Efficacy and efficiency of multivariate linear regression for rapid prediction of femoral strain fields during activity.
Multivariate Linear Regression-based (MLR) surrogate models were explored to reduce the computational cost of predicting femoral strains during normal activity in comparison with finite element analysis. The musculoskeletal model of one individual, the finite-element model of the right femur, and experimental force and motion data for normal walking, fast walking, stair ascent, stair descent, and rising from a chair were obtained from a previous study. Equivalent Von Mises strain was calculated for 1000 frames uniformly distributed across activities. MLR surrogate models were generated using training sets of 50, 100, 200 and 300 samples. The finite-element and MLR analyses were compared using linear regression. The Root Mean Square Error (RMSE) and the 95th percentile of the strain error distribution were used as indicators of average and peak error. The MLR model trained using 200 samples (RMSE < 108 µε; peak error < 228 µε) was used as a reference. The finite-element method required 66 s per frame on a standard desktop computer. The MLR model required 0.1 s per frame plus 1848 s of training time. RMSE ranged from 1.2% to 1.3% while peak error ranged from 2.2% to 3.6% of the maximum micro-strain (5020 µε). Performance within an activity was lower during early and late stance, with RMSE of 4.1% and peak error of 8.6% of the maximum computed micro-strain. These results show that MLR surrogate models may be used to rapidly and accurately estimate strain fields in long bones during daily physical activity.


Neurodegenerative diseases: neurotoxins as sufficient etiologic agents?
A dominant paradigm in neurological disease research is that the primary etiological factors for diseases such as Alzheimer's (AD), Parkinson's (PD), and amyotrophic lateral sclerosis (ALS) are genetic. Opposed to this perspective are the clear observations from epidemiology that purely genetic casual factors account for a relatively small fraction of all cases. Many who support a genetic etiology for neurological disease take the view that while the percentages may be relatively small, these numbers will rise in the future with the inevitable discoveries of additional genetic mutations. The follow up argument is that even if the last is not true, the events triggered by the aberrant genes identified so far will be shown to impact the same neuronal cell death pathways as those activated by environmental factors that trigger most sporadic disease cases. In this article we present a countervailing view that environmental neurotoxins may be the sole sufficient factor in at least three neurological disease clusters. For each, neurotoxins have been isolated and characterized that, at least in animal models, faithfully reproduce each disorder without the need for genetic co-factors. Based on these data, we will propose a set of principles that would enable any potential toxin to be evaluated as an etiological factor in a given neurodegenerative disease. Finally, we will attempt to put environmental toxins into the context of possible genetically-determined susceptibility.


Low-density granulocytes activate T cells and demonstrate a non-suppressive role in systemic lupus erythematosus.
The presence of proinflammatory low-density granulocytes (LDG) has been demonstrated in autoimmune and infectious diseases. Recently, regulatory neutrophilic polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) were identified in systemic lupus erythematosus (SLE). Because LDG and PMN-MDSC share a similar phenotype with contrasting functional effects, we explored these cells in a cohort of patients with SLE. LDG and normal-density granulocytes (NDG) were isolated from fresh blood of healthy donors (HD) and patients with SLE. Associations between LDG and clinical manifestations were analysed. Multicolor flow cytometry and confocal imaging were performed to immunophenotype the cells. The ability of LDG and NDG to suppress T cell function and induce cytokine production was quantified. LDG prevalence was elevated in SLE versus HD, associated with the interferon (IFN) 21-gene signature and disease activity. Also, the LDG-to-lymphocyte ratio associated better with SLE disease activity index than neutrophil-to-lymphocyte ratio. SLE LDG exhibited significantly heightened surface expression of various activation markers and also of lectin-like oxidised low-density lipoprotein receptor-1, previously described to be associated with PMN-MDSC. Supernatants from SLE LDG did not restrict HD CD4+ T cell proliferation in an arginase-dependent manner, suggesting LDG are not immunosuppressive. SLE LDG supernatants induced proinflammatory cytokine production (IFN gamma, tumour necrosis factor alpha and lymphotoxin alpha) from CD4+ T cells. Based on our results, SLE LDG display an activated phenotype, exert proinflammatory effects on T cells and do not exhibit MDSC function. These results support the concept that LDG represent a distinct proinflammatory subset in SLE with pathogenic potential, at least in part, through their ability to activate type 1 helper responses.


Meta-Analysis of BRCA1 Polymorphisms and Breast Cancer Susceptibility.
BRCA1 codes for a tumor suppressor protein involved in DNA repair. Based on the role of single nucleotide polymorphisms (SNPs) in the modification of gene expression and function and the existence of certain SNPs within 3-untranslated region of BRCA1 with the ability to change binding sites for mirRNAs, several association studies have been designed to explore the significance of SNPs within BRCA1 gene in conferring breast cancer (BC) risk. This study aims to assess the relationship between BRCA1 SNPs and BC using meta-analysis. To conduct a meta-analysis for retrieving case-control studies on the associations between the rs11655505, rs1799966, rs3737559, rs1799950, rs799917 and rs16941 BRCA1 polymorphisms and BC. The pooled odds ratios and its 95% confidence intervals were measured using fixed and random model to define the association between these polymorphisms and BC risk. No significant association was found for any of these polymorphisms and BC risk in the allelic, homozygote, dominant or recessive models. Overall, our study implies that the mentioned polymorphisms are not associated with BC risk. However, our study did not exclude the possible contribution of other SNPs within this gene in BC nor substantial contribution of multiple variants within this gene in conferring BC risk. Key words: BRCA1 - breast cancer - meta-analysis.


Predicting and controlling risks from human exposures to vibration and mechanical shock: flag waving and flag weaving.
At work or in leisure activities, many people are exposed to vibration or mechanical shocks associated with risks of injury or disease. This paper identifies information that can be used to decide whether there may be a risk from exposure to hand-transmitted vibration or whole-body vibration and shock, and suggests actions that can control the risks. The complex and time-varying nature of human exposures to vibration and shock, the complexity of the different disorders and uncertainty as to the mechanisms of injury and the factors influencing injury have prevented the definition of dose-response relationships well proven by scientific study. It is necessary to wave a flag indicating when there is a need to control risks from exposure to vibration and shock while scientific enquiry provides understanding needed to weave a better flag. It is concluded that quantifying exposure severity is often neither necessary nor sufficient to either identify risks or implement measures that control the risks. The identification of risks associated with exposure to vibration and mechanical shock cannot, and need not, rely solely on the quantification of exposure severity. Qualitative methods can provide a sufficient indication of the need for control measures, which should not be restricted to reducing standardised measures of exposure severity.


The syndemic effects of food insecurity, water insecurity, and HIV on depressive symptomatology among Kenyan women.
Depression is a leading cause of disability worldwide and a major contributor to the overall global burden of disease, especially for women of childbearing age. Social science scholarship has demonstrated significant relationships between mental health, food insecurity (FI), water insecurity (WI), and HIV. Little is known, however, about the temporal relationships between food and water insecurity or the mechanisms through which these multiple stressors may operate or interact to impact depression. We therefore used syndemic theory to explore the complex relationships between FI, WI, and HIV on depressive symptomatology among Kenyan women of mixed HIV status (n=183, NCT02979418). We sought to 1) understand the temporal relationships between time-variant risk factors for depression, i.e. FI and WI, and 2) assess how these factors potentially interacted with HIV to impact depressive symptomatology. We first assessed the bidirectional relationship between WI and FI using a cross-lagged three-wave, two-variable panel model. Next, we modeled depressive symptomatology at 21 months as a linear function of the potentially syndemic interaction between FI, WI, and HIV status, adjusting for household wealth. WI had a predominant predictive effect on FI (Bayesian posterior predictive p-value=0.13); there was no reverse causality for the influence of FI on WI. The interaction effect of FI, WI, and HIV was significantly associated with greater depressive symptomatology (β=0.06) at 21 months postpartum. These data suggest that water insecurity may be an important determinant of food insecurity. Further, the co-occurrence of FI, WI, and HIV increases the likelihood of maternal depressive symptomatology, i.e. there is a syndemic relationship. These findings suggest that the role of household WI in other adverse health outcomes beyond mental well-being should be examined, and that interventions to improve mental health will be more effective if they also consider concurrent resource insecurities, regardless of HIV status.


Absence of equid herpesvirus-1 reactivation and viremia in hospitalized critically ill horses.
Equid herpesvirus-1 (EHV-1) reactivation and shedding can occur in latently infected, asymptomatic animals. Risk factors for reactivation include stress and illness. The risk of asymptomatic shedding in hospitalized, critically ill horses with acute abdominal disease is unknown. This information is important to assess the need for additional biosecurity protocols to prevent spread of EHV-1 in hospitalized critically ill horses with acute abdominal disorders. To determine the frequency of reactivation and nasal shedding of EHV-1 in hospitalized critically ill horses. One hundred twenty-four client-owned horses admitted to the Veterinary Teaching Hospital with acute abdominal disorders were included in the study. Cross-sectional study examining the risk of reactivation of EHV-1 in horses admitted with acute, severe, gastrointestinal disease. Whole blood and nasal secretions were collected throughout hospitalization. In addition, mandibular lymph nodes were collected from 9 study horses and 26 other Michigan horses. All samples were tested for the presence of EHV-1 nucleic acid by real-time PCR assays targeting the glycoprotein B gene and the polymerase (ORF 30) gene. One hundred and twenty-four horses met the inclusion criteria. None of the samples were positive for EHV-1 DNA. These results suggest that nasal shedding and viremia of EHV-1 in hospitalized critically ill horses with acute abdominal disorder is extremely rare. Implementation of additional biosecurity protocols to limit aerosol spread of EHV-1 among horses with acute abdominal disease and other hospitalized horses is not necessary.


Primary eye care management.
Due to a financial recession in South Africa, the registered nurses (RNs) at an excimer laser center faced dismissal. In order to continue a career in ophthalmology, these nurses needed to create their own income. To this end, a primary eye care (PEC) clinic was established to provide examination and treatment(s) to the underprivileged community with the assistance of local ophthalmologists. The PEC clinic, which provides basic services for a nominal fee, has bridged the gap between excellent private eye care and inadequate government eye care. Since 1999, 791 patients have been examined and 515 surgical procedures have been performed.


