, 33 patients in each group were selected for further analysis. Compared with the GA-LLH group, the operation time of the LT-LLH group was shorter. There was no significant difference in the incidence of total complications between the two groups. Moreover, no statistical differences were found in disease-free survival and overall survival between the two groups. It is safe, faster, and convenient for selective appropriate cases to carry out laparoscopic left hemihepatectomy through the hepatic Laennec membrane tunnel, which is suitable for clinical promotion.


Apolipoprotein changes associated with the plasma lipid-regulating activity of gemfibrozil in cholesterol-fed rats.
Gemfibrozil (Lopid) is a new plasma lipid-regulating drug that decreases very low and low density lipoprotein (VLD/LDL) and increases high density lipoprotein (HDL) concentrations in man. The present experiments tested the effects of gemfibrozil on plasma lipoproteins and apolipoproteins in rats fed high fat/high cholesterol diets. Compared to chow-fed rats, cholesterol feeding for 2 weeks (20% olive oil/2% cholesterol) produced the expected increases in VLDL and intermediate density lipoprotein (IDL) while lowering plasma HDL. This was documented by using three methods of lipoprotein isolation: sequential ultracentrifugation, density gradient ultracentrifugation, and agarose gel filtration. Gemfibrozil gavaged at 50 mg/kg per day for 2 weeks during cholesterol feeding prevented these changes such that lipoprotein patterns were similar to those in chow-fed animals. Whole plasma apoE and apoA-I concentrations were decreased and apoB increased due to cholesterol feeding as determined by electroimmunoassay, but again gemfibrozil treatment prevented these diet-induced alterations. Gradient polyacrylamide gel electrophoresis patterns of the total d less than 1.21 g/ml lipoprotein fractions reflected the changes in apolipoprotein concentrations and further demonstrated a greater increase of apoBl compared to apoBh in cholesterol-fed rats. Gemfibrozil lowered the concentration of both apoB variants and prevented the shift of apoE from HDL to lower density lipoproteins. Changes in the distribution of apoE were confirmed using agarose gel column chromatography followed by electroimmunoassay. These methods also revealed a shift of apoA-IV from HDL to the d greater than 1.21 g/ml, lipoprotein-free fraction with gemfibrozil treatment when blood was taken from fasted or postabsorptive animals. Since it was also noted that in chow-fed rats more apoA-IV was present in the d greater than 1.21 g/ml fraction in the postabsorptive or fed state compared to fasted animals, it could be postulated that the shift of apoA-IV into this fraction in gemfibrozil-treated rats is related to an accelerated clearance of chylomicrons. It is concluded that gemfibrozil largely prevents the accumulation of abnormal lipoproteins in this model of dyslipoproteinemia, and that apoE may play a critical role in this normalization process.


Leucine and lysine intakes are highly associated with serum adiponectin levels in asymptomatic adults.
Adiponectin has anti-inflammatory, antiatherosclerotic properties and it is involved in metabolic regulation, especially by sensitizing tissues for insulin. Adherence to the Mediterranean diet has been shown to have a positive effect on adiponectin levels. Therefore, our aim was to assess asymptomatic general population of the Mediterranean part of Slovenia and to evaluate the correlations between serum adiponectin levels (SALs) and diet components, dietary habits, lifestyle parameters, metabolic syndrome (MetS) components and inflammatory markers. Healthy adults aged 25-49 participated in the cross-sectional study. Linear correlation analyses were used to examine SALs on diet components, dietary habits, lifestyle parameters and all risk factors. A positive correlation between the ratio of leucine:lysine intake and adiponectin and a negative correlation between adiponectin and presence of already two components of MetS were found. Moreover, we confirmed the negative correlations between adiponectin and C-reactive protein (CRP), but found a negative correlation between adiponectin and visfatin. Furthermore, hierarchical multiple regression analyses confirmed that besides lower homeostasis model assessment insulin resistance (HOMA-IR), CRP, homocysteine and BMI, also higher ratio of leucine:lysine contributes to the prediction of higher level of adiponectin. Our results indicate that high leucine:lysine intake ratio may promote the increase in SALs in clinically asymptomatic adults. On the other hand, lower SALs are due to obesity, inflammation and presence of already 2 components of metabolic syndrome.


