Sweet and sour--oxidative and carbonyl stress in neurological disorders.
The nervous system is a unique network of different cell types and comprises a variety of proteins, lipids, and carbohydrates that have an important interplay with all major organs in the body. Homeostatic regulation of nervous tissue turnover must be carefully controlled, taking into account interactions of the nervous, endocrine, and immune systems. Clinical conditions affecting the nervous system range from mild cognitive perturbations such as headache, to life-threatening acute courses such as meningitis and glioblastoma, and to chronic neurodegenerative diseases such as multiple sclerosis. One unifying feature in normal developmental or homeostatic functions and clinical dysfunctions within the nervous system is redox regulation, with an imbalance in oxidative/carbonyl stress versus antioxidants being characteristic of pathological conditions. In this review we consider the state of current knowledge regarding structural, genetic, proteomic, histopathological, clinical, and therapeutic perspectives of oxidative and carbonyl stress within the nervous system.


Reliable estimation of capillary transit time distributions using DSC-MRI.
The regional availability of oxygen in brain tissue is traditionally inferred from the magnitude of cerebral blood flow (CBF) and the concentration of oxygen in arterial blood. Measurements of CBF are therefore widely used in the localization of neuronal response to stimulation and in the evaluation of patients suspected of acute ischemic stroke or flow-limiting carotid stenosis. It was recently demonstrated that capillary transit time heterogeneity (CTH) limits maximum oxygen extraction fraction (OEF(max)) that can be achieved for a given CBF. Here we present a statistical approach for determining CTH, mean transit time (MTT), and CBF using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI). Using numerical simulations, we demonstrate that CTH, MTT, and OEF(max) can be estimated with low bias and variance across a wide range of microvascular flow patterns, even at modest signal-to-noise ratios. Mean transit time estimated by singular value decomposition (SVD) deconvolution, however, is confounded by CTH. The proposed technique readily identifies malperfused tissue in acute stroke patients and appears to highlight information not detected by the standard SVD technique. We speculate that this technique permits the non-invasive detection of tissue with impaired oxygen delivery in neurologic disorders such as acute ischemic stroke and Alzheimer's disease during routine diagnostic imaging.


Re-feeding after starvation involves a temporal shift in the control site of glycogen synthesis in rat muscle.
The starved-to-fed transition is accompanied by rapid glycogen deposition in skeletal muscles. On the basis of recent findings [Bräu, Ferreira, Nikolovski, Raja, Palmer and Fournier (1997) Biochem. J. 322, 303-308] that during recovery from exercise there is a shift from a glucose 6-phosphate/phosphorylation-based control of glycogen synthesis to a phosphorylation-based control alone, this paper seeks to establish whether a similar shift occurs in muscle during re-feeding after starvation in the rat. Chow re-feeding after 48 h of starvation resulted in glycogen deposition in all muscles examined (white, red and mixed quadriceps, soleus and diaphragm) to levels higher than those in the fed state. Although the early phase of re-feeding was associated with increases in glucose 6-phosphate levels in all muscles, there was no accompanying increase in the fractional velocity of glycogen synthase except in the white quadriceps muscle. This finding, together with the observation that the fractional velocity of glycogen synthase in most muscles was already high in the starved state, suggests that in the initial phase of glycogen deposition the phosphorylation state of the enzyme may be adequate to support net glycogen synthesis. In the later phase of re-feeding, the progressive decrease in the fractional velocity of glycogen synthase in association with a decrease in the rate of glycogen deposition suggests that glycogen synthesis is controlled primarily by changes in the phosphorylation state of glycogen synthase. In conclusion, this study suggests that there is a temporal shift in the site of control of glycogen synthesis as glycogen deposition progresses during re-feeding after starvation.


Transcriptional and epi-transcriptional dynamics of SARS-CoV-2 during cellular infection.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses subgenomic RNA (sgRNA) to produce viral proteins for replication and immune evasion. We apply long-read RNA and cDNA sequencing to in vitro human and primate infection models to study transcriptional dynamics. Transcription-regulating sequence (TRS)-dependent sgRNA upregulates earlier in infection than TRS-independent sgRNA. An abundant class of TRS-independent sgRNA consisting of a portion of open reading frame 1ab (ORF1ab) containing nsp1 joins to ORF10, and the 3' untranslated region (UTR) upregulates at 48 h post-infection in human cell lines. We identify double-junction sgRNA containing both TRS-dependent and -independent junctions. We find multiple sites at which the SARS-CoV-2 genome is consistently more modified than sgRNA and that sgRNA modifications are stable across transcript clusters, host cells, and time since infection. Our work highlights the dynamic nature of the SARS-CoV-2 transcriptome during its replication cycle.


A Community Engagement Advisory Board as a strategy to improve research engagement and build institutional capacity for community-engaged research.
Community engagement is deemed as critical to the success of the CTSA program. In 2009, to improve research engagement and build capacity for community-engaged research across the translational spectrum, the Center for Clinical and Translational Science at the University of Illinois at Chicago created a Community Engagement Advisory Board (CEAB). Here, we report results of our ongoing evaluation efforts. CEAB activities are evaluated using mixed methods. Annual CEAB evaluation surveys were completed from 2010 to 2016 (n=106 respondents). In 2014, two 90-minute focus groups were conducted with a subset of recent CEAB members (n=19). Survey data suggest respondents perceive their consultations to be helpful in improving the capacity of researchers (90%) and the quality of research projects (80%). Further, CEAB members perceive themselves to have personally benefitted from their involvement including obtaining new knowledge (84%), expansion of their networks (76%), and forming new community linkages (51%). Results of the qualitative data were consistent with survey data. Our CEAB has improved research engagement and developed institutional capacity to conduct community-engaged research in several ways. Our findings can inform the establishment or enhancement of community engagement services for CTSA-affiliated researchers and community partners.


Incidence and circumstances of falls among community-dwelling ambulatory stroke survivors: A prospective study.
To elucidate the incidences and circumstances of falls and fall-related injuries, and to explore the physical characteristics of community-dwelling ambulatory stroke survivors who experienced falls. A total of 144 community-dwelling ambulatory survivors of hemiparetic stroke (mean age 68.0 years [SD 10.4 years]) who were undergoing rehabilitation in an adult daycare center participated in this prospective study. The mean duration from stroke onset was 5.21 years (SD 3.15 years). The occurrence of falls was collected for 1 year with a fall diary. The incidence rates of falls and fall-related injuries, and the detailed circumstances of falls were descriptively analyzed. The characteristics of fallers were explored by comparing background information, motor impairments and results of physical function tests, including the 10-m walk test, Timed Up and Go test and five-times-sit-to-stand test, between fallers and non-fallers. The incidence rates of falls and fall-related fractures were 0.88 per person-year and 2.8 per 100 person-years, respectively. Falls occurred more frequently during daytime and in winter. Falls were caused most often by losing balance while walking indoors, especially on the way to the toilet. After falling, 34.1% of individuals who fell could not stand up by themselves. The time of the five-times-sit-to-stand test was significantly longer in fallers than in non-fallers (P < 0.05). The incidence rate of falls was high among community-dwelling ambulatory survivors of hemiparetic stroke. Appropriate approaches, including mastering the skills to cope with falling, are required, especially for individuals with reduced lower limb muscle strength. Geriatr Gerontol Int 2019; 19: 240-244.


COVID-19 influences on US recreational angler behavior.
Recreational angling in the United States (US) is largely a personal hobby that scales up to a multibillion-dollar economic activity. Given dramatic changes to personal decisions and behaviors resulting from the COVID-19 pandemic, we surveyed recreational anglers across the US to understand how the pandemic may have affected their fishing motivations and subsequent activities. Nearly a quarter million anglers from 10 US states were invited to participate in the survey, and almost 18,000 responded. Anglers reported numerous effects of the pandemic, including fishing access restrictions. Despite these barriers, we found that the amount of fishing in the spring of 2020 was significantly greater-by about 0.2 trips per angler-than in non-pandemic springs. Increased fishing is likely associated with our result that most respondents considered recreational angling to be a COVID-19 safe activity. Nearly a third of anglers reported changing their motivation for fishing during the pandemic, with stress relief being more popular during the pandemic than before. Driven partly by the perceived safety of social fishtancing, recreational angling remained a popular activity for many US anglers during spring 2020.


[Disturbances in the digestive tract of Ips sexdentatus (Insecta: Scolitidae) induced by Parasitorhabditis ipsophila (Nematoda: Rhabditidae)].
The histological study of the digestive tract in Ips sexdentatus parasitized by P. ipsophila showed major destruction of the microvillosities as well as vacuolization of the epithelial cells in the terminal part of the mesenteron. No damage could be observed in the hind gut nor during low contamination. Concurrently, the biochemical study indicated a lower amount of proteins in the alimentary bolus of parasitized insects along with a higher amount of proteins in the intestinal wall. Damage seemed chiefly mechanical and accounted for the disorders previously observed in populations. The apparent contradiction between the magnitude of damage to the intestinal epithelium and the mild effects of parasitism on host populations might be explained by the preferential location of nematodes in the terminal part of the mesenteron and the proximal part of the hind gut.


EBP50 is a key molecule for the Schwann cell-axon interaction in peripheral nerves.
Peripheral nerve injury disrupts the Schwann cell-axon interaction and the cellular communication between them. The peripheral nervous system has immense potential for regeneration extensively due to the innate plastic potential of Schwann cells (SCs) that allows SCs to interact with the injured axons and exert specific repair functions essential for peripheral nerve regeneration. In this study, we show that EBP50 is essential for the repair function of SCs and regeneration following nerve injury. The increased expression of EBP50 in the injured sciatic nerve of control mice suggested a significant role in regeneration. The ablation of EBP50 in mice resulted in delayed nerve repair, recovery of behavioral function, and remyelination following nerve injury. EBP50 deficiency led to deficits in SC functions, including proliferation, migration, cytoskeleton dynamics, and axon interactions. The adeno-associated virus (AAV)-mediated local expression of EBP50 improved SCs migration, functional recovery, and remyelination. ErbB2-related proteins were not differentially expressed in EBP50-deficient sciatic nerves following injury. EBP50 binds and stabilizes ErbB2 and activates the repair functions to promote regeneration. Thus, we identified EBP50 as a potent SC protein that can enhance the regeneration and functional recovery driven by NRG1-ErbB2 signaling, as well as a novel regeneration modulator capable of potential therapeutic effects.