Excellent Islet Yields after 18-h Porcine Pancreas Preservation by Ductal Injection, Pancreas Preservation with MK Solution, Bottle Purification, and Islet Purification Using Iodixanol with UW Solution and Iodixanol with MK Solution.
Successful islet isolation is the key to successful islet transplantation. Our group recently modified the islet isolation protocol to include pancreatic ductal injection of the preservation solution, pancreas storage in modified extracellular-type trehalose-containing Kyoto (MK) solution, and use of an iodixanol-based purification solution and bottle purification. In this study, we applied these methods to porcine islet isolation after 18-h pancreas preservation and compared two solutions with different compositions in bottle purification. Islet yield before purification was 651,661 ± 157,719 islet equivalents (IE) and 5576 ± 1538 IE/g pancreas weight. An IU solution was made by adding iodixanol to University of Wisconsin solution and an IK solution was made by adding iodixanol to MK solution. The efficacy of the two solutions for islet isolation was compared. There were no significant differences between the two purification methods with regard to islet yield, survival rate, purity, score, or stimulation index. These results indicate that our isolation protocol produces efficient islet yields from prolonged cold-stored pancreas and that IU and IK solutions are equally useful for islet purification.


Analysis of tumor characteristics and survival in liver transplant recipients with incidentally diagnosed hepatocellular carcinoma.
The use of orthotopic liver transplantation (OLTX) for the treatment of hepatocellular carcinoma (HCC) has generally become restricted to carefully selected cases of small oligocentric tumors. However, it is not uncommon to find previously undetected HCC within recipient cirrhotic livers at the time of hepatectomy. The impact of unsuspected HCC on patient outcomes remains unclear. A retrospective analysis of our institutional experience with adult primary OLTX was performed comparing recipients with incidental HCC (group 1), recipients with known or suspected HCC (group 2), and recipients confirmed by pathologic examination to be tumor free (group 3). Between 1984 and 2000, 27 patients in group 1, 12 patients in group 2, and 612 patients in group 3 underwent primary OLTX. Tumors were smaller (P = 0.0172) in group 1 than in group 2; however, the number of tumors and the histologic findings were similar in the groups. Incidence of bilobar involvement, vascular invasion, portal vein tumor thrombus, lymphatic involvement, and distant metastasis at the time of OLTX did not differ significantly between these groups. Four-year patient survival appeared to be lower in group 1 (70.0%) than in group 3 (79.0%) (P = 0.0546); 4-year patient survival was significantly worse in group 2 (31.0%) compared to group 3 (P = 0.0106). Thus, in our experience, incidentally diagnosed cases of HCC possess many of the same features of malignancy as preoperatively diagnosed HCC. Indeed, patient survival after OLTX appears to be adversely affected by the presence of incidental HCC.


Changes in cardiac pumping efficiency and intra-thoracic organ volume during negative pressure wound therapy of sternotomy wounds, assessment using magnetic resonance imaging.
Knowledge on the effects of negative pressure wound therapy (NPWT) on the intra-thoracic organs is limited. The present study was performed to investigate the effects of NPWT on the volume of the intra-thoracic organs, using magnetic resonance imaging (MRI), in a porcine sternotomy wound model. Six pigs underwent median sternotomy followed by NPWT at -75, -125 and -175 mmHg. Six pigs were not sternotomised. MR images covering the thorax and heart were acquired. The volumes of the thoracic cavity, lungs, wound fluid and heart were then determined. The volumes of the thoracic cavity and intra-thoracic organs increased after sternotomy and decreased upon NPWT application. The total heart volume variation, which is inversely related to cardiac pumping efficiency, was higher after sternotomy and decreased during NPWT. NPWT did not result in the evacuation of wound fluid from the bottom of the wound. NPWT largely closes and restores the thoracic cavity. Cardiac pumping efficiency returns to pre-sternotomy levels during NPWT. This may contribute to the clinical benefits of NPWT over open-chest care, including the stabilizing effects and the reduced need for mechanical ventilation.


Merkel cell carcinomas: expression of S-phase kinase-associated protein 2 (Skp2), p27, and proliferation markers.
Merkel cell carcinomas are rare and aggressive tumors about which the expression of cell cycle regulatory proteins are not well known. We evaluated the clinicopathologic features of Merkel cell carcinomas and examined the expression of the cell cycle regulatory markers p27 and S-phase kinase-associated protein 2 (Skp2) and the proliferation markers Ki-67 and DNA topoisomerase II alpha (topo II alpha) in a group of these tumors. Thirty-nine cases of Merkel cell carcinoma were studied, 19 from the Mayo Clinic, Rochester, MN, and 20 from the University of Torino, Torino, Italy. Although the University of Torino patients tended to be slightly older at time of surgery compared to the Mayo Clinic patients, no clinical, pathologic, or immunohistochemical feature was statistically significantly different between the two groups. Of the 39 patients, 20 were male and 19 were female. The age at surgery averaged 72 yr. Formalin-fixed paraffin-embedded archival tissues from the 39 Merkel cell carcinomas were analyzed by immunohistochemistry for p27, Skp2, Ki-67, and topo II alpha with the avidin-biotin peroxidase system. The distribution of immunoreactivity was analyzed by quantifying the percentage of positive nuclei, which was expressed as the labeling index. There was a statistically significant inverse relationship between p27 and Skp2 (p = 0.005). Most tumors with increased levels of Skp2 were associated with reduced p27, and tumors with high levels of p27 expression were associated with reduced levels of Skp2. These results suggest that Skp2 regulates p27 expression in Merkel cell carcinomas. Tumors showing increased Skp2 expression were not always correlated with increased proliferation as evaluated by Ki-67 and topo II alpha, suggesting that Skp2 may be involved in Merkel cell tumorigenesis, but that other factors may also influence cell proliferation in these tumors.


Ulnar Mammary syndrome and TBX3: expanding the phenotype.
We present a patient with features of Ulnar Mammary syndrome (UMS) consisting of bilateral ulnar defects, inverted nipples, short stature with associated growth hormone deficiency, and cryptorchidism. Our patient also had a hypoplastic anterior pituitary and an ectopic posterior pituitary gland, ventricular septal defect (VSD), and cardiac conduction defects consistent with Wolff-Parkinson-White (WPW) syndrome. Although TBX3 is known to be expressed in both the developing heart and the pituitary gland, conduction defects and anatomical pituitary abnormalities have not been previously described in UMS. This may, in part, be due to the fact that these features are not actively sought in individuals with UMS. Because these new findings have important clinical implications, we suggest that clinicians caring for individuals with UMS offer brain imaging, growth hormone testing, and cardiac arrhythmia screening. The diagnosis of UMS was confirmed on mutation analysis of TBX3. The mother of the propositus was also found to carry the same mutation, although she did not show the classical features of UMS. Therefore, our report also supports the variable expressivity of UMS within the same family.


Identification of whale species by thin-layer isoelectric focusing of sarcoplasmic proteins.
Thin-layer isoelectric focusing was applied to the identification of whale (Cetacea) species by using water-soluble sarcoplasmic proteins of skeletal muscles. Twenty-eight samples consisting of 4 species (10 samples) of baleen whales (Mysticeti) and 8 species (18 samples) of toothed whales (Odontoceti) were analyzed. Each sample (approximately 1 g) was electrophoresed with Ampholine PAGplate, pH 3.5-9.5. The electrophoretic profiles were species-specific on the 4 toothed whale species that did not have a marked intra-species difference, and all 4 baleen whale species. However, the profiles were not specific on the 4 other dolphin species, even though they were discriminable from the other 4 toothed whale species. Numerical values of pIs and relative peak heights were obtained by densitometric analysis of the isoelectro-focused protein bands. The bands were also species-specific for the 8 toothed whale species mentioned. The values may be applicable to species identification without the need for a standard sample, which may not be readily obtainable. Experiments on test samples of minke and sel whales showed that bloodletting with ice water made the densities of isoelectro-focused bands thinner, although species identification was still possible by using the inside part of muscles. Heat treatment at below 60 degrees C for 10 min caused little denaturation; at higher temperatures the protein bands were diminished in a temperature-dependent fashion. Therefore, the present isoelectric focusing analysis should be applicable to small samples of whale meat, excluding several species of dolphins.


[Nucleoside analogues resistance in the treatment of chronic hepatitis B virus infection].
Chronic hepatitis B virus (HBV) infection is usually treated by interferon alpha. However, a sustained response after stopping treatment is only obtained in 30% of patients. New therapeutic nucleoside analogs have been developed, i.e. lamivudine, famciclovir, adefovir, entecavir, clevudine. However, as in HIV infection, clearance of the original hepatitis B virus with emergence of distinct resistant mutants have been observed during or after treatment with most nucleoside analogs. In this review, the underlying mechanisms of resistance and the characterisation of HBV mutants are described to optimize the best therapeutic regimen. Treatment of chronic HBV infection, as most of other chronic viral infection, should be based on combination therapy with a special search for the appearance of HBV mutant resistant.