Descriptions of some unusual digeneans from Boops boops L. (Sparidae) and a complete checklist of its metazoan parasites.
Six species of digeneans, including three new host records, are described from the bogue Boops boops off the Spanish NE Atlantic and the Mediterranean coasts. The species involved are: Robphildollfusium martinezgomezi López-Román, Gijón-Botella, Kim & Vilca-Choque, 1992, Magnibursatus caudofilamentosa (Reimer, 1971) Gibson & Køie, 1991, Lepocreadium album Stossich, 1890, Steringotrema pagelli (van Beneden, 1871) Odhner, 1911, Tetrochetus coryphaenae Yamaguti, 1934 and Stephanostomum euzeti Bartoli & Bray, 2004 (metacercaria). B. boops is a new host for 11 metazoan parasites (six digeneans, three acanthocephalans, one copepod and one isopod) recovered in this study. These are reported and incorporated into a complete checklist of the metazoan parasites of B. boops throughout its distributional range. It comprises summarised information for 67 species in 260 host-parasite records and includes the name of the parasite species, the locality of the host, and the author and date of the published record. The taxonomy is updated and annotations are made on the validity of the records and synonymies.


Polypeptide synthesis in Junín virus-infected BHK-21 cells.
Analysis by immune precipitation and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of intracellular [35S]-methionine-labelled specific Junín virus polypeptides demonstrated synthesis of the nucleoprotein (Np64) between 24 to 96 hr post-infection (p.i.). Two glycoproteins with apparent molecular weights (Mr) of 72,000 (Gp72) and 38,000 (Gp38) were detected by pulse labelling with [35S]-methionine or sugar precursor at about 48 hr p.i. The rate of synthesis of Gp38 increased up to 96 hr p.i. with concomitant decrease of Gp72. During pulse-chase experiments, Gp72 was cleaved to Gp38. These results suggest that Gp72 may be a precursor of the envelope structural glycoprotein. Using sera to virion fractions we found that Gp72 and Gp38 did not share antigenic determinants with Np64. We also identified a 200,000 Mr polypeptide (P200) in infected cells. The possibility that P200, Gp72 and Np64 are virus coded products is discussed.


[The "optimal rate" for the heart beat of a homeotherm].
The optimal heart-rate was studied in natural conditions of hemodynamics and on stabilizing the left ventricle load and volume with a balloon. The coronary blood-flow was traced with the aid of electromagnetic fluorometer. Post-occlusion reactive hyperemia estimated reserves of the coronary blood-flow. On stabilizing the left ventricle load and volume, its contractility was higher with faster heart-rate. With the fastest heart-rate, a considerable reserve of the coronary blood-flow was still preserved. Apparently under conditions of natural hemodynamics, the optimal heart-rate (100-180/min) and the decline of contractility with fast heart-rate are due to decrease in filling of the heart caves with the blood per 1 sistole at a constant 1 min volume of the blood-flow.


Vitamin D Sufficiency Has a Limited Effect on Placental Structure and Pathology: Placental Phenotypes in the VDAART Trial.
Vitamin D insufficiency during pregnancy is widespread. The effects of active vitamin D on the human placenta in vivo are unknown. We test the hypotheses that 25(OH)D sufficiency (arbitrarily defined as 25(OH)D ≥32 ng/mL) modulates placental structure and function in vivo in a population of women whose offspring are at risk for childhood asthma, and that placental pathology is more common in offspring that evolve asthma at age 3. Pregnant volunteers in the St. Louis, MO, cohort of the Vitamin D Antenatal Asthma Reduction Trial (VDAART, NIH grant #HL091528) participated in a nested case-control study and consented for the study of placentas after delivery. Maternal concentrations of 25(OH)D were measured at trial entry and in the third trimester. The histopathology of the placentas from women with sufficient 25(OH)D, versus insufficient, showed no clinically significant differences, but morphometry revealed villi of women with sufficient third-trimester 25(OH)D had a higher villous surface density. Notably, analyses of transcripts, extracted from formalin-fixed paraffin-embedded specimens, revealed higher expression of INTS9, vWF, MACC1, and ARMS2, and diminished expression of the CNTN5 genes in the insufficient group. A larger proportion of placentas showed chronic chorioamnionitis in offspring with versus without asthma at age 3. These findings suggest that maternal 25(OH)D insufficiency has a limited effect on human placental villous histopathology and morphometry, but attenuates a small number of placental gene expression profiles in this selected population. The association of placental chronic chorioamnionitis and offspring asthma is worthy of further study.