Analysis of effect of non-steroidal anti-inflammatory drugs on teeth and oral tissues during orthodontic treatment. Report based on literature review.
In view of high availability and diversity of non-steroidal anti-inflammatory drugs (NSAIDs) on Polish market it is important for orthodontists to be aware of NSAID effect on the range of orthodontic tooth movement as well as the risk of root resorption in the moved teeth and other adverse effects, which might occur within oral cavity. The disadvantages of NSAID non-selective inhibition of COX include common oral inflammatory conditions, gingival bleeding, and disturbances of salivary secretion. Both, the selective and non-selective COX inhibitors, meloxicam excluded, used to alleviate the pain of orthodontic tooth movement, impede the movement of teeth. Paracetamol, explicitly indicated by most authors as the safest NSAID, seems to be the drug of choice in view of no influence on the range of tooth movement, the risk of root resorption or other adverse effects within oral cavity.


Prognostic models based on postoperative circulating tumor cells can predict poor tumor recurrence-free survival in patients with stage II-III colorectal cancer.
Background: It is urgent to develop robust prognostic biomarkers for non-metastatic colorectal cancer (CRC) patients undergoing surgery. The current study aimed to explore and compare the clinical significance of preoperative and postoperative blood tumor biomarkers including circulating tumor cells (CTCs), and develop prognostic models based on tumor biomarkers in patients with stage II-III CRC receiving surgery. Methods: A prospective study was performed to enroll 130 patients with stage II-III CRC receiving surgery between January 2015 and December 2017. Preoperative and postoperative blood tumor biomarkers including CTCs were detected and their prognostic value in predicting tumor recurrence-free survival (RFS) in stage II-III CRC were identified by Kaplan-Meier curves and Cox proportional hazard regression models. Results: CTCs counts within three postoperative days were significantly higher than preoperative CTCs (pre-CTCs). No significant association of pre-CTCs with clinical characteristics and tumor biomarkers was observed while positive postoperative CTCs (post-CTCs) were associated with female, older onset age, high TNM stage, tumor recurrence, and preoperative CEA. Kaplan-Meier curve with log-rank test and univariate Cox proportional hazard regression analysis suggested high N stage, TNM stage, positive pre-carbohydrate antigen (CA) 125, pre-CA19-9, post-CA125, post-CA19-9, post-CA72-4, post-carcinoembryonic antigen (CEA), and post-CTCs were correlated with poor RFS. In multivariate analysis, only TNM stage (adjusted HR=3.786, 95% CI=1.330-10.780; P=0.013), post-CA72-4 (adjusted HR=5.675, 95% CI=2.064-15.604; P=0.001), and post-CTCs (adjusted HR=2.739, 95% CI=1.042-7.200; P=0.041) were significantly correlated with poor RFS. We then developed prognostic models combining post-CTCs and post-CA72-4 with TNM stage or not to stratify the patients into different risk groups. These prognostic models exert a similar good performance in predicting tumor RFS in stage II-III CRC patients. Conclusions: Postoperative CTCs were prior to preoperative CTCs in predicting tumor recurrence survival in non-metastatic CRC patients undergoing surgery. We also developed CTCs-based prognostic models to predict tumor recurrence in stage II-III CRC, which might be used to identify the patients with high risk of recurrence and guide aggressive treatment to improve the clinical outcomes of those patients.


Role of host genetics in fibrosis.
Fibrosis can occur in tissues in response to a variety of stimuli. Following tissue injury, cells undergo transformation or activation from a quiescent to an activated state resulting in tissue remodelling. The fibrogenic process creates a tissue environment that allows inflammatory and matrix-producing cells to invade and proliferate. While this process is important for normal wound healing, chronicity can lead to impaired tissue structure and function.This review examines the major factors involved in transforming or activating tissues towards fibrosis. The role of genetic variation within individuals affected by fibrosis has not been well described and it is in this context that we have examined the mediators of remodelling, including transforming growth factor-beta, T helper 2 cytokines and matrix metalloproteinases.Finally we examine the role of Toll-like receptors in fibrosis. The inflammatory phenotype that precedes fibrosis has been associated with Toll-like receptor activation. This is particularly important when considering gastrointestinal and hepatic disease, where inappropriate Toll-like receptor signalling, in response to the local microbe-rich environment, is thought to play an important role.


Weekly and seasonal changes of intraocular pressure measured with an implanted intraocular telemetry sensor.
To better understand seasonal and weekday intraocular pressure (IOP) variations, long-term daily IOP measurements were assessed in patients with glaucoma using an intraocular telemetric sensor. This prospective, open-label, multicentre observational study analysed the IOP variation patterns in 22 eyes of 22 patients with primary open-angle glaucoma (67.8±6.8 years, 36.4% female) who had undergone placement of an intraocular telemetric sensor at the time of cataract surgery. The telemetric system combines an implantable IOP sensor with a hand-held reading device. Patients were instructed to self-measure their IOP as often as desired, but at least four times daily. Analysis of variance and Tukey multiple-comparison correction were used to assess the statistical significance of average and peak IOP variations between individual weekdays and months. Each enrolled patient recorded daily IOP measurements for an average duration of 721 days. On average, IOPs were highest on Wednesdays and lowest on Fridays (p=0.002). There were significant variations of IOP throughout the year, and IOP showed a seasonal pattern. Between mid-winter (December-January) and mid-summer months, there was a reduction in mean IOP of 8.1% (-1.55 mm Hg, p<0.05). This study confirms previously observed seasonal variations of IOP. IOP was significantly higher in winter compared with summer months. Moreover, IOP was lower on Friday than on other days. The explanation for these results is not known.


Enhanced optical forces in 2D hybrid and plasmonic waveguides.
We investigate the optical gradient force in 2D hybrid and plasmonic waveguides. By comparing with conventional dielectric waveguides, we show that the optical force can be enhanced by at least 1 order of magnitude in the hybrid and plasmonic waveguides due to strongly enhanced optical fields at the waveguide surfaces. We compare coupled plasmonic waveguides with different geometries, including rectangular, circular, and triangular cross sections and find that the rectangular waveguides provide the strongest force. We also show that the plasmonic enhancement is nonresonant and thus can be used for a broad range of wavelengths.


The nature of the catalytic domain of 2'-5'-oligoadenylate synthetases.
2'-5'-Oligoadenylate (2-5(A)) synthetases are a family of interferon-induced enzymes that are activated by double-stranded RNA. To understand why, unlike other DNA and RNA polymerases, they catalyze 2'-5' instead of 3'-5' phosphodiester bond formation, we used molecular modeling to compare the structure of the catalytic domain of DNA polymerase beta (pol beta) to that of a region of the P69 isozyme of 2-5(A) synthetase. Although the primary sequence identity is low, like pol beta, P69 can assume an alphabetabetaalphabetabetabeta structure in this region. Moreover, mutation of the three Asp residues of P69, which correspond to the three catalytic site Asp residues of pol beta, inactivated the enzyme without affecting its substrate and activator binding capacity, providing further credence to the concept that this region is the catalytic domain of P69. This domain is highly conserved among all 2-5(A) synthetase isozymes. Biochemical and mutational studies demonstrated that dimerization of the P69 protein is required for its enzyme activity. However, a dimer containing a wild type subunit and an inactive catalytic domain mutant subunit was also active. The rate of catalysis of the heterodimer was half of that of the wild type homodimer, although the two proteins bound double-stranded RNA and ATP equally well.


Biomechanical factors in tissue engineered meniscal repair.
Damage to the meniscus after trauma or injury is associated with detrimental changes in joint function that can lead to pain, disability, and degenerative joint changes. Recently, tissue engineering strategies for meniscal repair have been suggested including using biocompatible grafts as a substrate for regeneration, and cellular supplementation to promote remodeling and healing. Little is known, however, about the contributions of these novel repair strategies to restoration of normal meniscal function. Biomechanical factors play a role in the design and synthesis of tissue engineered biomaterials and bioreactors, and also are important for evaluating the efficacy of these new strategies for restoring normal meniscal function. In this report, an overview is presented of biomechanical factors that are critical to meniscal function followed by a review of biomechanical considerations for the design and evaluation of tissue engineered strategies for meniscal repair. Recommendations for future study of biomechanical factors in tissue engineered meniscal repair also are provided.


The association of keratoconus with immune disorders.
To evaluate the association between keratoconus (KC) and immune disorders (IDs). A retrospective observational case-control study of all the members in the Central District of Clalit Health Services in Israel who were diagnosed to have KC (years 2000-2007; n = 426) and 1704 age- and gender-matched controls. We calculated the prevalence of the following IDs: rheumatoid arthritis, ulcerative colitis, arthropathy, amyloidosis, systemic lupus erythematosus, celiac disease, multiple sclerosis, myasthenia gravis, polymyalgia rheumatica, idiopathic thrombocytopenic purpura, Crohn disease, Hashimoto thyroiditis, autoimmune hepatitis, irritable bowel syndrome, asthma, and environmental allergy. The odds ratio (OR) of having IDs among patients with KC was compared with controls. The association between KC and the following IDs was statistically significant: rheumatoid arthritis [OR = 8.1; 95% (confidence interval) CI: 1.5-44.2], ulcerative colitis (OR = 12.1; CI: 1.3-116), autoimmune chronic active hepatitis (OR = 6; CI: 1.01-36), Hashimoto thyroiditis (OR = 2.0; CI: 1.2-3.3), arthropathy (OR = 1.4; CI: 1.1-1.8), asthma (OR = 2.1; CI: 1.4-3.2), environmental allergy (OR = 1.3; CI: 1.02-1.75), and irritable bowel syndrome (OR = 5; CI: 2.1-12.1). Two autoimmune diseases, multiple sclerosis (OR = 2; CI: 0.2-22) and Crohn disease (OR = 1.6; CI: 0.3-8.3), were more prevalent among patients with KC but did not reach statistical significance. Some strong associations between KC and several immune conditions of autoimmune diseases and allergic IDs may point to the role of the immune system in the pathogenesis of KC.