The Origin of the Legumes is a Complex Paleopolyploid Phylogenomic Tangle Closely Associated with the Cretaceous-Paleogene (K-Pg) Mass Extinction Event.
The consequences of the Cretaceous-Paleogene (K-Pg) boundary (KPB) mass extinction for the evolution of plant diversity remain poorly understood, even though evolutionary turnover of plant lineages at the KPB is central to understanding assembly of the Cenozoic biota. The apparent concentration of whole genome duplication (WGD) events around the KPB may have played a role in survival and subsequent diversification of plant lineages. To gain new insights into the origins of Cenozoic biodiversity, we examine the origin and early evolution of the globally diverse legume family (Leguminosae or Fabaceae). Legumes are ecologically (co-)dominant across many vegetation types, and the fossil record suggests that they rose to such prominence after the KPB in parallel with several well-studied animal clades including Placentalia and Neoaves. Furthermore, multiple WGD events are hypothesized to have occurred early in legume evolution. Using a recently inferred phylogenomic framework, we investigate the placement of WGDs during early legume evolution using gene tree reconciliation methods, gene count data and phylogenetic supernetwork reconstruction. Using 20 fossil calibrations we estimate a revised timeline of legume evolution based on 36 nuclear genes selected as informative and evolving in an approximately clock-like fashion. To establish the timing of WGDs we also date duplication nodes in gene trees. Results suggest either a pan-legume WGD event on the stem lineage of the family, or an allopolyploid event involving (some of) the earliest lineages within the crown group, with additional nested WGDs subtending subfamilies Papilionoideae and Detarioideae. Gene tree reconciliation methods that do not account for allopolyploidy may be misleading in inferring an earlier WGD event at the time of divergence of the two parental lineages of the polyploid, suggesting that the allopolyploid scenario is more likely. We show that the crown age of the legumes dates to the Maastrichtian or early Paleocene and that, apart from the Detarioideae WGD, paleopolyploidy occurred close to the KPB. We conclude that the early evolution of the legumes followed a complex history, in which multiple auto- and/or allopolyploidy events coincided with rapid diversification and in association with the mass extinction event at the KPB, ultimately underpinning the evolutionary success of the Leguminosae in the Cenozoic. [Allopolyploidy; Cretaceous-Paleogene (K-Pg) boundary; Fabaceae, Leguminosae; paleopolyploidy; phylogenomics; whole genome duplication events].


Exploring structural requirements of imaging agents against Aβ plaques in Alzheimer's disease: a QSAR approach.
Exploring molecular imaging agents against the beta amyloid (Aβ) plaques for an early detection of Alzheimer's disease (AD) is one of the emerging research areas in medicinal chemistry. In the present in-silico study, a congeneric series of 44 imaging agents, including 17 positron emission tomography (PET) and 27 single photon emission computed tomography (SPECT) imaging agents, was utilized to understand the structural features required for having essential binding affinity against Aβ plaques. Here, 2D-quantitative structure-activity relationship (2D-QSAR) and group-based QSAR (G-QSAR) models have been developed using genetic function approximation (GFA) and validated using various statistical metrics. Both the models showed satisfactory performance signifying the reliability and robustness of the developed QSAR models. The vital information gained from both the QSAR models will be useful in developing new PET and SPECT imaging agents and also in predicting their binding affinity against Aβ plaques. The results of this study would be important in view of the widespread clinical applicability of the SPECT imaging agents, especially in the developing countries. In this study, we have also designed some imaging agents based on the information provided by the models. Some of these designed compounds were predicted to be similar to or more active than the most active imaging agents present in the original dataset.


Determining the Instructional Effectiveness of Online Vaccine Education Modules: A Focus-Group Analysis.
This article was migrated. The article was marked as recommended. Vaccine education for pediatric and family medicine residents is inadequate. Implementation of evidence-based instructional design methods for medical education is understudied. We conducted four focus groups with residents who had completed a novel immunization curriculum to explore their satisfaction with design, content and impact on confidence. Data were analyzed using thematic content analysis. Overall satisfaction with the curriculum was high. Residents valued the interactive design and content, reported improvement in confidence in discussing vaccines with parents, and shared recommendations for future iterations of the modules. Technical challenges were reported with the learning management system. Medical education modules developed using best practices in instructional design were well-liked by trainees and future modules should be developed using these principles.


The prevention of postoperative deep vein thrombosis.
Numerous recent reports have appeared dealing with the prevention of postoperative deep vein thrombosis. Simple mechanical measures are inadequate, electrical stimulation has complications, but the motorised foot mover and pneumatic compression appear effective. Drugs such as coumadin, aspirin and dipyridamole are ineffective, but dextran and sodium pentosan polysulphate appear to have a place. However, if the efficacy and safety of low-dose subcutaneous heparin is statistically confirmed in a multicentre trial, it may lead to the elimination of the morbidity and mortality of postoperative thrombo-embolism.


Dietary myricetin intake is inversely associated with the prevalence of type 2 diabetes mellitus in a Chinese population.
Myricetin is a natural plant-derived inhibitor for α-glucosidase and α-amylase and possesses strong antioxidant activity. Myricetin is reported to be effective in treating many symptoms that are associated with type 2 diabetes mellitus (T2DM), therefore, we hypothesized that myricetin plays a preventive role in the development of T2DM. To test this hypothesis, we designed a cross-sectional population study, which included 24 138 subjects, with 1357 of them diagnosed with T2DM. A validated 100-item food frequency questionnaire was used to collect dietary information. Daily intakes of myricetin and nutrients were calculated, based on the Chinese food composition tables. Multiple logistic regression analysis models were used to analyze the relationship between the quartiles of myricetin intake and the prevalence of T2DM. We found that, in this Chinese population, the daily intake of myricetin was 120.5 ± 95.7 mg, with apple, peach, orange, pineapple, and sweet potato being the main food sources. Significant inverse trends were observed between intakes of myricetin and prevalence of T2DM in multivariable models (all p-trend <0.0001). The odds ratios (95% CI) for T2DM across the ascending quartiles of myricetin intake were: 1.00 (reference), 0.73 (0.61, 0.87), 0.61 (0.50, 0.75), and 0.51 (0.40, 0.64). This study showed that myricetin intake was inversely related to the prevalence of T2DM in this Chinese population, suggesting a protective effect of myricetin in the development of T2DM.


[Pathogenesis of hurricane keratitis].
Hurricane keratitis is an epithelial disorder of corneal transplants which occurs irrespectively of the type of local postoperative therapy used. The epithelial defects show a vortex-like arrangement resembling satellite photos of whirlwinds. Even before the development of punctate keratitis, fluorescein staining of the corneal surface reveals vortex-like figures corresponding to a varying thickness of the tear film in a vortex-like configuration. The irregularities in the tear film are due to an irregular profile of the corneal surface, the functional result of which is irregular astigmatism. The irregular surface profile in turn is caused by the approximation of incongruent wound edges and by sutures being too tightly drawn. Particularly when Healon is used, there is a tendency to draw the sutures tight, since a postoperative pressure increase with subsequent fistulation must be expected. Hurricane keratitis thus also appears to result indirectly from the use of Healon.


[Immunologic changes in active pulmonary tuberculosis treated with a fuzheng guben pill].
This paper reports the changes of immunity in treatment of active pulmonary tuberculosis with Fuzheng Guben Pill (FGP). The chemotherapy group consisted of 11 cases of active pulmonary tuberculosis and was cured by streptomycin (SM) and isonicotinylhydrazide (INH). The FGP group consisted of 14 cases of active pulmonary tuberculosis and was cured by SM and INH in combination with FGP. After 60 days of treatment, the subtype T-cell mediated immunity in the FGP group was recovered to normal level. (OKT3: 46.07 +/- 6.92 to 54.86 +/- 8.74; OKT4: 36.14 +/- 4.79 to 41.00 +/- 4.13, etc). The chemotherapy group had no obvious immunological change after medication. It was shown that FGP had an immunological modulation in active pulmonary tuberculosis patients.


Peripherally acting anti-CGRP monoclonal antibodies alter cortical gray matter thickness in migraine patients: A prospective cohort study.
Migraine is underpinned by central nervous system neuroplastic alterations thought to be caused by the repetitive peripheral afferent barrage the brain receives during the headache phase (cortical hyperexcitability). Calcitonin gene-related peptide monoclonal antibodies (anti-CGRP-mAbs) are highly effective migraine preventative treatments. Their ability to alter brain morphometry in treatment-responders vs. non-responders is not well understood. Our aim was to determine the effects of the anti-CGRP-mAb galcanezumab on cortical thickness after 3-month treatment of patients with high-frequency episodic or chronic migraine. High-resolution magnetic resonance imaging was performed pre- and post-treatment in 36 migraine patients. In this group, 19 patients were classified responders (≥50 % reduction in monthly migraine days) and 17 were considered non-responders (<50 % reduction in monthly migraine days). Following cross-sectional processing to analyze the baseline differences in cortical thickness, two-stage longitudinal processing and symmetrized percent change were conducted to investigate treatment-related brain changes. At baseline, no significant differences were found between the responders and non-responders. After 3-month treatment, decreased cortical thickness (compared to baseline) was observed in the responders in regions of the somatosensory cortex, anterior cingulate cortex, medial frontal cortex, superior frontal gyrus, and supramarginal gyrus. Non-responders demonstrated decreased cortical thickness in the left dorsomedial cortex and superior frontal gyrus. We interpret the cortical thinning seen in the responder group as suggesting that reduction in head pain could lead to changes in neural swelling and dendritic complexity and that such changes reflect the recovery process from maladaptive neural activity. This conclusion is further supported by our recent study showing that 3 months after treatment initiation, the incidence of premonitory symptoms and prodromes that are followed by headache decreases but not the incidence of the premonitory symptoms or prodromes themselves (that is, cortical thinning relates to reductions in the nociceptive signals in the responders). We speculate that a much longer recovery period is required to allow the brain to return to a more 'normal' functioning state whereby prodromes and premonitory symptoms no longer occur.


Influence of the mode of management of acute myocardial infarction on the inducibility of ventricular tachyarrhythmias with programmed ventricular stimulation after myocardial infarction.
Programmed ventricular stimulation (PVS) is a technique for screening patients at risk for ventricular tachycardia (VT) after myocardial infarction (MI), but the results might be difficult to interpret. To investigate the results of PVS after MI, according to date of completion. PVS results were interpreted according to the mode of MI management in 801 asymptomatic patients: 301 (group I) during the period 1982-1989, 315 (group II) during 1990-1999, and 185 (group III) during 2000-2010. The periods were chosen based on changes in MI management. Angiotensin-converting enzyme (ACE) inhibitors had been given since 1990; primary angioplasty was performed routinely since 2000. The PVS protocol was the same throughout the whole study period. Group III was older (61 +/- 11 years) than groups I (56 +/- 11) and II (58 +/- 11) (P < 0.002). Left ventricular ejection fraction (LVEF) was lower in group III (36.5 +/- 11%) than in groups I (44 +/- 15) and II (41 +/- 12) (P < 0.000). Monomorphic VT < 270 beats/min was induced as frequently in group III (28%) as in group II (22.5%) but more frequently than in group I (20%) (P < 0.03). Ventricular fibrillation and flutter (VF) was induced less frequently in group III (14%) than in groups I (28%) (P < 0.0004) and II (30%) (P < 0.0000). Low left ventricular ejection fraction (LVEF) and date of inclusion (before/after 2000) were predictors of VT or VF induction on multivariate analysis. Induction of non-specific arrhythmias (ventricular flutter and fibrillation) was less frequent than before 2000, despite the indication of PVS in patients with lower LVEF. This decrease could be due to the increased use of systematic primary angioplasty for MI since 2000.