Exercise therapy for arm function in stroke patients: a systematic review of randomized controlled trials.
Assessment of the available evidence for the effectiveness of exercise therapy to improve arm function in patients who have suffered from a stroke. A systematic search of bibliographical databases and reference checking were performed to identify publications on randomized controlled trials (RCTs) which evaluated the effect of exercise therapy on arm function in stroke patients. The methodological quality was assessed systematically by two raters, based on a standardized list of methodological criteria. Study characteristics, such as the chronicity and severity of impairment of the patient population, the amount and duration of interventions, and specific methodological criteria, were related to reported effects. Thirteen RCTs were identified, six of which reported positive results on an arm function test. In five of these six studies there was a contrast in amount or duration of exercise therapy between groups. Methodological scores ranged from 5 to 15 (maximum possible score: 19 points). Insufficient evidence made it impossible to draw definitive conclusions about the effectiveness of exercise therapy on arm function in stroke patients. The difference in results between studies with and without contrast in the amount or duration of exercise therapy between groups suggests that more exercise therapy may be beneficial.


Photoinduced Carbonyl Radical Luminescence in Host-Guest Systems.
Developing a free radical emission system in different states, especially in water, is highly challenging and desired. Herein, a host-guest coassembly strategy was used to protect the in situ photoactivated radical emission of carbonyl compounds in solid and aqueous solutions by doping them into a series of small molecules with hydroxyl groups. The intermolecular interactions between host and guest and the electron-donating ability of the hydroxyl group can significantly promote the formation and stabilization of luminescence by carbonyl radicals. Accordingly, the stimuli-responsive property of the free radical system was investigated in detail, and the self-assembled aggregates showed photoactive and thermoresponsive behaviors. In addition, an advanced ammonia compound identification system can be built based on a radical emission system. Our design strategy sheds light on developing free radical systems that can emit in various states, which will greatly broaden the application range of free radicals.


Strategies to improve ingestive behaviour with reference to critical illness.
The complex interplay between neural and endocrine responses following food intake regulates ingestive behaviour and ultimately determines subsequent energy intake. These processes include cognitive, gastrointestinal-derived and metabolic mechanisms. Such physiological responses to the ingestion of food initiate short- to medium-term inhibition of intake (satiety). However, in clinical states in which systemic inflammation is evident there is a more profound satiety response and a clear absence of motivation to eat that is evident as loss of appetite. These negative influences on energy intake can contribute to poor nutritional status, and consequently poor physical function, and impact on rehabilitation and recovery. Cytokine mediators of the inflammatory response directly influence feeding behaviour at the hypothalamic nuclei and may explain the lack of motivation and desire for food. However, additional detrimental effects on appetite are brought about because of alterations in intermediary metabolism present in inflammation-induced catabolism. This process forms part of the host response to inflammation and may explain symptoms, such as early satiety, frequently reported in many patient groups. In clinical states, and cancer in particular, pharmacological strategies have been employed to ameliorate the inflammatory response in an attempt to improve energy intake. Some success of this approach has been reported following administration of substrates such as EPA. Novel strategies to improve intake through administration of anti-cytokine drugs such as thalidomide may also be of benefit. However, drugs that oppose the actions of neurotransmitter pathways involved in central induction of satiety, such as 5-hydroxytryptamine, have failed to improve intake but appear to enhance enjoyment of food. Such findings indicate that therapeutic nutritional targets can only be achieved where novel pharmacological therapies can be supported by more innovative and integrated dietary management strategies. Many of these strategies remain to be elucidated.


[Isolation of the specific endonuclease BamH1 in the multicyclic cultivation of Bacillus amyloliquefaciens].
The present article deals with the study of the multicyclic process of the cultivation of B. amyloliquefaciens in a liquid medium prepared from natural raw materials and with obtaining restrictase Bam H1 from the biomass with different microbiological characteristics. The selected medium has been found to be suitable for the realization of the multicyclic cultivation process on an industrial scale. The tendency towards a drop in the level of nonspecific nucleases simultaneously with a decrease in the specific growth rate has been revealed. A simplified scheme for the purification of the restricting endonuclease is proposed.