Heterotypic reactions in a radioimmunoassay for coxsackie B virus specific IgM.
IgM antibody capture radioimmunoassays were developed to detect coxsackie virus B1-B5 specific IgM. Specific IgM was detected in sera from all patients with coxsackie B virus infections proved by isolation; however, sera from 13/32 patients with rising neutralising antibody titres were negative in the assay. Frequent heterotypic responses were seen among the positive sera. Thirty seven patients with other enterovirus infections were also studied, and sera from 15 of these patients reacted in the assay, showing that heterotypic coxsackie B IgM responses occur not only in coxsackie B virus infections but also in other enterovirus infections.


Elevated A-to-I RNA editing in COVID-19 infected individuals.
Given the current status of coronavirus disease 2019 (COVID-19) as a global pandemic, it is of high priority to gain a deeper understanding of the disease's development and how the virus impacts its host. Adenosine (A)-to-Inosine (I) RNA editing is a post-transcriptional modification, catalyzed by the ADAR family of enzymes, that can be considered part of the inherent cellular defense mechanism as it affects the innate immune response in a complex manner. It was previously reported that various viruses could interact with the host's ADAR enzymes, resulting in epigenetic changes both to the virus and the host. Here, we analyze RNA-seq of nasopharyngeal swab specimens as well as whole-blood samples of COVID-19 infected individuals and show a significant elevation in the global RNA editing activity in COVID-19 compared to healthy controls. We also detect specific coding sites that exhibit higher editing activity. We further show that the increment in editing activity during the disease is temporary and returns to baseline shortly after the symptomatic period. These significant epigenetic changes may contribute to the immune system response and affect adverse outcomes seen in post-viral cases.


Validity and reliability of the Self-Care Activities Screening Scale (SASS-14) during COVID-19 lockdown.
In a context where there is no treatment for the current COVID-19 virus, the combination of self-care behaviours together with confinement, are strategies to decrease the risk of contagion and remain healthy. However, there are no self-care measures to screen self-care activities in general population and which, could be briefly in a lockdown situation. This research aims to build and validate a psychometric tool to screen self-care activities in general population. Firstly, an exploratory factor analysis was performed in a sample of 226 participants to discover the underlying factorial structure and to reduce the number of items in the original tool into a significant pool of items related to self-care. Later a confirmatory factor analyses were performed in a new sample of 261 participants to test for the fit and goodness of factor solutions. Internal validity, reliability, and convergent validity between its score with perceived stress and psychological well-being measures were examined on this sample. The exploratory analyses suggested a four-factor solution, corresponding to health consciousness, nutrition and physical activity, sleep, and intra-personal and inter-personal coping skills (14 items). Then, the four-factor structure was confirmed as the best model fit for self-care activities. The tool demonstrated good reliability, predictive validity of individuals' perception of coping with COVID-19 lockdown, and convergent validity with well-being and perceived stress. This screening tool could be helpful to address future evaluations and interventions to promote healthy behaviours. Likewise, this tool can be targeted to specific population self-care's needs during a scalable situation.


Association between musculoskeletal pain in Japanese construction workers and job, age, alcohol consumption, and smoking.
A cross-sectional epidemiologic study was conducted to determine the prevalence of self-reported musculoskeletal pain (MSP) in construction workers and identify associations between MSP and individual factors (i.e., job, age, alcohol consumption, and smoking). The prevalence of total hand/arm pain (T-HAP), total shoulder pain (T-SP), and total low-back pain (T-LBP) was 28.4%, 28.7%, and 53.2%, respectively. Risk factors for total pain and for relatively severe pain in the hand/arm (RS-HAP), shoulder (RS-SP), and low-back (RS-LBP) were estimated by multiple logistic regression analysis. The results showed that musculoskeletal pain was significantly associated with age, and that the odds ratios (ORs) for relatively severe musculoskeletal pain increased almost linearly with age. Regarding job, compared with architects whose work is presumed to be sedentary, almost all ORs for T-HAP, T-SP, and T-LBP for non-sedentary construction jobs were significantly high. Current smokers of 20 cigarettes a day or more had significantly higher ORs for RS-HAP and RS-LBP than "never smokers". We suppose that 1) total and relatively severe pain were associated with age, 2) non-sedentary work was at higher risk of total MSP than sedentary work, and 3) heavy smoking contributed to RS-LBP.


Effects of foliar boron application on seed composition, cell wall boron, and seed δ(15)N and δ(13)C isotopes in water-stressed soybean plants.
Limited information is available on the effects of foliar boron (B) application on soybean seed composition. The objective of this research was to investigate the effects of foliar B on seed composition (protein, oil, fatty acids, and sugars). Our hypothesis was that since B is involved in nitrogen and carbon metabolism, it may impact seed composition. A repeated greenhouse experiment was conducted where half of the soybean plants was exposed to water stress (WS) and the other half was well-watered. Foliar boron (FB) in the form of boric acid was applied twice at a rate of 1.1 kg ha(-1). The first application was during flowering stage, and the second application was during seed-fill stage. Treatments were water stressed plants with no FB (WS-B); water stressed plants with FB (WS+B); watered plants without FB (W-B), and watered plants with FB (W+B). The treatment W-B was used as a control. Comparing with WS-B plants, B concentration was the highest in leaves and seed of W+B plants (84% increase in leaves and 73% in seed). Seeds of W+B plants had higher protein (11% increase), oleic acid (27% increase), sucrose (up to 40% increase), glucose, and fructose comparing with W-B. However, seed stachyose concentrations increased by 43% in WS-B plants seed compared with W-B plants. Cell wall (structural) B concentration in leaves was higher in all plants under water stress, especially in WS-B plants where the percentage of cell wall B reached up to 90%. Water stress changed seed δ(15)N and δ(13)C values in both B applied and non-B applied plants, indicating possible effects on nitrogen and carbon metabolism. This research demonstrated that FB increased B accumulation in leaves and seed, and altered seed composition of well-watered and water stressed plants, indicating a possible involvement of B in seed protein, and oleic and linolenic fatty acids. Further research is needed to explain mechanisms of B involvement in seed protein and fatty acids.


Outbreak investigation for toxigenic Corynebacterium diphtheriae wound infections in refugees from Northeast Africa and Syria in Switzerland and Germany by whole genome sequencing.
Toxigenic Corynebacterium diphtheriae is an important and potentially fatal threat to patients and public health. During the current dramatic influx of refugees into Europe, our objective was to use whole genome sequencing for the characterization of a suspected outbreak of C. diphtheriae wound infections among refugees. After conventional culture, we identified C. diphtheriae using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and investigated toxigenicity by PCR. Whole genome sequencing was performed on a MiSeq Illumina with >70×coverage, 2×250 bp read length, and mapping against a reference genome. Twenty cases of cutaneous C. diphtheriae in refugees from East African countries and Syria identified between April and August 2015 were included. Patients presented with wound infections shortly after arrival in Switzerland and Germany. Toxin production was detected in 9/20 (45%) isolates. Whole genome sequencing-based typing revealed relatedness between isolates using neighbour-joining algorithms. We detected three separate clusters among epidemiologically related refugees. Although the isolates within a cluster showed strong relatedness, isolates differed by >50 nucleotide polymorphisms. Toxigenic C. diphtheriae associated wound infections are currently observed more frequently in Europe, due to refugees travelling under poor hygienic conditions. Close genetic relatedness of C. diphtheriae isolates from 20 refugees with wound infections indicates likely transmission between patients. However, the diversity within each cluster and phylogenetic time-tree analysis suggest that transmissions happened several months ago, most likely outside Europe. Whole genome sequencing offers the potential to describe outbreaks at very high resolution and is a helpful tool in infection tracking and identification of transmission routes.


Effect of elevated environmental temperature on the antibody response of mice to Trypanosoma cruzi during the acute phase of infection.
When held at 36 degrees C, Trypanosoma cruzi-infected C3H mice survive an otherwise lethal infection with significantly decreased parasitemia levels and enhanced immune responsiveness. Treatment of T. cruzi-infected mice with the immunosuppressive agent cyclophosphamide indicated that the positive effects of increased environmental temperature were primarily due to enhancement of immunity. A parasite-specific, enzyme-linked immunosorbent assay and immunoblot analysis were used to examine the effect of elevated environmental temperature on the production of anti-T. cruzi antibodies. Both the reactivity and diversity of anti-T. cruzi antibodies were found to be lower in infected mice held at 36 degrees C than in infected mice held at room temperature. However, reactivity and diversity could be enhanced by vaccination with culture forms of the parasite.


Dominant atopy risk mutations identified by mouse forward genetic analysis.
Atopy, the overall tendency to become sensitized to an allergen, is heritable but seldom ascribed to mutations within specific genes. Atopic individuals develop abnormally elevated IgE responses to immunization with potential allergens. To gain insight into the genetic causes of atopy, we carried out a forward genetic screen for atopy in mice. We screened mice carrying homozygous and heterozygous N-ethyl-N-nitrosourea (ENU)-induced germline mutations for aberrant antigen-specific IgE and IgG1 production in response to immunization with the model allergen papain. Candidate genes were validated by independent gene mutation. Of 31 candidate genes selected for investigation, the effects of mutations in 23 genes on papain-specific IgE or IgG1 were verified. Among the 20 verified genes influencing the IgE response, eight were necessary for the response, while 12 repressed IgE. Nine genes were not previously implicated in the IgE response. Fifteen genes encoded proteins contributing to IgE class switch recombination or B-cell receptor signaling. The precise roles of the five remaining genes (Flcn, Map1lc3b, Me2, Prkd2, and Scarb2) remain to be determined. Loss-of-function mutations in nine of the 12 genes limiting the IgE response were dominant or semi-dominant for the IgE phenotype but did not cause immunodeficiency in the heterozygous state. Using damaging allele frequencies for the corresponding human genes and in silico simulations (Monte Carlo) of undiscovered atopy mutations, we estimated the percentage of humans with heterozygous atopy risk mutations. Up to 37% of individuals may be heterozygous carriers for at least one dominant atopy risk mutation.