Actin filaments in apical projections of the primate pigmented epithelial cell.
A highly-ordered array of filaments is found within the apical processes of retinal pigmented epithelial cells in monkeys and humans. These filaments, approximately 100 A in diameter and 250 A apart, line the cytoplasmic face of the plasma membrane, in parallel with the long axis of the apical processes. Since these filaments bind rabbit myosin subfrafment-1 to form arrowhead complexes, we conclude that they contain actin. Such membrane-bound actin filaments could have any of several different functions: they could stabilize the apical projections and by so doing play a cytoskeletal role, and/or they could take part in the phagocytosis of shed outer segment discs.


Differential activation of the middle-temporal complex to visual stimulation in migraineurs.
Differences between people with and without migraine on various measures of visual perception have been attributed to abnormal cortical processing due to the disease. The aim of the present study was to explore the dynamics of the basic interictal state with regard to the extrastriate, motion-responsive middle temporal area (MT-complex) with functional magnetic resonance imaging (fMRI) at 3 tesla using coherent/incoherent moving dot stimuli. Twenty-four migraine patients (12 with aura [MwA], 12 without aura [MwoA]) and 12 healthy subjects participated in the study. The individual cortical folding pattern was accounted for by using a cortical matching approach. In the inferior-posterior portion of the MT-complex, most likely representing MT, control subjects showed stronger bilateral activation compared to MwA and MwoA patients. Compared with healthy controls MwoA and MwA patients showed significantly stronger activation mainly at the left side in response to visual stimulation in the superior-anterior portion of the MT-complex, representing the medial-superior temporal area (MST). Our findings strengthen the hypothesis that hyperresponsiveness of the visual cortex in migraine goes beyond early visual areas, even in the interictal period.


Two distinct mechanisms for stimulation of oxygen-radical production by polymorphonuclear leucocytes.
Oxygen-radical production stimulated from rat polymorphonuclear leucocytes by either unopsonized latex particles (diameter = 1.01 microM) or chemotactic peptide (N-formyl-Met-Leu-Phe) was monitored by using luminol-dependent chemiluminescence. Azide inhibited by more than 80% the luminescence response induced by chemotactic peptide whether added before or after stimulation. However, the luminescence response to latex particles was progressively less susceptible to azide inhibition if the azide was added after the stimulus. Cytochalasin B, which was shown to abolish phagocytosis of the latex beads, also abolished the chemiluminescence response. However, the same cells showed a greatly enhanced response to chemotactic peptide. Cytochalasin B-treated cells secreted approx. 45% of total cellular myeloperoxidase in response to chemotactic peptide, but there was no detectable secretion in response to unopsonized latex particles. Microperoxidase equivalent to 20% of cellular peroxidase activity added to the cells before addition of the stimulus had no effect on the response to latex particles but increased approx. 2-fold the peak rate of chemiluminescence induced by chemotactic peptide. It was concluded that the unopsonized latex particles stimulated oxygen-radical production by the mechanism that involved endocytosis, whereas chemotactic peptide stimulated production by a mechanism that involved exocytosis of myeloperoxidase, the latter mechanism requiring an increase in intracellular free [Ca2+].


Metformin suppresses azoxymethane-induced colorectal aberrant crypt foci by activating AMP-activated protein kinase.
Metformin is widely used for the treatment of diabetes mellitus. Adenosine monophosphate-activated protein kinase (AMPK) is known to be activated by metformin and to inhibit the mammalian target of rapamycin (mTOR) pathway. The mTOR pathway plays an important role in the protein translational machinery and cell proliferation. We examined the effect of metformin on the suppression of colorectal carcinogenesis in chemical carcinogen-induced models. Seven-wk-old BALB/c mice were intraperitoneally (i.p.) injected with azoxymethane (AOM, 10 mg/kg) and then treated with or without metformin (250 mg/kg/d) for 6 wk (for the investigation of aberrant crypt foci [ACF] formation) or 32 wk (for polyp formation). We next investigated colonic epithelial proliferation using bromodeoxyuridine (BrdU) and the proliferating cell nuclear antigen (PCNA) labeling indices. Furthermore, to examine the indirect effect of metformin, the insulin resistance status and the serum lipid levels were assessed. Treatment with metformin significantly reduced ACF formation. The effect of metformin on colon polyp inhibition was relatively modest. No significant difference in body weight or glucose concentration was observed. The BrdU and PCNA indices decreased in mice treated with metformin. A Western blot analysis revealed that the phosphorylated mTOR, S6 kinase, and S6 protein levels in the colonic mucosa decreased significantly in mice treated with metformin. In conclusion, metformin suppresses colonic epithelial proliferation via the inhibition of the mTOR pathway through the activation of AMPK. As metformin is already used daily as an antidiabetic drug, it might be a safe and promising candidate for the chemoprevention of colorectal cancer.


Contrast-Enhanced Sonography with Biomimetic Lung Surfactant Nanodrops.
Nanodrops comprising a perfluorocarbon liquid core can be acoustically vaporized into echogenic microbubbles for ultrasound imaging. Packaging the microbubble in its condensed liquid state provides some advantages, including in situ activation of the acoustic signal, longer circulation persistence, and the advent of expanded diagnostic and therapeutic applications in pathologies which exhibit compromised vasculature. One obstacle to clinical translation is the inability of the limited surfactant present on the nanodrop to encapsulate the greatly expanded microbubble interface, resulting in ephemeral microbubbles with limited utility. In this study, we examine a biomimetic approach to stabilize an expanding gas surface by employing the lung surfactant replacement, beractant. Lung surfactant contains a suite of lipids and proteins that provide efficient shuttling of material from bilayer folds to the monolayer surface. We hypothesized that beractant would improve stability of acoustically vaporized microbubbles. To test this hypothesis, we characterized beractant surface dilation mechanics and revealed a novel biophysical phenomenon of rapid interfacial melting, spreading, and resolidification. We then harnessed this unique functionality to increase the stability and echogenicity of microbubbles produced after acoustic droplet vaporization for in vivo ultrasound imaging. Such biomimetic lung surfactant-stabilized nanodrops may be useful for applications in ultrasound imaging and therapy.


Tuning PAK Activity to Rescue Abnormal Myelin Permeability in HNPP.
Schwann cells in the peripheral nervous systems extend their membranes to wrap axons concentrically and form the insulating sheath, called myelin. The spaces between layers of myelin are sealed by myelin junctions. This tight insulation enables rapid conduction of electric impulses (action potentials) through axons. Demyelination (stripping off the insulating sheath) has been widely regarded as one of the most important mechanisms altering the action potential propagation in many neurological diseases. However, the effective nerve conduction is also thought to require a proper myelin seal through myelin junctions such as tight junctions and adherens junctions. In the present study, we have demonstrated the disruption of myelin junctions in a mouse model (Pmp22+/-) of hereditary neuropathy with liability to pressure palsies (HNPP) with heterozygous deletion of Pmp22 gene. We observed a robust increase of F-actin in Pmp22+/- nerve regions where myelin junctions were disrupted, leading to increased myelin permeability. These abnormalities were present long before segmental demyelination at the late phase of Pmp22+/- mice. Moreover, the increase of F-actin levels correlated with an enhanced activity of p21-activated kinase (PAK1), a molecule known to regulate actin polymerization. Pharmacological inhibition of PAK normalized levels of F-actin, and completely prevented the progression of the myelin junction disruption and nerve conduction failure in Pmp22+/- mice. Our findings explain how abnormal myelin permeability is caused in HNPP, leading to impaired action potential propagation in the absence of demyelination. We call it "functional demyelination", a novel mechanism upstream to the actual stripping of myelin that is relevant to many demyelinating diseases. This observation also provides a potential therapeutic approach for HNPP.


Molecular differential cross sections for x-ray coherent scattering in fat and polymethyl methacrylate.
Molecular differential cross sections for the coherent scattering of x-rays in polymethyl methacrylate (PMMA) and fat were determined from measured diffraction patterns in the interval chi = 0 to 6.4 nm-1 (chi = [sin theta/2)]/lambda; lambda being the incident wavelength having the units of nm and theta the scattering angle). All measurements were performed at a controlled temperature of 23 degrees C. The final results for PMMA show overall agreement when compared with the data existing in the literature. However, some discrepancies with the results reported by Kosanetzky et al in 1987 are found at the first three maxima. The data for filtered fat material are reported here for the first time. Finally, data sets of molecular form factors for fat and PMMA were compiled from the smoothed corrected experimental results by assuming these materials to be mono-molecular.


Predictors of HVOT performance in Parkinson's disease.
Evidence suggests that the Hooper Visual Organization Test (HVOT) has naming and executive components that vary in size depending on neurological diagnosis. The current study used a sample of individuals with Parkinson's disease (PD) to demonstrate for the first time that an executive measure can be the best predictor of HVOT performance. Forty-eight nondemented and nondepressed individuals with idiopathic PD completed the HVOT and other measures of visuoperception, executive function, and visual confrontation naming. Despite average performance on all neuropsychological measures, an executive measure, time to complete Trail-Making Test Part B minus time to complete Part A, was clearly the best predictor of HVOT performance in a standard regression. The pattern of neurocognitive predictors is unlike that reported in healthy individuals and other patient samples. This finding suggests that the presence of a neuropathological process can alter neurocognitive correlates even when performance is intact, and supports the contention that executive function is paramount in the cognitive profile associated with PD.