Acute ischemic stroke with tandem lesions: technical endovascular management and clinical outcomes from the ESCAPE trial.
Tandem occlusions of the extracranial carotid and intracranial carotid or middle cerebral artery have a particularly poor prognosis without treatment. Several management strategies have been used with no clear consensus recommendations. We examined subjects with tandem occlusions enrolled in the ESCAPE trial and their outcomes. Data are from the ESCAPE trial. Additional data were sought on interventions for each subject. There were 54 (17%) subjects with tandem extracranial and intracranial occlusions. Patients in the endovascular treatment arm (n=30) were more likely to be younger (median age 66 years, p<0.01), male (66.7%, p=0.03), diabetic, and without atrial fibrillation. Subjects with tandem occlusions were more likely to have intracranial internal carotid artery occlusions than M1 occlusions (p<0.01). Of the 30 intervention-arm subjects, 17 (57%) underwent emergency endovascular treatment of the extracranial disease, 10 subjects before and seven subjects after intracranial thrombectomy. Of the remaining 13 subjects, only four required staged carotid revascularization due to persistent severe carotid stenosis; four had cervical pseudo-occlusions with no residual stenosis after large distal carotid thrombus burden aspiration/retrieval. Outcomes were similar between subjects with and without tandem lesions. The use of antithrombotic agents after acute carotid artery stenting was variable but no symptomatic intracerebral hemorrhage was seen in subjects who underwent emergency endovascular treatment of extracranial carotid artery. Tandem occlusions occurred in one-sixth of patients and were treated highly variably within the ESCAPE trial. While outcomes were similar, the best method to treat the carotid artery in patients with tandem occlusion awaits further randomized data. NCT01778335.


Airway management in croup and epiglottitis.
Treatment techniques for airway obstruction in croup and epiglottitis are reviewed in the medical literature. Series totaling 295 nasotracheal intubations, and 591 tracheostomies were reviewed. There were two deaths attributable to airway complications in 126 patients in whom nasotracheal intubation was carried out. In three patients subglottic granulation tissue and subglottic stenoses developed from short-term nasotracheal intubation. There were no subglottic stenoses or tracheal stenoses reported in the 591 tracheostomies. From this review, it would seem feasible to use nasotracheal intubation for short-term airway treatment in croup and epiglottitis. The increasing occurrence of laryngeal and tracheal complications with long-term intubation suggests that tracheostomy be considered in such cases.


Endotoxin exposure and inflammation markers among agricultural workers in Colorado and Nebraska.
The adverse respiratory effects of agricultural dust inhalation are mediated in part by endotoxin, a constituent of gram-negative bacterial cell walls. This study quantified personal work-shift exposures to inhalable dust, endotoxin, and its reactive 3-hydroxy fatty acid (3-OHFA) constituents among workers in grain elevators, cattle feedlots, dairies, and on corn farms. Exposures were compared with post-work-shift nasal lavage fluid inflammation markers and respiratory symptoms. Breathing-zone personal air monitoring was performed over one work shift to quantify inhalable dust (Institute of Medicine samplers), endotoxin (recombinant factor C [rFC] assay), and 3-OHFA (gas chromatography/mass spectrometry). Post-shift nasal lavage fluids were assayed for polymorphonuclear neutrophils (PMN), myeloperoxidase (MPO), interleukin 8 (IL-8), albumin, and eosinophilic cation protein (ECP) concentrations. The geometric mean (GSD) of endotoxin exposure (rFC assay) among the 125 male participants was 888 +/- (6.5) EU/m(3), and 93% exceeded the proposed exposure limit (50 EU/m(3)). Mean PMN, MPO, albumin, and ECP levels were two- to threefold higher among workers in the upper quartile of 3-OHFA exposure compared to the lowest exposure quartile. Even numbered 3-OHFA were most strongly associated with nasal inflammation. Symptom prevalence was not elevated among exposed workers, possibly due to endotoxin tolerance or a healthy worker effect in this population. This is the first study to evaluate the relationship between endotoxin's 3-OHFA constituents in agricultural dust and nasal airway inflammation. More research is needed to characterize the extent to which these agents contribute to respiratory disease among agricultural workers.