Mitochondrial responses towards intermittent heat shocks in the eastern oyster, Crassostrea virginica.
Frequent heat waves caused by climate change can give rise to physiological stress in many animals, particularly in sessile ectotherms such as bivalves. Most studies characterizing thermal stress in bivalves focus on evaluating the responses to a single stress event. This does not accurately reflect the reality faced by bivalves, which are often subject to intermittent heat waves. Here, we investigated the effect of intermittent heat stress on mitochondrial functions of the eastern oyster, Crassostrea virginica, which play a key role in setting the thermal tolerance of ectotherms. Specifically, we measured changes in mitochondrial oxygen consumption and H2O2 emission rates before, during and after intermittent 7.5°C heat shocks in oysters acclimated to 15 and 22.5°C. Our results showed that oxygen consumption was impaired following the first heat shock at both acclimation temperatures. After the second heat shock, results for oysters acclimated to 15°C indicated a return to normal. However, oysters acclimated to 22.5°C struggled more with the compounding effects of intermittent heat shocks as denoted by an increased contribution of FAD-linked substrates to mitochondrial respiration as well as high levels of H2O2 emission rates. However, both acclimated populations showed signs of potential recovery 10 days after the second heat shock, reflecting a surprising resilience to heat waves by C. virginica. Thus, this study highlights the important role of acclimation in the oyster's capacity to weather intermittent heat shock.


Pesticide exposure affects flight dynamics and reduces flight endurance in bumblebees.
The emergence of agricultural land use change creates a number of challenges that insect pollinators, such as eusocial bees, must overcome. Resultant fragmentation and loss of suitable foraging habitats, combined with pesticide exposure, may increase demands on foraging, specifically the ability to collect or reach sufficient resources under such stress. Understanding effects that pesticides have on flight performance is therefore vital if we are to assess colony success in these changing landscapes. Neonicotinoids are one of the most widely used classes of pesticide across the globe, and exposure to bees has been associated with reduced foraging efficiency and homing ability. One explanation for these effects could be that elements of flight are being affected, but apart from a couple of studies on the honeybee (Apis mellifera), this has scarcely been tested. Here, we used flight mills to investigate how exposure to a field realistic (10 ppb) acute dose of imidacloprid affected flight performance of a wild insect pollinator-the bumblebee, Bombus terrestris audax. Intriguingly, observations showed exposed workers flew at a significantly higher velocity over the first ¾ km of flight. This apparent hyperactivity, however, may have a cost because exposed workers showed reduced flight distance and duration to around a third of what control workers were capable of achieving. Given that bumblebees are central place foragers, impairment to flight endurance could translate to a decline in potential forage area, decreasing the abundance, diversity, and nutritional quality of available food, while potentially diminishing pollination service capabilities.


Tumour markers in prostate cancer II: diagnostic and prognostic cellular biomarkers.
The main goal of prostate cancer tissue biomarkers is to improve diagnostic and prognostic accuracy. A particularly important question is whether the cancer needs immediate treatment or if treatment can be deferred. It is highly unlikely that a single biomarker that provides comprehensive prognostic information about a newly diagnosed prostate cancer will be forthcoming. Despite extensive research efforts, very few biomarkers of prostate cancer have been successfully implemented into clinical practice today. This can be partly explained by a lack of standardised methods for performance and interpretation of immunohistochemistry, but also by poor study design with insufficient biomaterial or inappropriate statistical analysis. Also appropriate cohorts to test prostate cancer biomarkers do not exist. It must be kept in mind that unsuccessful integration of new biomarkers in nomograms can also be explained by the good performance of the clinical and pathological base model with serum PSA as the only independent biomarker. A new biomarker must be powerful enough to improve this prediction model and not merely replace. In this report, we focus on diagnostic and prognostic cellular biomarkers in prostate cancer, recent advances and future aspects by reviewing currently available literature. Similar to other malignancies, the proliferation marker Ki-67 seems to be a prognostic tissue biomarker and a strong candidate for integration in prediction models. Circulating tumour cells are promising markers of response to treatments in patients with metastatic disease. Important technical advances together with histological techniques of antibody or probes conjugated with different fluorophores will certainly improve standardisation and make immunohistochemical biomarker research more reliable and precise in the future. Cellular biomarker studies are also expected to change in the future towards a complexed individualised profiling of human tumours with integrative analysis using different technologies, genome-wide scanning and expression profiling.


Structured, nurse-led ward rounds to improve interprofessional communication and optimize care of vascular surgery patients: a best practice implementation project.
Ward rounds are crucial inpatient activities during which patients' conditions are discussed. Team-based models such as nurse-led ward rounds (NLWRs) have been conceptualized and trialled, with positive results. An evidence-based quality improvement pilot project to introduce NLWRs was implemented at a cardiovascular medical-surgical unit in a Singapore tertiary hospital. The JBI Evidence Implementation Framework was used to guide the project. The evidence-based NLWR format incorporated stakeholder feedback on NLWR frequency, preparation, coordination, and content. Baseline and 6-month post-implementation audits were carried out. The 4 audit criteria improved from baseline, reaching 100% compliance for criteria 1, 2, and 3 associated with interprofessional communication and collaboration. An improvement from baseline (30% to 46.7%) was also observed for criterion 4 on patient involvement during medical ward rounds. Moreover, there were improvements in clinical outcome data such as patient hospitalization length, "best medical therapy" rates, and inpatient complications. A statistically significant improvement in nurses' confidence to lead discussions during medical rounds was also observed ( p = 0.026). This project promoted greater compliance with NLWR criteria through audit and feedback cycles and the contextualization of implementation strategies. A well-supported program that prepares nurses for interprofessional communication also improves nurses' confidence in team communication, bolstering their ability to provide high-quality patient care.


Quantification of non-structural carbohydrates in different tissues of trees with diffuse reflectance spectroscopy: Is there a benefit from a fusion of near- and mid-infrared data?
Understanding the role of non-structural carbohydrates (NSC) in tree-level carbon cycling crucially depends on the availability of NSC data in a sufficient temporal resolution covering extreme conditions and seasonal peaks or declines. Chemical analytical methods should therefore get complemented by less extensive retrieval methods. To this end, we explored the potential of diffuse reflectance spectroscopy for estimating NSC contents at a set of 180 samples taken from leaves, roots, stems and branches of different tree species in different biogeographic regions. Multiple randomized partitioning in calibration and validation data were performed with near-infrared (NIR) and mid-infrared (MIR) as well as combined data. With derivative spectra, NIR markedly outperformed MIR data for NSC estimation; mean RMSE for outer validation samples equalled 2.58 (in % of dry matter) compared to 2.90, r2 was 0.64 compared to 0.52. We found complementary information related to NSC in both spectral domains, so that a combination with high-level data fusion (model averaging) increased accuracy (RMSE decreased to 2.19, r2 equalled 0.72). Spectral variable selection with the CARS algorithm further improved results slightly (RMSE = 1.97, r2 = 0.78). On the level of tissue types, we found a marked differentiation concerning the appropriateness of datasets and approaches. High-level data fusion was successful for leaves, NIR data (together with CARS) provided the best results for wooden tissues. This suggests further studies with a greater number of samples per tissue type but only for selected (main) tree species to finally judge the sensitivities of diffuse reflectance spectroscopy (NIR, MIR) for NSC retrieval.


Enhanced self-cleaning, antibacterial and UV protection properties of nano TiO2 treated textile through enzymatic pretreatment.
Textile materials can be treated with some enzymes to improve their functionality. The usual enzymatic treatment hydrolyzes the textile surfaces that leads to increase the functional groups. Here, the polyester/wool fabric as a blend of fibers fabric was selected and treated with the two different types of enzymes to increase the surface activity with a propose of higher nano-TiO(2) adsorption. The fabric was first treated with proteases and lipases to hydrolyze the wool and the polyester surfaces, respectively. It has been then dipped into an ultrasound bath containing nano TiO(2) and cross-linking agent followed by curing. The cross-linking agent, butane tetracarboxylic acid (BTCA), also assisted to enhance the nano-particles adsorption and stabilization on the fabric surface. The self-cleaning properties of the fabrics were examined through evaluating the color removal from the stained fabric with Acid Blue 113. The antibacterial properties were determined by reduction growth of a Gram-negative bacteria E. coli. and the UV protection was assessed by UV-reflectance spectrum. The SEM pictures and EDX spectrums of some samples were also reported.


Innovative analysis of diazepam, zolpidem and their main metabolites in human urine by micelle-to-solvent stacking in capillary electrophoresis.
Diazepam and zolpidem are the most widely used medications for managing insomnia. However, significant concerns regarding the potential risks of misuse and abuse problems arose in many literatures. While urine analysis is a valuable diagnostic tool, a challenge arises from the fact that some parent drugs may remain undetectable in urine. This necessitates concurrent monitoring of their metabolites. Here, we described an innovative on-line sample preconcentration technique known as micelle to solvent stacking (MSS) for the analysis of diazepam, zolpidem, and their main metabolites in urine. Several key parameters warrant further discussion to optimize the MSS model, enhancing its performance in terms of sensitivity and resolution. After optimizing the conditions, we conducted a validation test, achieving high correlation coefficients (greater than 0.9977) for intra-day and inter-day regression lines. Additionally, both the relative standard deviation (RSD) and relative error (RE) remained below 6.10% and 12.55%, respectively. The limits of detection (LODs, S/N = 3) for all five analytes ranged from 2.0 to 56 ng/mL. Compared to the conventional capillary zone electrophoresis method, this new approach exhibited remarkable sensitivity enhancements, ranging from 123 to 235-fold. Upon applying this method to actual urine samples from patients, we successfully detected nordiazepam, zolpidem, and its metabolites. This simple and sensitive approach has promising applications in supporting patient medication safety and bolstering forensic investigations.