Study of an enzyme immunoassay kit for carcinoembryonic antigen.
We evaluated a commercial enzyme immunoassay kit for carcinoembryonic antigen (CEA) based on a non-competitive "sandwich principle" method (Abbott Laboratories). The serum sample is treated with an acid buffer and the supernate is incubated with an anti-CEA coated polystyrene bead. After washing, the bead is incubated with an anti-CEA/peroxidase conjugate. After a second washing, the activity of the enzyme bound to the solid phase is assayed after addition of a chromogenic substrate. This activity is proportional to the concentration of CEA in the serum sample. The characteristics of the assay are: (a) good sensitivity (around 0.25 microgram/L) and (b) satisfactory reproducibility (CV < 11% within assay). There is little cross reactivity between CEA and molecules such as nonspecific cross-reacting antigens that are known for their high potential of cross reactivity. No nonspecific interference was encountered with anti-globulin factors. We compared results with this enzyme immunoassay kit with those by a radioimmunoassay provided by the Commissariat à l'Energie Atomique. The correlation (r) was 0.95 (p < 0.001). The distribution of CEA values obtained for 1020 normal subjects is given. We conclude that the kit provides a simple and reliable procedure.


X-ray free-electron laser studies reveal correlated motion during isopenicillin N synthase catalysis.
Isopenicillin N synthase (IPNS) catalyzes the unique reaction of l-δ-(α-aminoadipoyl)-l-cysteinyl-d-valine (ACV) with dioxygen giving isopenicillin N (IPN), the precursor of all natural penicillins and cephalosporins. X-ray free-electron laser studies including time-resolved crystallography and emission spectroscopy reveal how reaction of IPNS:Fe(II):ACV with dioxygen to yield an Fe(III) superoxide causes differences in active site volume and unexpected conformational changes that propagate to structurally remote regions. Combined with solution studies, the results reveal the importance of protein dynamics in regulating intermediate conformations during conversion of ACV to IPN. The results have implications for catalysis by multiple IPNS-related oxygenases, including those involved in the human hypoxic response, and highlight the power of serial femtosecond crystallography to provide insight into long-range enzyme dynamics during reactions presently impossible for nonprotein catalysts.


A translatable predictor of human radiation exposure.
Terrorism using radiological dirty bombs or improvised nuclear devices is recognized as a major threat to both public health and national security. In the event of a radiological or nuclear disaster, rapid and accurate biodosimetry of thousands of potentially affected individuals will be essential for effective medical management to occur. Currently, health care providers lack an accurate, high-throughput biodosimetric assay which is suitable for the triage of large numbers of radiation injury victims. Here, we describe the development of a biodosimetric assay based on the analysis of irradiated mice, ex vivo-irradiated human peripheral blood (PB) and humans treated with total body irradiation (TBI). Interestingly, a gene expression profile developed via analysis of murine PB radiation response alone was inaccurate in predicting human radiation injury. In contrast, generation of a gene expression profile which incorporated data from ex vivo irradiated human PB and human TBI patients yielded an 18-gene radiation classifier which was highly accurate at predicting human radiation status and discriminating medically relevant radiation dose levels in human samples. Although the patient population was relatively small, the accuracy of this classifier in discriminating radiation dose levels in human TBI patients was not substantially confounded by gender, diagnosis or prior exposure to chemotherapy. We have further incorporated genes from this human radiation signature into a rapid and high-throughput chemical ligation-dependent probe amplification assay (CLPA) which was able to discriminate radiation dose levels in a pilot study of ex vivo irradiated human blood and samples from human TBI patients. Our results illustrate the potential for translation of a human genetic signature for the diagnosis of human radiation exposure and suggest the basis for further testing of CLPA as a candidate biodosimetric assay.


Characterization and functional study of a cluster of four highly conserved orphan adhesion-GPCR in mouse.
Adhesion G protein-coupled receptors (aGPCR) constitute a structurally and functionally diverse class of seven-transmembrane receptor proteins. Although for some of the members important roles in immunology, neurology, as well as developmental biology have been suggested, most receptors have been poorly characterized. We have studied evolution, expression, and function of an entire receptor group containing four uncharacterized aGPCR: Gpr110, Gpr111, Gpr115, and Gpr116. We show that the genomic loci of these four receptors are clustered tightly together in mouse and human genomes and that this cluster likely derives from a single common ancestor gene. Using transcriptional profiling on wild-type and knockout/LacZ reporter knockin mice strains, we have obtained detailed expression maps that show ubiquitous expression of Gpr116, co-expression of Gpr111 and Gpr115 in developing skin, and expression of Gpr110 in adult kidney. Loss of Gpr110, Gpr111, or Gpr115 function did not result in detectable defects, indicating that genes of this aGPCR group might function redundantly. The aGPCR cluster Gpr110, Gpr111, Gpr115, and Gpr116 developed from one common ancestor in vertebrates. Expression suggests a role in epithelia, and one can speculate about a possible redundant function of GPR111 and GPR115.


Diversity of ATM gene variants: a population-based genome data analysis for precision medicine.
Ataxia-telangiectasia (AT) is a rare autosomal recessive disorder that causes deficiency or dysfunction of the ataxia-telangiectasia mutated (ATM) protein. Not only AT patients, but also certain ATM heterozygous mutation carriers show a significantly reduced life expectancy due to cancer and ischemic heart disease; in particular, female carriers having particular alleles have an increased risk of breast cancer. The frequency of such risk heterozygotes at a population level remains to be fully determined, and evidence-based preventive medical guidelines have not yet been established. Using the 3.5KJPNv2 allele frequency panel of Japanese Multi Omics Reference Panel v201902, which shows single-nucleotide variant (SNV) and insertion/deletion (INDEL) allele frequencies from 3552 Japanese healthy individuals, we investigated the diversity of ATM gene variants. We detected 2845 (2370 SNV and 475 INDEL) variants in the ATM gene, including 1338 (1160 SNV and 178 INDEL) novel variants. Also, we found a stop-gained SNV (NC_000008.11:g.108115650G > A (p.Trp266*)) and a disruptive-inframe-deletion (NC_000008.11:g. 108181014AAGAAAAGTATGGATGATCAAG/A (p.Ala1945_Phe1952delinsVal) and two frameshift INDELs (NC_000008.11:g.108119714CAA/C (p.Glu376fs) and NC_000008.11:g.108203577CTTATA/C (p.Ile2629fs)), which would be novel variants predicted to lead to loss of ATM functionality. The combination of population-based biobanking and human genomics provided a novel insight of diversity of ATM gene variants at a population level. For the advancement of precision medicine, such approach will be useful to predict novel pathogenic/likely pathogenic variants in the ATM gene and to establish preventive medical guidelines for certain ATM heterozygotes pertaining to their risk of particular diseases.


The Portuguese Severe Asthma Registry: Development, Features, and Data Sharing Policies.
The Portuguese Severe Asthma Registry (Registo de Asma Grave Portugal, RAG) was developed by an open collaborative network of asthma specialists. RAG collects data from adults and pediatric severe asthma patients that despite treatment optimization and adequate management of comorbidities require step 4/5 treatment according to GINA recommendations. In this paper, we describe the development and implementation of RAG, its features, and data sharing policies. The contents and structure of RAG were defined in a multistep consensus process. A pilot version was pretested and iteratively improved. The selection of data elements for RAG considered other severe asthma registries, aiming at characterizing the patient's clinical status whilst avoiding overloading the standard workflow of the clinical appointment. Features of RAG include automatic assessment of eligibility, easy data input, and exportable data in natural language that can be pasted directly in patients' electronic health record and security features to enable data sharing (among researchers and with other international databases) without compromising patients' confidentiality. RAG is a national web-based disease registry of severe asthma patients, available at asmagrave.pt. It allows prospective clinical data collection, promotes standardized care and collaborative clinical research, and may contribute to inform evidence-based healthcare policies for severe asthma.


Occurrence of hand-foot-and-mouth disease pathogens in domestic sewage and secondary effluent in Xi'an, China.
Hand, foot and mouth disease (HFMD), caused by a group of enteric viruses such as Enterovirus 71 (EV71), Coxsackievirus A16 (CVA16) and Coxsackievirus A10 (CVA10), is heavily epidemic in East Asia. This research focused on investigating the occurrence of HFMD pathogens in domestic sewage and secondary effluent before disinfection in a wastewater treatment plant (WWTP) in Xi'an, the largest megacity in northwest China. In order to simultaneously detect all three HFMD pathogens, a semi-nested RT-PCR assay was constructed with a newly designed primer set targeting conservative gene regions from the 5' untranslated region (UTR) to VP2. As a result, 86% of raw sewage samples and 29% of the secondary effluent samples were positive for the HFMD viral gene, indicating that HFMD pathogens were highly prevalent in domestic wastewater and that they could also persist, even with lower probability, in the secondary effluent before disinfection. Of the three HFMD pathogens, CVA10 was positive in 48% of the total samples, while the occurrences of CVA16 and EV71 were 12% and 2%, respectively. It could thus be stated that CVA10 is the main HFMD pathogen prevailing in the study area, at least during the investigation period. High genetic diversity in the conservative gene region among the same serotype of the HFMD pathogen was identified by phylogenetic analysis, implying that this HFMD pathogen replicates frequently among the population excreting the domestic sewage.