Correlation of carotid artery reactivity with cardiovascular risk factors and coronary artery vasodilator responses in asymptomatic, healthy volunteers.
Carotid artery reactivity (CAR%), involving carotid artery diameter responses to a cold pressor test (CPT), is a noninvasive measure of conduit artery function in humans. This study examined the impact of age and cardiovascular risk factors on the CAR% and the relationship between CAR% and coronary artery vasodilator responses to the CPT. Ultrasound was used to measure resting and peak carotid artery diameters during the CPT, with CAR% being calculated as the relative change from baseline (%). We compared CAR% between young (n = 50, 24 ± 3 years) and older participants (n = 44, 61 ± 8 years), and subsequently assessed relationships between CAR% and traditional cardiovascular risk factors in 50 participants (44 ± 21 years). Subsequently, we compared left anterior descending (LAD) artery velocity (using transthoracic Doppler) with carotid artery diameter (i.e. CAR%) during the CPT (n = 33, 37 ± 17 years). A significantly larger CAR% was found in young versus older healthy participants (4.1 ± 3.7 versus 1.8 ± 2.6, P < 0.001). Participants without cardiovascular risk factors demonstrated a higher CAR% than those with at least two risk factors (2.9 ± 2.9 versus 0.5 ± 2.9, P = 0.019). Carotid artery diameter and LAD velocity increased during CPT (P < 0.001). Carotid diameter and change in velocity correlated with LAD velocity (r = 0.486 and 0.402, P < 0.004 and 0.02, respectively). Older age and cardiovascular risk factors are related to lower CAR%, while CAR% shows good correlation with coronary artery responses to the CPT. Therefore, CAR% may represent a valuable technique to assess cardiovascular risk, while CAR% seems to reflect coronary artery vasodilator function.


Analysis of factors associated with extended recovery time after colonoscopy.
A common limiting factor in the throughput of gastrointestinal endoscopy units is the availability of space for patients to recover post-procedure. This study sought to identify predictors of abnormally long recovery time after colonoscopy performed with procedural sedation. In clinical research, this type of study would be performed using only one regression modeling approach. A goal of this study was to apply various "machine learning" techniques to see if better prediction could be achieved. Procedural data for 31,442 colonoscopies performed on 29,905 adult patients at Massachusetts General Hospital from 2011 to 2015 were analyzed to identify potential predictors of long recovery times. These data included the identities of hospital personnel, and the initial statistical analysis focused on the impact of these personnel on recovery time via multivariate logistic regression. Secondary analyses included more information on patient vitals both to identify secondary predictors and to predict long recoveries using more complex techniques. In univariate analysis, the endoscopist, procedure room nurse, recovery room nurse, and surgical technician all showed a statistically significant relationship to long recovery times, with p-value below 0.0001 in all cases. In the multivariate logistic regression, the most significant predictor of a long recovery time was the identity of the recovery room nurse, with the endoscopist also showing a statistically significant relationship with a weaker effect. Complex techniques led to a negligible improvement over simple techniques in prediction of long recovery periods. The hospital personnel involved in performing a colonoscopy show a strong association with the likelihood of a patient spending an abnormally long time recovering from the procedure, with the most pronounced effect for the nurse in the recovery room. The application of more advanced approaches to improve prediction in this clinical data set only yielded modest improvements.


Effect of enterobacterial common antigen on mouse virulence of Salmonella typhimurium.
A series of nearly isogenic O4-12, and O-6,7 Salmonella typhimurium strains differing in regard to the enterobacterial common antigen (ECA) were constructed by conjugation. When tested in intraperitoneal infection of mice, the O-4,12 strains containing ECA were more virulent than their O-4,12 sister recombinants without ECA (P = less than 0.001). The same difference could be shown with ECA-positive and ECA-negative S. typhimurium derivatives, whose O antigens were of the group C type (O-6,7). The ECA-positive and ECA-negative O-4,12 strains did not differ in their growth rates in broth or clearance rates in vivo.