Effects of boar contact and housing conditions on estrus expression in weaned sows.
Our objective was to study the effects of housing conditions and the amount of boar contact in a protocol for estrus detection on estrus detection rate, timing of onset of estrus, duration of estrus, and timing of ovulation. After weaning, 130 multiparous sows were assigned to three treatments: HI, in which 52 sows were housed individually in crates and received a high amount of boar contact during estrus detection; HG, in which 52 sows were housed in groups and received a high amount of boar contact; and NI, in which 26 sows were housed individually in crates and received a normal amount of boar contact. Estrus detection was performed every 8 h. For each treatment, the standing response to three levels of stimuli was recorded: a back pressure test (BPT) by a man (man-estrus), presence of a teaser boar (spontaneous-estrus), and BPT in the presence of a teaser boar (boar-estrus). In addition, for HI and HG, the standing response to a fourth level of stimuli was recorded: BPT in a detection-mating area, surrounded by four boar pens (DMA-estrus). To detect ovulation, ultrasonography was performed every 4 h during estrus. Of 117 sows that ovulated, 46% showed man-estrus, 56% spontaneous-estrus, 90% boar-estrus, and 97% DMA-estrus. Mean onset of man-estrus was 107 h (SD 26) after weaning, of spontaneous-estrus was 106 h (SD 22) after weaning, of boar-estrus was 99 h (SD 21) after weaning, and of DMA-estrus was 93 h (SD 22) after weaning. Duration of man-estrus was 22 h (SD 14), of spontaneous-estrus was 29 h (SD 16), of boar-estrus was 42 h (SD 20), and of DMA-estrus was 55 h (SD 18). The high amount of boar contact reduced the number of sows showing man-estrus (P < .05; 41% for HG and HI vs 68% for NI) and reduced duration of boar-estrus (P < .05; 43 h for HG and HI vs 52 h for NI). Duration of DMA-estrus for HG and HI was similar to duration of boar-estrus for NI. Onset of estrus and timing of ovulation were not affected by amount of boar contact. Group housing did not affect detection rate and duration of estrus, but it did postpone average onset of estrus by 10 h, paralleled by a postponement of ovulation. In conclusion, estrus expression is similar at the highest level of stimuli in different protocols for estrus detection. Including higher levels of stimuli in a protocol reduces estrus expression at lower levels of stimuli. This reduction indicates adaptation of sows to a given protocol for estrus detection. Group housing can delay ovulation and related behavioral estrus.


Symptom Occurrence, Severity, and Self-Care Methods by Ethnicity and Age Group Among Adults With Cancer.
To examine the relationships among cancer therapy-related symptom occurrence and severity, selected cancer-related variables, and demographic variables. Secondary purposes were to examine participants' reported symptom occurrence and severity by ethnicity and by age group and to identify self-care methods. Convenience sampling was used and included 110 adults receiving cancer treatment from a major hospital in the northeast region of the United States. A descriptive correlational design was used. Study variables were symptom occurrence and severity and selected demographic and cancer-related variables. The Therapy-Related Symptom Checklist was used to measure symptom occurrence and severity, and the Symptom Alleviation. Significant relationships were found between symptom occurrence and severity and gender, economic status, and disease stage. Feeling sluggish was the most frequently reported symptom. Oncology nurses are in an influential position to educate and manage participants' cancer therapy-related symptoms.


Automated estimation of number of implanted iodine-125 seeds for prostate brachytherapy based on two-view analysis of pelvic radiographs.
Digital pelvic radiographs are used to identify the locations of implanted iodine-125 seeds and their numbers after insertion. However, it is difficult and laborious to visually identify and count all implanted seeds on the pelvic radiographs within a short time. Therefore, our purpose in this research was to develop an automated method for estimation of the number of implanted seeds based on two-view analysis of pelvic radiographs. First, the images of the seed candidates on the pelvic image were enhanced using a difference of Gaussian filter, and were identified by binarizing the enhanced image with a threshold value determined by multiple-gray level thresholding. Second, a simple rule-base method using ten image features was applied for false positive removal. Third, the candidates for the likely number of a multiply overlapping seed region, which may include one or more seeds, were estimated by a seed area histogram analysis and calculation of the probability of the likely number of overlapping seeds. As a result, the proposed method detected 99.9% of implanted seeds with 0.71 false positives per image on average in a test for training cases, and 99.2% with 0.32 false positives in a validation test. Moreover, the number of implanted seeds was estimated correctly at an overall recognition rate of 100% in the validation test using the proposed method. Therefore, the verification time for the number of implanted seeds could be reduced by the provision of several candidates for the likely number of seeds.


Association between decreased neck circumference and impaired activities of daily living among older adults in long-term care.
Assessment interventions for the decline of activities of daily living (ADLs) in older adults are crucial, as ADL decline increases hospitalization duration and mortality risk. Decreased neck circumference may result in various physical dysfunctions, including malnutrition. However, the association between neck circumference and ADLs has not been fully clarified. This study aimed to determine the association between decreased neck circumference and ADLs in older adults requiring long-term care. The study included 152 older adults deemed to require support or care under Japan's long-term care insurance system. Neck circumference was measured just below the thyroid cartilage with a measuring tape. The Barthel index was used to evaluate ADLs, and skeletal muscle mass and nutritional status were assessed by bioelectrical impedance analysis instruments. A multivariate analysis was conducted to investigate the association between neck circumference and ADLs. Neck circumference demonstrated a significant inverse correlation with age and a significant positive correlation with body mass index, skeletal muscle mass index, phase angle, and Barthel index. In the multivariate analysis, ADLs was significantly associated with neck circumference (odds ratio [OR] = 0.51, P = 0.002) and phase angle (OR = 0.04, P < 0.001). Neck circumference is associated with age, skeletal muscle mass, and nutritional status. Furthermore, a decrease in neck circumference is suggested as an independent risk factor for ADL decline in older adults requiring long-term care. Geriatr Gerontol Int 2023; 23: 906-911.


Pediatric Baseline Patch Test Series: Pediatric Contact Dermatitis Workgroup.
Allergic contact dermatitis is a challenging diagnostic problem in children. Although epicutaneous patch testing is the diagnostic standard for confirmation of contact sensitization, it is less used in children by dermatologists treating children, pediatric dermatologists, and pediatricians, when compared with adult practitioners. The aim of the study was to create and evaluate standardization of a pediatric patch test series for children older than 6 years. We surveyed dermatologists and allergists conducting epicutaneous patch testing in children attending the 2017 American Contact Dermatitis Society meeting held in Washington, DC. This was followed by discussion of collected data and consensus review by a pediatric contact dermatitis working group at the conference. A baseline pediatric patch test panel was established through working group consensus.


Implications of Prolonged Time to Pancreaticoduodenectomy After Neoadjuvant Chemoradiation.
For patients with pancreatic adenocarcinoma (PA), the optimal time interval between neoadjuvant chemoradiation (CR) to surgical resection has not been well established. The National Cancer Database from 2006 to 2014 was queried for patients ≥18 y old diagnosed with PA who received neoadjuvant CR. Survival and short-term outcomes were compared between patients who had pancreaticoduodenectomy ≤12 wk and >12 wk after completion of CR. 1610 patients met selection criteria. Average radiation to surgery (RS) interval was 58.2 ± 39.5 d. 1419 patients had RS interval ≤12 wk (mean 47.4 d) and 191 had RS interval >12 wk (mean 138.8 d). Demographics, CA 19-9 levels, types of chemotherapy and radiation dosage were similar between the two groups. There were more patients with clinical stage III cancers in the >12 wk group than in the ≤12 wk group (33.5% versus 14%). Short-term outcomes were similar between the two groups. However, a long-term survival benefit was observed in the >12 wk group (median 25.8 versus 30.2 mo P = 0.049). An interval >12 wk was associated with significantly prolonged survival on multivariate analysis (HR: 0.80, 95% CI: 0.65-0.99; P = 0.042). Higher clinical stage and positive surgical margins were independently associated with worse survival. Surgical resection beyond 12 wk after CR for PA did not worsen short-term outcomes. Waiting may contribute to better patient selection, especially those with locally advanced tumors. In the absence of progressive disease, patients need to be continuously evaluated for surgical resection after CR.


HIV protease inhibitors selectively induce gene expression alterations associated with reduced calcium deposition in primary human osteoblasts.
HIV-infected patients are at increased risk of decreased bone mineral density. Some studies have implicated antiretroviral therapy as a contributor to the decreased bone mineral density seen in treated HIV-1 patients. In this study we explore the interactions between protease inhibitors (PI) and primary human osteoblast gene expression, highlighting a group of dysregulated genes that potentially are key factors in reducing bone formation. Runx-2 mRNA expression, calcium deposition, and alkaline phosphatase (ALP) activity decreased significantly in human osteoblast cultures after exposure to the PIs nelfinavir (NFV) and indinavir (IDV). Saquinavir (SQV), ritonavir (RTV), indinavir (IDV), or nelfinavir (NFV) exposure induced significant changes in genotypic expression as assessed by gene-chip microarray analysis. The altered genes from each group were compared to each other and a list of 8 upregulated and 13 downregulated genes only after NFV and IDV exposure was identified. This set includes TIMP-3, which has previously been demonstrated to be involved in osteoblast differentiation and extracellular matrix development processes. Silencing TIMP-3 mRNA expression using siRNA duplexes enhanced calcium deposition and ALP activity significantly, even after exposure to NFV and IDV. Our data suggest a link between reduced osteoblastic phenotype and a group of 21 altered genes following NFV and IDV treatment, and also suggest TIMP-3 may be involved in the PI-induced inhibition of osteoblast function.


Contrasts in HMO and fee-for-service performance.
This study compares various aspects of HMO performance in 10 plans with that of the fee-for-service system for the Medicaid population. Additionally, it examines utilization differences between several types of HMO's, grouped according to organization and provider payment. Four areas of behavior were studied--enrollment selectivity, utilization of services, accessibility of care, and satisfaction. The only significant difference between the two systems was in hospital utilization. Group-practice MNO's had significantly lower hospital utilization than the fee-for-service groups: foundation HMO's did not. This difference seems to indicate that capitation payment to an HMO alone is not significant enough to produce major changes in utilization and that the organized multispecialty group-practice arrangement with largely salaried physicians may be more significant. For the other variables--previous health status, ambulatory-care use (including preventive care), accessibility, and satisfaction--the two groups were remarkably similar.


Evaluation of monophosphoryl lipid A (MPL) as an adjuvant. Enhancement of the serum antibody response in mice to polysaccharide-protein conjugates by concurrent injection with MPL.
Concurrent injection of monophosphoryl lipid A (MPL) in saline or as an oil-in-water emulsion enhanced both the primary and secondary serum antibody responses to the capsular polysaccharide (CP) components of seven conjugates: the enhanced responses were Ag-specific. In contrast, MPL did not enhance the serum antibody response to five of the six unconjugated CP. MPL and trehalose dimycolate injected concurrently with the unconjugated Vi CP of Salmonella typhi (Vi) enhanced the serum antibody response to that Ag. MPL further enhanced the Vi antibody levels when injected with conjugates of this CP. The serum antibody responses to Pseudomonas aeruginosa exotoxin A, used as the carrier protein for the Staphylococcus aureus types 5 and 8 conjugates, were also enhanced by MPL. MPL in oil-in-water emulsion was generally more effective than when administered in saline.