Association between prenatal exposure to traffic-related air pollution and preterm birth in the PELAGIE mother-child cohort, Brittany, France. Does the urban-rural context matter?
Evidence has accumulated that exposure to ambient air pollution during pregnancy may influence preterm birth (PTB) in urban settings. Conversely, this relation has barely been investigated in rural areas where individual characteristics (demographic, socioeconomic, and psychosocial factors) and environmental co-exposures may differ. We examined the association between prenatal exposure to traffic-related air pollution and PTB among pregnant women from the PELAGIE mother-child cohort (Brittany, France, 2002-2006) living in urban (n=1550) and rural (n=959) settings. Women's residences were classified as either urban or rural according to the French census bureau rural-urban definitions. Nitrogen dioxide (NO2) concentrations at home addresses were estimated from adjusted land-use regression models as a marker of traffic-related pollution. Associations between NO2 concentrations and PTB were assessed with logistic regression models. Prevalence of PTB was similar among women living in urban (3.2%) and in rural (3.5%) settings. More positive socioeconomic characteristics and health behaviors but more single-parent families were observed among urban women. NO2 exposure averaged 20.8±6.6 µg m(-3) for women residing in urban areas and 18.8±5.6 µg m(-3) for their rural counterparts. A statistically significant increased risk of PTB was observed among women exposed to NO2 concentrations ≥16.4 µg m(-3) and residing in urban areas but not among their rural counterparts. The results of this study, conducted in a region with interspersed urban-rural areas, are in line with previous findings suggesting an increased risk of PTB associated with higher NO2 concentrations for women living in urban areas. The absence of association among their rural counterparts for whom exposure levels were similar suggests that environmental mixtures and psychosocial inequalities might play a role in this heterogeneity.


Forest cover reduces thermally suitable habitats and affects responses to a warmer climate predicted in a high-elevation lizard.
Warmer climates have affected animal distribution ranges, but how they may interact with vegetation patterns to affect habitat use, an important consideration for future wildlife management, has received little attention. Here, we use a biophysical model to investigate the potential thermal impact of vegetation pattern on the habitat quality of a high-elevation grassland lizard, Takydromus hsuehshanensis, and to predict the thermal suitability of vegetation for this species in a future warmer climate (assuming 3 °C air temperature increase). We assess the thermal quality of vegetation types in our study area (Taroko National Park in areas >1,800 m) using three ecologically relevant estimates of reptiles: body temperature (T b), maximum active time, and maximum digestive time. The results show that increasing forest canopy gradually cools the microclimates, hence decreasing these estimates. In the current landscape, sunny mountain-top grasslands are predicted to serve as high quality thermal habitat, whereas the dense forests that are dominant as a result of forest protection are too cold to provide suitable habitat. In simulated warmer climates, the thermal quality of dense forests increases slightly but remains inferior to that of grasslands. We note that the impact of warmer climates on this reptile will be greatly affected by future vegetation patterns, and we suggest that the current trend of upslope forest movement found in many other mountain systems could cause disadvantages to some heliothermic lizard species.


[Food ingestion in ruminants: modalities and associated phenomena].
This paper synthesizes the literature on modalities of food intake in ruminants and their main associated phenomena. Firstly, circadian distribution of feeding and ruminating activities has been examined. Ruminants spend a large part of their time chewing. Their meals have been described in detail; changes in rates of intake, time spent eating, the effect of restricting the amount fed or the period of feed accessibility have been discussed. When food is distributed, the animals have a "long" meal. These meals have been analysed in relation to the type of animal and the feed offered. The other meals ("small" meals) have been briefly described. The paper next examines the phenomena associated with meals, or induced by them, and implied in the control of food intake. Forestomach motricity varies according to ruminant feeding behavior and plays a basic role in digesta transit. Rumen content varies with the meal and its chemical composition due to the arrival in the rumen of food, water and saliva. Rumination may require 600 to 650 min/day and is important in the comminution and sorting of rumen particles. The digestive phenomena associated with meals are related to control of intake. The influence of rumen fill has been thoroughly discussed. Finally, main humoral changes due to intake have been reviewed. The influence of volatile fatty acids (VFA) and metabolites has been discussed as well as the role of glucose, amino acids and fatty acids. Among the hormones, insulin and glucagon seem to play an important role in controlling food intake. The amounts of gastrointestinal hormones increase during intake and may also play an important part. Despite a net improvement in the knowledge of phenomena related to intake, much still remains to be done in setting up models to describe these phenomena in relation to feeding activities and to aid in understanding the mechanisms controlling feed intake in ruminants.


Applications of Receptor- and Ligand-based Models in Inverse Docking Experiments: Recognition of Dihydrofolate Reductase Using 7,8-Dialkyl- 1,3-Diaminopyrrolo[3,2-f]Quinazolines.
Inverse (or reverse) docking approach which involves docking of a ligand against a set of protein structures to predict possible protein target(s), possess limitations, including inefficient empirical scoring schemes and similarities in protein active site shape and physico-chemical properties. To overcome this limitation, we combined receptor- and ligand-based methods to predict probable protein targets. We showed that the experimental protein target along with possible offtargets can be effectively retrieved if the docking energy of the reference molecule and probe molecules based scaled energy profiles were combined and clustered together. The present method was validated using 7,8-dialkyl-1,3-diaminopyrrolo[3,2-f]quinazolines that inhibit Candida albicans dihydrofolate reductase (DHFR) in vitro.


Efficacy and Biocompatibility of Neutral Icodextrin Peritoneal Dialysis Fluid.
Neutral icodextrin peritoneal dialysis (PD) fluid (n-ICO) has become available for use in Japan. However, removal of water and solutes remains to be elucidated in detail. The present study was designed to determine removal of water, electrolytes, and small, middle, and large molecules in a period of 16 hours. In addition, biocompatibility with respect to peritoneal mesothelial cells was determined.Three stable patients undergoing PD at Tohoku University Hospital were administered n-ICO. Water removal was monitored every 2 hours. Sodium, urea nitrogen [molecular weight (MW): 28 Da], uric acid (MW: 168 Da), β2-microglobulin [β2M (MW: 11,800 Da)], α1-microglobulin [α1M (MW: 33,000 Da)], albumin (MW: 66,000 Da), and immunoglobulin G (MW: 160,000 Da) were measured in plasma and dialysate.Primary human peritoneal mesothelial cells were collected from 6 patients. Equal numbers of cells were seeded into 96-well culture plates and cultured for 12 hours. Culture medium was then replaced with dialysate, and 24-hour cell proliferation was determined by WST-1 assay.Water removal was sustained for 16 hours with n-ICO. The Na concentration in effluent did not change over that time. Small molecules such as urea nitrogen and uric acid were rapidly removed. Thus, their dialysate-to-plasma concentration ratio (D/P) approached 1.0 (equilibrium) in 2 - 4 hours. The D/P values for the larger molecules β2M and α1M were 0.4 and less than 0.1 respectively at 16 hours. However, larger molecules were removed in a time-dependent manner.Cell proliferation with n-ICO PD fluid was not different from that with lactate-buffered glucose PD fluid, but was increased from that with acidic icodextrin PD fluid (a-ICO).Water and solute removal with the new n-ICO is not much different from that with a-ICO. However, biocompatibility as reflected by cell proliferation was superior under n-ICO than under a-ICO and equal to proliferation under glucose PD fluid.


The mechanism of action of antidepressants revised.
The discovery of the clinical efficacy of imipramine and of the MAO-inhibitor iproniazid intensively stimulated biochemical-pharmacological research on the mechanism of action of antidepressants. Due to these investigations, until recently an enhanced activity of the central noradrenergic and/or serotonergic transmitter system was considered essential for the clinical antidepressive action. Such enhancement could be achieved either presynaptically by blocking alpha 2-adrenergic receptors, or in the synaptic cleft by inhibiting the transmitter reuptake or the main metabolic enzyme, MAO. The common final result, especially of chronic treatment, was the down-regulation of postsynaptic beta-receptors, modulated by interaction with the serotonergic system, neuropeptides, and hormones. The delay of clinical response corresponded better with such receptor alterations. However, the introduction of new, more selective antidepressants led to new reflections upon the mechanism of action. On the level of transmitters, alpha 1-upregulation, increased activity of the dopaminergic system, an alteration in the balance between the different transmitter systems, are reported and seem to be important. Most promising are recent investigations of the second messenger systems, the adenylate cyclase system and the phosphatidylinositol system. Both systems are modulated by antidepressant drugs including lithium and carbamazepine. These second messengers, in turn, modulate the phosphorylation status of neuronal proteins via protein kinase, which may lead to elevations of the above mentioned receptors and again their transduction systems.


Workers' compensation status: does it affect orthopaedic surgery outcomes? A meta-analysis.
Previous reviews have demonstrated that patient outcomes following orthopaedic surgery are strongly influenced by the presence of Workers' Compensation. However, the variability in the reviews' methodology may have inflated the estimated strength of this association. The main objective of this meta-analysis is to evaluate the influence of Workers' Compensation on the outcomes of orthopaedic surgical procedures. We conducted a systematic search of the literature published in this area from 1992-2012, with no language restrictions. The following databases were used MEDLINE (Ovid), Embase (Ovid), CINAHL, Google Scholar, LILACS and Pubmed. We also hand-searched the reference sections of all selected papers. We included all prospective studies evaluating the effect of compensation status on outcomes in adult patients who had undergone surgery due to orthopaedic conditions or diseases. Outcomes of interest included disease specific, region specific and/or overall quality of life scales/questionnaires and surgeons' personal judgment of the results. We used an assessment tool to appraise the quality of all included studies. We used Review Manager to create forest plots to summarize study data and funnel plots for the assessment of publication bias. Twenty studies met our eligibility criteria. The overall risk ratio for experiencing an unsatisfactory result after orthopaedic surgery for patients with compensation compared to non-compensated patients is 2.08 (95% CI 1.54-2.82). A similar association was shown for continuous data extracted from the studies using assessment scales or questionnaires (Standard Mean Difference = -0.70 95% CI -0.97- -0.43). Among patients who undergo orthopaedic surgical procedures, those receiving Workers' Compensation experience a two-fold greater risk of a negative outcome. Our findings show a considerably lower estimate of risk compared to previous reviews that include retrospective data. Further research is warranted to determine the etiological explanation for the influence of compensation status on patient outcomes. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42012002121.


Cut and sew: benzofuran-ring-opening enabled cyclopentenone ring formation.
A facile approach to the fully substituted cyclopentenones involving an unprecedented benzofuran-ring-opening is described. The cleavage of a benzofuran endocyclic C2-O bond proceeded smoothly in the absence of any transition metal catalyst or highly reactive organometallic reagent. Such benzofuran-ring-opening is delicately incorporated into an acid-catalyzed cascade process, orchestrating a novel synthetic strategy for complex cyclopentenones with excellent yields and diastereoselectivities.


Comorbid major depressive disorder in cognitive-behavior group treatment for social anxiety disorder: An examination of processes of symptom change.
Individuals with social anxiety disorder (SAD) typically have elevated depressive symptoms and approximately 50% also meet criteria for major depressive disorder (MDD; Beesdo et al., 2007). In the present study, we examined the relationship between social anxiety and depressive symptoms during cognitive-behavior group treatment (CBGT) for SAD. Specifically, we compared individuals with SAD and comorbid MDD and individuals with SAD without MDD to examine the role of MDD as a moderator of social anxiety-depression relationship. Participants were 90 individuals seeking treatment for SAD (36% were diagnosed with MDD), who completed self-report measures of social anxiety and depression every 2 weeks during CBGT. Lower level mediational modeling indicated that for individuals without MDD, a reciprocal relationship was observed in which changes in both social anxiety and depressive symptoms mediated changes in each other. However, changes in social anxiety explained all subsequent changes in depression, whereas changes in depression explained 11.26% of subsequent changes in social anxiety. For individuals with both SAD and MDD, neither social anxiety nor depression significantly mediated changes in each other. Our findings suggest that different processes of change occur for individuals with and without MDD and clinical implications of these findings are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Phospholipid of the rat glomerular basement membrane in experimental nephrosis.
Phospholipids were found to be a constant component of rat glomerular basement-membrane preparations. The concentration fell during preparation of basement membrane by sonication of whole glomeruli, but then remained constant despite continued sonication. The proportions of the individual phospholipids were different from those of whole renal tissue or of isolated glomeruli. The basement-membrane preparations had no (Na(+)+K(+))-activated adenosine triphosphatase activity, an enzyme that is bound to plasma membranes. The concentration of lipid P was decreased on exposure in vivo or in vitro to antiserum against basement membrane; 7 days after injection of antiserum there was a change in the phospholipid composition, with a relative increase in phosphatidylcholine and a decrease in sphingomyelin content. The metabolic turnover rate of the lipid P remaining in the membrane was normal, as determined by (32)P incorporation. The loss of phospholipid was associated with decreases in the relative concentrations of hydroxyproline, hydroxylysine and glycine, and relative increases in proline, lysine, serine, threonine and valine. Administration of aminonucleoside and daunomycin produced proteinuria but did not cause a decrease in lipid P. Anticollagen and anti-lymphocyte sera that attached to the basement membrane but failed to produce proteinuria, also failed to affect the phospholipid content.


Some physical and radiobiological properties of immunologically reactive mouse spleen cells.
Three classes of immunologically reactive cells, differing only slightly in size from each other, are required for the production of hemolysin-forming cells in culture. The three classes of cells can be detected in the normal mouse spleen by the combined use of rosette formation, velocity sedimentation, and irradiation. One class of cells (peak sedimentation velocity, 3.2 mm per hr) forms rosettes. The capacity of these cells to participate in immune responses to foreign erythrocytes is inhibited by relatively low doses of irradiation. These cells may be the immediate precursors of hemolysin-forming cells. A second class of cells (peak sedimentation velocity, 3.6 mm per hr) facilitates the production of hemolysin-forming cells by small numbers of normal spleen cells. Their facilitative activity is resistant to a relatively large dose of radiation. They do not form rosettes. The requirement of a third class of cells was deduced from the results of mixing experiments. Neither rosette-forming cells nor spleen cells largely depleted of rosette-forming cells could give rise to hemolysin-forming cells when cultured either alone or in the presence of large numbers of heavily irradiated cells. However, when rosette-forming cells, cells depleted of rosette-forming cells, and heavily irradiated cells were mixed together, hemolysin-forming cells were produced. The peak responses were found in fractions sedimenting at 4 mm per hr. Thus, it is suggested that these fractions contain a third class of cells. This class of cells does not form rosettes, but its function is inhibited by relatively low doses of radiation.


Mammary Gland Pathology Subsequent to Acute Infection with Strong versus Weak Biofilm Forming Staphylococcus aureus Bovine Mastitis Isolates: A Pilot Study Using Non-Invasive Mouse Mastitis Model.
Biofilm formation by Staphylococcus aureus is an important virulence attribute because of its potential to induce persistent antibiotic resistance, retard phagocytosis and either attenuate or promote inflammation, depending upon the disease syndrome, in vivo. This study was undertaken to evaluate the potential significance of strength of biofilm formation by clinical bovine mastitis-associated S. aureus in mammary tissue damage by using a mouse mastitis model. Two S. aureus strains of the same capsular phenotype with different biofilm forming strengths were used to non-invasively infect mammary glands of lactating mice. Biofilm forming potential of these strains were determined by tissue culture plate method, ica typing and virulence gene profile per detection by PCR. Delivery of the infectious dose of S. aureus was directly through the teat lactiferous duct without invasive scraping of the teat surface. Both bacteriological and histological methods were used for analysis of mammary gland pathology of mice post-infection. Histopathological analysis of the infected mammary glands revealed that mice inoculated with the strong biofilm forming S. aureus strain produced marked acute mastitic lesions, showing profuse infiltration predominantly with neutrophils, with evidence of necrosis in the affected mammary glands. In contrast, the damage was significantly less severe in mammary glands of mice infected with the weak biofilm-forming S. aureus strain. Although both IL-1β and TNF-α inflammatory biomarkers were produced in infected mice, level of TNF-α produced was significantly higher (p<0.05) in mice inoculated with strong biofilm forming S. aureus than the weak biofilm forming strain. This finding suggests an important role of TNF-α in mammary gland pathology post-infection with strong biofilm-forming S. aureus in the acute mouse mastitis model, and offers an opportunity for the development of novel strategies for reduction of mammary tissue damage, with or without use of antimicrobials and/or anti-inflammatory compounds for the treatment of bovine mastitis.


Endothelial dysfunction and xanthine oxidoreductase activity in rats with human renin and angiotensinogen genes.
We examined whether xanthine oxidoreductase (XOR), a hypoxia-inducible enzyme capable of generating reactive oxygen species, is involved in the onset of angiotensin (Ang) II-induced vascular dysfunction in double-transgenic rats (dTGR) harboring human renin and human angiotensinogen genes. In 7-week-old hypertensive dTGR, the endothelium-mediated relaxation of noradrenaline (NA)-precontracted renal arterial rings to acetylcholine (ACh) in vitro was markedly impaired compared with Sprague Dawley rats. Preincubation with superoxide dismutase (SOD) improved the endothelium-dependent vascular relaxation, indicating that in dTGR, endothelial dysfunction is associated with increased superoxide formation. Preincubation with the XOR inhibitor oxypurinol also improved endothelium-dependent vascular relaxation. The endothelium-independent relaxation to sodium nitroprusside was similar in both strains. In dTGR, serum 8-isoprostaglandin F(2alpha), a vasoconstrictor and antinatriuretic arachidonic acid metabolite produced by oxidative stress, was increased by 100%, and the activity of XOR in the kidney was increased by 40%. Urinary nitrate plus nitrite (NO(x)) excretion, a marker of total body NO generation, was decreased by 85%. Contractile responses of renal arteries to Ang II, endothelin-1 (ET-1), and NA were decreased in dTGR, suggesting hypertension-associated generalized changes in the vascular function rather than a receptor-specific desensitization. Valsartan (30 mg/kg PO for 3 weeks) normalized blood pressure, endothelial dysfunction, and the contractile responses to ET-1 and NA. Valsartan also normalized serum 8-isoprostaglandin F(2alpha) levels, renal XOR activity, and, to a degree, NO(x) excretion. Thus, overproduction of Ang II in dTGR induces pronounced endothelial dysfunction, whereas the sensitivity of vascular smooth muscle cells to nitric oxide is unaltered. Ang II-induced endothelial dysfunction is associated with increased oxidative stress and vascular xanthine oxidase activity.


Pregnancy and parenting support for youth experiencing homelessness.
This study explored the perceptions and experiences related to pregnancy and parenting support among youth while homeless. This study employed a qualitative descriptive design using data collected from focus group discussions. We assessed the experiences and perceptions of youth related to pregnancy and parenting support. Eighty-one youth participated in eight focus group discussions and were recruited from shelters, drop-in centers, and organizations that serve youth in a large metropolitan areas in the southern United States. Thematic content analyses were used to generate results from the qualitative data. Four main themes emerged: youth encountered barriers to accessing healthcare services at the individual and system levels; pregnancy and parenting are stressful, especially during homelessness; support can help overcome the stresses of parenting; and embracing responsibility or "stepping up" is a positive influence of pregnancy and parenting during homelessness. Youth experiencing homelessness (YEH) face significant challenges to accessing healthcare services and adjusting to the parental role. Interventions for pregnant and parenting youth should be co-designed with and tailored for youth and address the existing health inequities within the healthcare and social service systems.


Effects of hyperglycemia on bone metabolism and bone matrix in goldfish scales.
Increased risk of fracture associated with type 2 diabetes has been a topic of recent concern. Fracture risk is related to a decrease in bone strength, which can be affected by bone metabolism and the quality of the bone. To investigate the cause of the increased fracture rate in patients with diabetes through analyses of bone metabolism and bone matrix protein properties, we used goldfish scales as a bone model for hyperglycemia. Using the scales of seven alloxan-treated and seven vehicle-treated control goldfish, we assessed bone metabolism by analyzing the activity of marker enzymes and mRNA expression of marker genes, and we measured the change in molecular weight of scale matrix proteins with SDS-PAGE. After only a 2-week exposure to hyperglycemia, the molecular weight of α- and β-fractions of bone matrix collagen proteins changed incrementally in the regenerating scales of hyperglycemic goldfish compared with those of euglycemic goldfish. In addition, the relative ratio of the γ-fraction significantly increased, and a δ-fraction appeared after adding glyceraldehyde-a candidate for the formation of advanced glycation end products in diabetes-to isolated type 1 collagen in vitro. The enzymatic activity and mRNA expression of osteoblast and osteoclast markers were not significantly different between hyperglycemic and euglycemic goldfish scales. These results indicate that hyperglycemia is likely to affect bone quality through glycation of matrix collagen from an early stage of hyperglycemia. Therefore, non-enzymatic glycation of collagen fibers in bone matrix may lead to the deterioration of bone quality from the onset of diabetes.