Selective elevation of circulating CCL2/MCP1 levels in patients with longstanding post-vaccinal macrophagic myofasciitis and ASIA.
Several medical conditions sharing similar signs and symptoms may be related to immune adjuvants. These conditions described as ASIA (Autoimmune/inflammatory Syndrome Induced by Adjuvants), include a condition characterized by macrophagic myofasciitis (MMF) assessing long-term persistence of vaccine derived-alum adjuvants into macrophages at sites of previous immunization. Despite increasing data describing clinical manifestations of ASIA have been reported, biological markers are particularly lacking for their characterization and follow up. We report an extensive cytokine screening performed in serum from 44 MMF patients compared both to sex and age matched healthy controls and to patients with various types of inflammatory neuromuscular diseases. Thirty cytokines were quantified using combination of Luminex® technology and ELISA. There was significant mean increase of serum levels of the monocytechemoattractant protein 1 (CCL2/MCP-1) in MMF patients compared to healthy subjects. MMF patients showed no elevation of other cytokines. This contrasted with inflammatory patients in whom CCL2/MCP-1 serum levels were unchanged, whereas several other inflammatory cytokines were elevated (IL1β, IL5 and CCL3/MIP1α). These results suggest that CCL2 may represent a biological marker relevant to the pathophysiology of MMF rather than a non specific inflammatory marker and that it should be checked in the other syndromes constitutive of ASIA.


Uncovering the Recycling Potential of "New" WEEE in China.
Newly defined categories of WEEE have increased the types of China's regulated WEEE from 5 to 14. Identification of the amounts and valuable-resource components of the "new" WEEE generated is critical to solving the e-waste problem, for both governmental policy decisions and recycling enterprise expansions. This study first estimates and predicts China's new WEEE generation for the period of 2010-2030 using material flow analysis and the lifespan model of the Weibull distribution, then determines the amounts of valuable resources (e.g., base materials, precious metals, and rare-earth minerals) encased annually in WEEE, and their dynamic transfer from in-use stock to waste. Main findings include the following: (i) China will generate 15.5 and 28.4 million tons WEEE in 2020 and 2030, respectively, and has already overtaken the U.S. to become the world's leading producer of e-waste; (ii) among all the types of WEEE, air conditioners, desktop personal computers, refrigerators, and washing machines contribute over 70% of total WEEE by weight. The two categories of EEE-electronic devices and electrical appliances-each contribute about half of total WEEE by weight; (iii) more and more valuable resources have been transferred from in-use products to WEEE, significantly enhancing the recycling potential of WEEE from an economic perspective; and (iv) WEEE recycling potential has been evolving from ∼16 (10-22) billion US$ in 2010, to an anticipated ∼42 (26-58) billion US$ in 2020 and ∼73.4 (44.5-103.4) billion US$ by 2030. All the obtained results can improve the knowledge base for closing the loop of WEEE recycling, and contribute to governmental policy making and the recycling industry's business development.


Effect of autologous platelet-rich plasma on distraction osteogenesis in the mandible of rabbits: a morphologic and morphometric approach.
Distraction osteogenesis of the jaw is a common surgical practice in the treatment of pediatric craniofacial deformities. Autologous platelet rich plasma (PRP) has been used to increase the healing potential of bones in humans during distraction osteogenesis. This article aims to study the morphometric and morphologic parameters resulting from the effect of PRP on bone healing after mandibular distraction in rabbits. Right mandibular distraction was performed in 12 rabbits divided equally into 2 groups. PRP and physiological saline were injected, according to a defined protocol, in the callus following distraction of the experimental and control groups respectively. The rabbits were sacrificed after a consolidation period of 45 days and the mandibles were surgically removed. Bone mineral density, radiographic analysis, mechanical properties and histological features of the lengthened bones were assessed using radiographic examination, dual X-ray absorptiometry, biomechanical testing and histology. Results showed that the regenerate bone density, the amount of trabeculation in addition to the bone mineral density and mineral content, as measured by absorptiometry, were better with PRP but not significantly different between groups. Two radiographs revealed a more consistent healing in the experimental mandibles compared with erratic outcomes in corresponding controls. Two of the latter could not be subjected to any mechanical testing because the mandibular parts, connected with fibrous tissue, were separated. Consequently, the biomechanical test depicted greater maximal loads in the experimental group. The histological studies exhibited more ossification and less connective tissue fibers in the experimental group. PRP accelerated healing of mandibles in rabbits following distraction and improved their biomechanical properties. These findings have significant clinical implications on reducing the period of consolidation of the mandibles which may not be immobilized like other bones for long periods of time.


Trapped free radicals and electrons in organic glasses.
Free radicals, hydrogen atoms, and electrons produced in rigid organic glasses at sufficiently low temperatures have lifetimes of minutes to years. They can be studied by their electron spin resonance spectra and, in the case of electrons, by their optical spectra, recombination luminescence, and electrical conductivity. The decay kinetics of these reaction intermediates serve to distinguish those trapped as geminate pairs or in spurs of high concentration from those formed with random distributions. Electron spin resonance studies of relaxation times and of the spectra of radical pairs provide further evidence on geometrical distributions. The decay rates of radicals combining with reactive geminate partners are dependent on the size and shape of the radical, the temperature, and the nature of the matrix. Decay is much slower in deuterated matrices than in protiated matrices. The factors that control the physical trapping of electrons in organic glasses are under intensive investigation. There is evidence that many electrons trapped relatively weakly during irradiations at 4 degrees K deepen their traps by orientation of dipoles when the matrix is warmed; that most electrons are trapped in the field of the geminate positive ion; that in some matrices the traps have a bound excited state to which the electron can be promoted without detrapping; and that trapped electrons can tunnel to solute molecules with a higher electron affinity than the trap depth.


Ciceribacter lividus gen. nov., sp. nov., isolated from rhizosphere soil of chick pea (Cicer arietinum L.).
The taxonomic position of strain MSSRFBL1(T), isolated from chickpea rhizosphere soil from Kannivadi, India, was determined. Strain MSSRFBL1(T) formed bluish black colonies, stained Gram-negative and was motile, aerobic, capable of fixing dinitrogen, oxidase-negative and catalase-positive. Q-10 was the major respiratory quinone. Major fatty acids of strain MSSRFBL1(T) were C18 : 1ω7c and C19 : 0cycloω8c. Minor amounts of C18 : 0, C12 : 0, C14 : 0 3-OH, C18 : 0 3-OH, C16 : 0, C16 : 1ω6c/C16 : 1ω7c, C17 : 0 3-OH and C20 : 1ω7c were also present. Polar lipids included diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine, phosphatidylcholine and two unidentified glycolipids. Bacteriohopane derivatives (BHD1 and 2), diplopterol, diploptene, bishomohopanediol, adenosylhopane and 2β-methyl bacteriohopanetetrol were the major hopanoids of strain MSSRFBL1(T). The genomic DNA G+C content was 71 mol%. EzTaxon-e-based blast analysis of the 16S rRNA gene indicated the highest similarity of strain MSSRFBL1(T) to Ensifer adhaerens LMG 20216(T) (97.3 %) and other members of the genus Ensifer (<96.9 %) in the family Rhizobiaceae of the class Alphaproteobacteria. However, phylogenetic analysis based on 16S rRNA, recA, thrC and dnaK gene sequences showed distinct out-grouping from the recognized genera of the family Rhizobiaceae. Based on phenotypic, genotypic and chemotaxonomic characters, strain MSSRFBL1(T) represents a novel species in a new genus in the family Rhizobiaceae for which the name Ciceribacter lividus gen. nov., sp. nov. is proposed. The type strain of Ciceribacter lividus is MSSRFBL1(T) ( = DSM 25528(T) = KCTC 32403(T)).


Genetic variation in the upstream region of ERG and prostate cancer.
A considerable fraction of prostate cancers harbor a gene fusion between the androgen-regulated TMPRSS2 and ERG, one of the most frequently over-expressed proto-oncogenes in prostate cancer. Here, we investigated if inherited genetic variation upstream of ERG alters prostate cancer risk and survival. We genotyped 21 haplotype tagging SNPs (htSNPs) covering 123 kb of 5'UTR DNA including exon 3 of ERG in 2,760 incident prostate cancer cases and 1,647 controls from a population-based Swedish case-control study (CAPS). Individual SNPs and haplotypes were tested for association with prostate cancer risk and survival. One haplotype-'CTCGTATG' located 100 kb upstream of ERG-was associated with lethal prostate cancer (HR, 1.36; 95% CI, 1.2-1.9, p = 0.006). Carriers of the variant 'T' allele of rs2836626 were diagnosed with higher TNM-stage (p = 0.009) and had an increased risk of prostate cancer-specific death (HR = 1.3; 95% CI, 1.1-1.7, p = 0.009). However, this association did not remain statistically significant after adjusting for multiple testing. We found overall no association between ERG variation and prostate cancer risk. Genetic variation upstream of ERG may alter prostate cancer stage and ultimately prostate cancer-specific death but it is unlikely that it plays a role in prostate cancer development.


[TRPC6 mediates the enhancements of pulmonary arterial tone and intracellular Ca2+ concentration of pulmonary arterial smooth muscle cells in pulmonary hypertension rats].
Pulmonary arterial hypertension is associated with profound vascular remodeling and alterations in Ca2+ homeostasis in pulmonary arterial smooth muscle cells (PASMCs). Recent studies show that canonical transient receptor potential channel 6 (TRPC6) genes, which encode receptor-operated cation channels (ROCC) in PASMCs, play an important role in Ca2+ regulation and cell proliferation. The aim of the present study was to investigate the role of TRPC6 in monocrotaline (MCT)-induced pulmonary artery hypertension. Sprague-Dawley rats were randomly divided into normal control group and MCT group. In MCT group, pulmonary arterial hypertension was induced by a single intraperitoneal injection of MCT at a dose of 60 mg/kg. After 3 weeks, the right ventricular systolic pressure (RVSP) and the right ventricular mass index (RVMI) were measured. The lung sections were stained by HE and observed under light microscope. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blot were performed to detect the expression of TRPC6 in rat pulmonary arteries. The 1-oleoyl-2-acetyl-sn-glycerol (OAG)-induced contractile tension of pulmonary arteries were measured by vascular ring tension analysis and the intracellular Ca2+ concentration ([Ca2+](i))of PASMCs was monitored using Fluo3-AM assay. The results showed that RVSP and RVMI markedly elevated in MCT group (P<0.01) in comparison to CON group. The thickness of pulmonary vascular smooth muscles was increased and the inner diameter of pulmonary arteries was diminished in MCT group. Though there was no significant difference in the levels of mRNA and protein of TRPC6 between CON and MCT groups, the application of OAG, which can directly activate ROCC, induced greater contraction tension of pulmonary arteries (P<0.01) and more Ca2+ entries in PASMCs (P<0.05) in MCT group compared to those in control group. These results indicate that MCT induces pulmonary artery hypertension and thus remodeling of the right ventricle and pulmonary arteries in rats. The expression of mRNA and protein of TRPC6 is not potentiated by MCT, but the TRPC6/ROCC-mediated Ca2+ entry in PASMCs and vascular tone of pulmonary arteries are significantly increased with MCT treatment.


[The fluorescence characteristics of micelle inclusion of pefloxacin and its application].
A new highly sensitive fluorescence spectrophotometic method for the determination of pefloxacin (PEFX) has been developed based on micella enhancement. The fluorescence characteristic of micelle inclusion complex formed between PEFX and sodium dodecyl sulfate (SDS) was studied. Different variables and parameters affecting the fluorescence were studied and optimized. Experiments show that sodium dodecyl sulfate can enhance greatly the fluorescence signal for pefloxacin in pH 5 Britton Robinson(BR) buffer solution. The fluorimetric method allows the determination of 0.06-1.20 microg x mL(-1) of pefloxacin with SDS in aqueous solution with lambda ex = 278 nm and lambda em = 432 nm, respectively. The detection limit for PEFX is 0.06 microg x mL(-1), The recoveries are 98.5%-100.8% and the RSDs are 1.4%-2.3%. The proposed procedures could be applied successfully to the determination of the pefloxacin drugs in tablets and human plasma with good recovery. In this paper we determined pefloxacin in human plasma by synchronization-derivative fluorescence spectroscopic techniques with good analytical selectivity, high sensitivity, high capability of eliminating blank interference and improving the limit of detection.


[Aspects of the immunodepressive action of gentamycin and rifampicin].
The effects of rifampicin and gentamicin on the count of the antibody-forming cells (AFC), the titers of hemagglutinins, endogenous colony-formation and activity of the reticuloendothelial system (RES) were studied on uninbred albino mice. An attempt was made to correct the immunity defects induced by rifampicin. In addition to the inhibitory effect of the antibiotics on the primary immune response, i.e. the count of the AFC described earlier, suppression of hemagglutinin accumulation on the 4th day after immunization and inhibition of the absorption function of the RES after administration of rifampicin in a dose of 250 mg/kg were shown. Both the antibiotics induced stimulation of endogenic colony formation when administered for 10 days before the irradiation. It was only gentamicin that produced a stimulating effect after irradiation. The combined use of rifampicin with the immunostimulants prodigiozan, methyluracil or levamisole according to different schemes showed that the only effective combination was that of rifampicin with methyluracil (400 mg/kg) or levamisole (5 mg/kg).


Genetic conservation of Highlands J viruses.
We studied molecular evolution of the mosquito-borne alphavirus Highlands J (HJ) virus by sequencing PCR products generated from 19 strains isolated between 1952 and 1994. Sequences of 1200 nucleotides including portions of the E1 gene and the 3' untranslated region revealed a relatively slow evolutionary rate estimated at 0.9-1.6 x 10(-4) substitutions per nucleotide per year. Phylogenetic trees indicated that all HJ viruses descended from a common ancestor and suggested the presence of one dominant lineage in North America. However, two or more minor lineages probably circulated simultaneously for periods of years to a few decades. Strains isolated from a horse suffering encephalitis, and implicated in a recent turkey outbreak, were not phylogenetically distinct from strains isolated in other locations during the same time periods. Our findings are remarkably similar to those we obtained previously for another North American alphavirus, eastern equine encephalomyelitis virus, with which Highlands J shares primary mosquito and avian hosts, geographical distribution, and ecology. These results support the hypotheses that the duration of the transmission season affects arboviral evolutionary rates and vertebrate host mobility influences genetic diversity.


Impact of hurricanes katrina and rita on the anesthesiology workforce.
Hurricanes Katrina and Rita impacted a large portion of the medical community in Louisiana. We attempt to determine their impact on the anesthesiology workforce in Louisiana. In May 2006, a survey was mailed to 368 Louisiana anesthesiologists, collecting demographic data, retirement plans, impact of Hurricanes Katrina and Rita, position vacancies, practice conditions, and the general state of healthcare in their area. All 3 anesthesiology residency programs in the state were contacted regarding their recent graduates. The 2010 RAND survey of the anesthesiology workforce was reviewed with respect to findings relevant to the state and region. One hundred seventy surveys were returned, yielding a 46.2% response rate. Among the respondents, 13.9% intended to retire within 5 years and another 24% in 5 to 10 years. Since 2005, 63.9% had seen an increase in their daily caseload, 46.9% saw an increase in work hours, and 36.8% stated that their practices were trying to hire new anesthesiologists and were having difficulty filling these positions. Since 2005, the number of anesthesiology residents in Louisiana had declined by almost 50%, and the number of graduates remaining to practice in Louisiana had decreased by 43% from 7 to 4 annually. Our 2006 survey provided qualitative evidence for a shortage of anesthesiologists in the state of Louisiana after the natural disasters in 2005 that was likely to worsen as residency output plummeted, fewer residents stayed in the state, and projected retirement increased. The regional data from the RAND survey a year later confirmed the impressions from our survey, with an estimate of an anesthesiologist shortage as high as 39% of the workforce. State membership surveys may serve as accurate barometers in the wake of major environmental upheavals affecting regional anesthesiology workforce conditions.


Mechanisms of the penetration of blood-borne substances into the brain.
The blood-brain barrier (BBB) impedes the influx of intravascular compounds from the blood to the brain. Few blood-borne macromolecules are transferred into the brain because vesicular transcytosis in the endothelial cells is considerably limited and the tight junction is located between the endothelial cells. At the first line of the BBB, the endothelial glycocalyx which is a negatively charged, surface coat of proteoglycans, and adsorbed plasma proteins, contributes to the vasculoprotective effects of the vessels wall and are involved in maintaining vascular permeability. In the endothelial cytoplasm of cerebral capillaries, there is an asymmetrical array of metabolic enzymes such as alkaline phosphatase, acid phosphatase, 5'-nucleotidase, adenosine triphosphatase, and nucleoside diphosphatase and these enzymes contribute to inactivation of substrates. In addition, there are several types of influx or efflux transporters at the BBB, such as P-glycoprotein (P-gp), multidrug resistance associated protein, breast cancer resistance protein, organic anion transporters, organic cation transporters, organic cation transporter novel type transporters, and monocarboxylic acid transporters. P-gp, energy-dependent efflux transporter protein, is instrumental to the barrier function. Several findings recently reported indicate that endothelial P-gp contributes to efflux of undesirable substances such as beta-amyloid protein from the brain or periarterial interstitial fluid, while P-gp likely plays a crucial role in the genesis of multiple vascular abnormalities that accompany hypertension. In this review, influx and efflux mechanisms of drugs at the BBB are also reviewed and how medicines pass the BBB to reach the brain parenchyma is discussed.


Potent calcium phosphate nanoparticle surface coating for in vitro and in vivo siRNA delivery: a step toward multifunctional nanovectors.
The present study describes hybrid nanoparticles, built by alternate deposition of siRNA and modified polyethyleneimine (tyrosine-grafted PEI or tyrosine/galactose-grafted PEI) on calcium phosphate nanoparticles. These "easy to produce" nanoparticles (NPs) present an efficient gene silencing effect demonstrated in vitro in a luciferase expressing cell culture model and in vivo in a tumour xenograft mouse model. The luciferase gene silencing percentage reached up to 95% in vitro with biocompatible doses of siRNA. Interestingly, we show by SPECT imaging of radiolabeled particles that without modifying the size, stability and in vitro efficiency, the grafting of a sugar moiety on PEI can modify the in vivo biodistribution of the particles. The proof of concept that galactose-grafting on PEI could change biodistribution without changing the gene silencing efficiency makes them versatile tools for specific delivery of small interfering RNA. As they have been designed so far, biodistribution is mainly located in the liver and thus these innovative nanoparticles open a realistic and feasible strategy for siRNA delivery into the liver in vivo.


Pericardial fat is more abundant in patients with coronary atherosclerosis and even in the non-obese patients: evaluation with cardiac CT angiography.
Epicardial adipose tissue (EAT) may play an important role for developing an unfavorable cardiovascular risk profile. However, it has not been investigated if EAT is associated with coronary atherosclerosis in non-obese patients. We aimed to evaluate whether EAT is related to coronary atherosclerosis in non-obese patients. Among the consecutive patients who underwent coronary CT angiography(CCTA) with an intermediate pretest likelihood for having coronary artery disease, we excluded the patients whose body mass index (BMI) was over 30 kg/m(2) or whose CCTA image quality was not sufficient for the detection of coronary plaque. The remaining patients were divided into the normal and abnormal groups based on the presence of atherosclerotic plaques as seen on the CCTA images. The cardiovascular risk factors were matched between the two groups. Ultimately, 100 patients were included in the normal group and 100 patients were included in the abnormal group. The pericardial fat area was measured at the subaortic level of the heart on the axial CT images. The pericardial fat area was significantly larger in the abnormal group as compared to the normal group (18.1 +/- 10.2 vs. 14.6 +/- 8.7 cm(2),P = 0.019). Even though the overweight patients(25 </= BMI < 30) were excluded, the pericardial fat area was still significantly larger in the patients with coronary atherosclerotic plaque as compared to that of the patients without coronary atherosclerotic plaque (18.7 +/- 11.5 vs. 13.2 +/- 7.9 cm(2), P = 0.006). Pericardial fat was more abundant in the non-obese patients with coronary atherosclerosis as compared to that of the patients without coronary atherosclerosis,after controlling for the other cardiovascular risk factors.


[Neurologic disorders in chromosome abnormalities in children].
The authors describe neurological disorders in 134 children of different age. The results of clinical and paraclinical examinations, including computerized tomography of the brain are presented. The clinical symptomatology in this series is compared with the literature data.


Hepatocellular carcinoma--a case series of 104 patients.
The records of one hundred and four patients with confirmed hepatocellular carcinoma seen over a two year period at the National University Hospital were analysed to elucidate the clinical features of our local patients and to assess their response to various therapeutic modalities. Chinese males were over-represented with a peak frequency in the sixth to eighth decade of life. Seventy-five percent of the patients were HBsAg positive and at least 88% had evidence of previous Hepatitis B infection. Ninety-one percent were symptomatic at presentation with pain being the most common symptom. Hepatomegaly with features of cirrhosis were the main physical findings. Seventy percent of the patients presented within three months after the onset of symptoms. The majority of patients had stage II or III disease at diagnosis. Twenty percent of patients had normal alpha-fetoprotein levels. Chemotherapy did not appear to show a survival benefit. Curative surgical resection was feasible in about 10% of patients and it remains the only chance for long term survival. There is an urgent need to identify more effective drugs or other modalities to treat this common and rapidly fatal malignancy. Identification of high risk patients should prompt screening with both serum alpha-fetoprotein and ultrasonography of the liver.


Anthropometric characteristics of young Turkish male athletes.
Comparative reports on the anthropometric characteristics of athletes are certainly important in modern sports and have long been studied by sports scientists. Studies on Turkish athletes however, are limited. In the present study physical characteristics of athletes active in various sports (American football, basketball, volleyball and football) were observed and compared to each other and to those of non-athlete individuals. 153 volunteer male subjects participated in the study. All of the athletes were licensed members of teams in inter-university leagues. All subjects were given information about the objectives of the study and were advised of the manner with which the anthropometric measurements would be obtained. In addition to 17 anthropometric values, body mass index (BMI) and somatotype components were calculated and evaluated. Length, breadth, and girth values were evaluated by ANCOVA and height and weight were used as co-variate factors. The other variables were evaluated by metric and non-metric ANOVA. The results of the study indicate that basketball and volleyball players were characteristic with their longer lower limb length; American football players were with their wider biiliac breadth and higher girth values; and football players with their small structure. It was also observed that Turkish athletes have higher endomorphy and lower mesomorphy values when compared to athletes from other countries.


Plant-produced Recombinant Influenza A Vaccines Based on the M2e Peptide.
Influenza is a widely distributed infection that almost annually causes seasonal epidemics. The current egg-based platforms for influenza vaccine production are facing a number of challenges and are failing to satisfy the global demand in the case of pandemics due to the long production time. Recombinant vaccines are an alternative that can be quickly produced in high quantities in standard expression systems. Plants may become a promising biofactory for the large-scale production of recombinant proteins due to low cost, scalability, and safety. Plant-based expression systems have been used to produce recombinant vaccines against influenza based on two targets; the major surface antigen hemagglutinin and the transmembrane protein M2. Different forms of recombinant hemagglutinin were successfully expressed in plants, and some plantproduced vaccines based on hemagglutinin were successfully tested in clinical trials. However, these vaccines remain strain specific, while the highly conserved extracellular domain of the M2 protein (M2e) could be used for the development of a universal influenza vaccine. In this review, the state of the art in developing plant-produced influenza vaccines based on M2e is presented and placed in perspective. A number of strategies to produce M2e in an immunogenic form in plants have been reported, including its presentation on the surface of plant viruses or virus-like particles formed by capsid proteins, linkage to bacterial flagellin, and targeting to protein bodies. Some M2e-based vaccine candidates were produced at high levels (up to 1 mg/g of fresh plant tissue) and were shown to be capable of stimulating broad-range protective immunity.


Noise-Induced Sleep Disruption from Wind Turbines: Scientific Updates and Acoustical Standards.
Wind energy appears to place global environmental benefits against local human health, particularly sleep. The result is a significant challenge to wind-energy development for the achievement of large-scale alternative energy. Our purpose is to examine noise from wind turbines and its potential to disrupt sleep; to examine the human health literature addressing these concerns; and to provide insight into how developers and communities can employ these concepts to pursue wind energy without impacting human health. The latest and most rigorous research on noise from wind turbines points to healthy sleep, when turbines are sited reasonably. This includes audible noise, low-frequency noise and infrasound. Recent advances in acoustical standards provide practical methods to ensure compliance with these scientific findings. There now exist key data concerning wind-turbine noise, and its impact on sleep. Knowing that information, and how to deploy it with modern engineering standards should simultaneously facilitate wind development and protect human health.


A functional assay in yeast for the human estrogen receptor displays wild-type and variant estrogen receptor messenger RNAs present in breast carcinoma.
Human estrogen receptor (hER) variants or mutants with altered functional activity may be responsible for resistance to the antiestrogen tamoxifen in breast cancer. The method presented in this report is a screening method for functional activity of hER in yeast Saccharomyces cerevisiae. hER mRNA isolated from breast cancer tissue is subjected to reverse transcription-PCR, directly cloned into a yeast expression vector in vivo, and subsequently tested for functional activity in a simple yeast growth assay. This technique, functional analysis of separated alleles in yeast of the human estrogen receptor (hER-FASAY), gives a display of the prevalence and functional activity of all of the variant hER mRNAs among normal, wild-type receptors in a breast tumor sample. The hER-FASAY can discriminate among wild-type hER, constitutively active hER, and inactive hER. In contrast to standard immunohistochemistry, this assay gives insight into the functional activity of hER. The hER-FASAY was optimized and validated using breast cancer cell lines MCF-7 and T47D and seven breast cancer biopsies. Phenotypes detected with the hER-FASAY were validated by DNA sequencing. In both cell lines and tumor biopsies, hER variants are highly common and mainly caused by alternative RNA splicing, whereas point mutations and deletions occur only at low frequency.


Training and assessment of CXR/basic radiology interpretation skills: results from the 2005 CDIM Survey.
Despite published literature demonstrating deficiencies in chest radiograph (CXR)/basic radiology interpretation skills of 4th-year medical students, studies and subsequent curricula regarding the training needed to obtain these skills are lacking. Terms such as clinical exposure and radiology teaching have been used to describe the experience for these basic interpretive skills, but best practice methods of delivery, let alone common methods, have yet to be defined. The objective is to describe the current methods of teaching and assessing CXR/basic radiology interpretation skills across institutions on the 3rd-year internal medicine (IM) clerkship. In 2005, the Clerkship Directors in Internal Medicine (CDIM), an international organization representing U.S. and Canadian medical schools, surveyed its institutional members. Twelve questions on the survey dealt with X-ray interpretation. Eighty-eight of 109 members (81%) responded to the survey. Overall, 81% of respondents felt that CXR interpretation is an important clinical skill for medical students. Seventy-six percent indicated that instruction in these skills occurs on the IM clerkship. The most cited methods of instruction were lectures (56%) and teaching rounds (48%). Most schools spent on average of 2 to 4 hr during the IM clerkship on formal radiology instruction. Only 33% indicated that radiology interpretation skills are assessed during the clerkship. The most common assessment methods were written examination (19%) and OSCE (19%). Substantive data regarding attainment and assessment of CXR/basic radiology interpretation skills in the undergraduate curriculum are lacking. Our study provides preliminary descriptive data regarding CXR instruction and assessment on the 3rd-year IM clerkship.


Structural effect of avocado/soybean unsaponifiables on joint space loss in osteoarthritis of the hip.
To evaluate the structural effect of avocado/soybean unsaponifiables (ASU) in the treatment of patients with symptomatic osteoarthritis (OA) of the hip. Patients with regular painful primary OA of the hip (European League Against Rheumatism 1980 criteria) and a joint space still > or = 1 mm (Kellgren grade 1 to 3, assessed by an independent observer prior to inclusion) entered a prospective, multicenter, randomized, parallel group, double-blind, placebo-controlled trial of 2 years duration. Patients had at least a 6-month history of regular pain and an algofunctional index (AFI) > or = 4. The primary assessment criterion was a decrease of the joint space width (JSW) on plain anteroposterior radiographs of the pelvis performed in standing position, measured at the narrowest points by 2 independent readers, previously tested and selected and blinded to both the treatment and the time sequence. Secondary criteria were standard clinical outcome measurements (AFI, pain on a visual analog scale, consumption of nonsteroidal antiinflammatory drugs and patient's and investigator's global assessments). One hundred sixty-three patients were included: 102 men and 61 women (mean age 63.2 +/- 8.7 years). A total of 108 patients (72 men and 36 women; mean age 64 +/- 7.9 years) were radiologically evaluable at 23.7 +/- 2.6 months (ASU group; n = 55) and 23.7 +/- 3.2 months (placebo group; n = 53). Overall comparison of the evolution of JSW showed no difference between the ASU and placebo groups, from 2.35 +/- 0.93 to 1.87 +/- 1.10 mm and from 2.5 +/- 0.94 to 1.9 +/- 1.33 mm, respectively (intergroup P value at end point = 0.9). When patients were divided into 2 subgroups according to the median value of the baseline JSW (2.45 mm), the joint space loss in the most severely affected subgroup of patients (baseline JSW < or = median) was significantly greater in the placebo group than in the ASU group: from 1.69 +/- 0.58 to 0.84 +/- 0.77 mm (-0.86 +/- 0.62 mm) and from 1.66 +/- 0.42 to 1.22 +/- 0.7 mm (-0.43 +/- 0.51 mm), respectively (P < 0.01). The JSW decrease was identical, with no difference in ASU and placebo groups, in the less severely affected subgroup of patients (baseline JSW > median). Clinical parameters in the 2 groups did not differ significantly throughout the study. This pilot randomized, double-blind, placebo-controlled trial failed to demonstrate a structural effect of ASU in hip OA. However, in a post-hoc analysis, ASU significantly reduced the progression of joint space loss as compared with placebo in the subgroup of patients with advanced joint space narrowing. These results suggest that ASU could have a structural effect but require confirmation in a larger placebo-controlled study in hip OA.