Human eosinophils express transforming growth factor alpha.
Transforming growth factor alpha (TGF-alpha) is a pleuripotential cytokine with diverse biological effects, including the ability to influence the proliferation of normal cells or neoplastic epithelial cells. Eosinophils are a subset of granulocytes that normally enter the peripheral tissues, particularly those beneath gastrointestinal, respiratory, and urogenital epithelium, where they reside in close proximity to the epithelial elements. In this study, we demonstrate that the great majority of eosinophils infiltrating the interstitial tissues adjacent to two colonic adenocarcinomas and two oral squamous cell carcinomas labeled specifically by in situ hybridization with a 35S-riboprobe for human TGF-alpha (hTGF-alpha). No other identifiable leukocytes in these lesions contained detectable hTGF-alpha mRNA. We also examined leukocytes purified from a patient with the idiopathic hypereosinophilic syndrome. 80% of these eosinophils, but none of the patient's neutrophils or mononuclear cells, were positive for hTGF-alpha mRNA by in situ hybridization, and 55% of these eosinophils were positive by immunohistochemistry with a monoclonal antibody directed against the COOH terminus of the mature hTGF-alpha peptide. Finally, the identification of the purified eosinophil-associated transcript as hTGF-alpha was confirmed by polymerase chain reaction product restriction enzyme analysis followed by Southern blot hybridization. In contrast to eosinophils from the patient with hypereosinophilic syndrome, the peripheral blood eosinophils from only two of seven normal donors had detectable TGF-alpha mRNA and none of these eosinophils contained immunohistochemically detectable TGF-alpha product. Taken together, these findings establish that human eosinophils can express TGF-alpha, but suggest that the expression of TGF-alpha by eosinophils may be under microenvironmental regulation. Demonstration of TGF-alpha production by tissue-infiltrating eosinophils and the eosinophils in the hypereosinophilic syndrome identifies a novel mechanism by which eosinophils might contribute to physiological, immunological, and pathological responses.


Specimen Temperature Detection on a Clinical Laboratory Pre-Analytic Automation Track: Implications for Direct-from-Track Total Laboratory Automation (TLA) Systems.
Clinical laboratory regulations require temperature monitoring of facilities, reagent and specimen storage, as well as temperature-dependent equipment. Real-time specimen temperature detection has not yet been integrated into total laboratory automation (TLA) solutions. An infrared (IR) pyrometer was paired with a complementary metal oxide semiconductor (CMOS) laser sensor and connected to an embedded networked personal computer (PC) to create a modular temperature detection unit for closed, moving clinical laboratory specimens. Accuracy of the detector was assessed by comparing temperature measurements to those obtained from thermocouples connected to battery-operated data loggers. The temperature detector was then installed on a pre-analytic laboratory automation system to assess specimen temperature before and after processing on an integrated thawing and mixing (T/M) robotic workcell. The IR temperature detector was able to accurately record temperature of closed, moving specimens on a pre-analytic automation system. The effectiveness of the T/M workcell was independently verified using the temperature detector. Specimen reroute on the pre-analytic automation track was identified as a potential risk for frozen specimens being inadvertently delivered to future, connected instrumentation. Automated IR temperature detection can be used to verify specimen temperature prior to instrument loading and/or sampling. Such systems could be used to prevent frozen specimens from being inadvertently loaded onto analytical instrumentation in TLA solutions.


Supporting aboriginal knowledge and practice in health care: lessons from a qualitative evaluation of the strong women, strong babies, strong culture program.
The Strong Women, Strong Babies, Strong Culture Program (the Program) evolved from a recognition of the value of Aboriginal knowledge and practice in promoting maternal and child health (MCH) in remote communities of the Northern Territory (NT) of Australia. Commencing in 1993 it continues to operate today. In 2008, the NT Department of Health commissioned an evaluation to identify enabling factors and barriers to successful implementation of the Program, and to identify potential pathways for future development. In this paper we focus on the evaluation findings related specifically to the role of Aborignal cultural knowledge and practice within the Program. A qualitative evaluation utilised purposive sampling to maximise diversity in program history and Aboriginal culture. Semi-structured, in-depth interviews with 76 participants were recorded in their preferred language with a registered Interpreter when required. Thematic analysis of data was verified or modified through further discussions with participants and members of the evaluation team. Although the importance of Aboriginal knowledge and practice as a fundamental component of the Program is widely acknowledged, there has been considerable variation across time and location in the extent to which these cultural dimensions have been included in practice. Factors contributing to this variation are complex and relate to a number of broad themes including: location of control over Program activities; recognition and respect for Aboriginal knowledge and practice as a legitimate component of health care; working in partnership; communication within and beyond the Program; access to transport and working space; and governance and organisational support. We suggest that inclusion of Aboriginal knowledge and practice as a fundamental component of the Program is key to its survival over more than twenty years despite serious challenges. Respect for the legitimacy of Aboriginal knowledge and practice within health care, a high level of community participation and control supported through effective governance and sufficient organisational commitment as well as competence in intercultural collaborative practice of health staff are critical requirements for realising the potential for cultural knowledge and practice to improve Aboriginal health outcomes.


Effects of unilateral stellate ganglion stimulation and ablation on electrophysiologic changes induced by acute myocardial ischemia in dogs.
We recorded direct-current extracellular electrograms simultaneously from 60 left ventricular epicardial sites in 38 alpha-chloralose-anesthetized dogs during repeated, 5 min coronary arterial occlusions. In each dog recordings made during control occlusions were compared with those made in occlusions after, or during, the following interventions on the sympathetic nervous system: left stellate ganglion stimulation, left stellectomy, right stellectomy, and clamping the abdominal aorta with intact sympathetic nerves to induce a rise of blood pressure equal to that present during left stellate stimulation. Heart rate was kept constant. Measurements included determination of TQ segment potentials and times of local activation. After 2 min of ischemia, the degree of TQ segment depression was increased by left stellate ganglion stimulation and was decreased by both left stellectomy and clamping the aorta. Also, the area showing negative TQ potentials, indicating decreased resting membrane potentials, was enlarged by both left stellate stimulation and right stellectomy and reduced by left stellectomy. No differences were found in the results of experiments in which the left anterior descending coronary artery was occluded and those in which the circumflex branch was occluded. Left stellate stimulation significantly improved conduction within the ischemic zone. No evidence was found to suggest that the arrhythmogenic effects of left stellate stimulation and of right stellectomy, confirmed in the present study, resulted from an increased likelihood for reentry in the subepicardium of the ischemic zone.


The use and role of sport chiropractors in the national football league: a short report.
To analyze chiropractic utilization on National Football League (NFL) medical teams and the role played by chiropractors. Postal survey of head athletic trainers of the 36 teams. Survey questions were developed from responses to a questionnaire submitted to a pilot group of 30 sport chiropractors and a panel of 20 postdoctoral faculty of the sport chiropractic program of the American Chiropractic Board of Sport Physicians, as well as a representative from the University of South Alabama. Twenty-two of 36 questionnaires were returned for a return rate of 66%. Of the trainers who did respond, 45% have personally been treated by a chiropractor, and 55% have not. Seventy-seven percent of the trainers have referred to a chiropractor for evaluation or treatment, and 23% have not. Thirty-one percent of NFL teams use a chiropractor in an official capacity on their staffs, and 69% do not. When asked to identify conditions appropriate for referral to a chiropractor, the respondents identified low back pain (61%), "stingers" and "burners" usually associated with neck injury (31%), headaches (8%), asthma or other visceral disorders (0%). All respondents (100%) agree that some players use chiropractic care without referral from team medical staff. There is significant chiropractic participation in US professional football. Certified athletic trainers see a role for the sport chiropractor in the NFL, primarily as a spinal specialist treating low back and other musculoskeletal injuries. A substantial majority of NFL trainers have developed cooperative relationships with chiropractors, with 77% having referred a player to a chiropractor. Thirty-one percent of NFL teams have a chiropractor officially on staff, and an additional 12% of teams refer players to chiropractors but do not directly retain these chiropractors.


Viability of Salmonella typhimurium in different environmental conditions (feed, litter; temperature).
In countries with a prevailing poultry production, salmonellosis is of growing importance. The poultry contaminated with salmonellae plays a significant role in the food poisoning of men and in decreasing the breeding results. The study investigated the viability of Salmonella typhimurium in feed and litter contaminated with this germ, at different temperatures. The organism remained viable at 37 degrees C in feed up to 6 weeks, in litter for 2 weeks, at room temperature in the feed up to 71 weeks in the litter up to 78 weeks, and at 7 degrees C in feed and litter up to 79 weeks. Recommendations are given for the control of salmonellosis by referring to the sources and possibilities of contamination.


A Bio-logical Approach to Catalysis in the Pharmaceutical Industry.
Enzymes have the potential to catalyse complex chemical reactions with unprecedented selectivity, under mild conditions in aqueous media. Accordingly, there is serious interest from the pharmaceutical industry to utilize enzymes as biocatalysts to produce medicines in an environmentally sustainable and economic manner. Prominent advances in the field of biotechnology have transformed this potential into a reality. Using modern protein engineering techniques, in a matter of months it is possible to evolve an enzyme, which fits the demands of a chemical process, or even to catalyse entirely novel chemistry. Consequently, biocatalysis is routinely applied throughout the pharmaceutical industry for a variety of applications, ranging from the manufacture of large volumes of high value blockbuster drugs to expanding the chemical space available for drug discovery.


Relationship between lymphoscintigraphy and clinical findings in lower limb lymphedema (LO): toward a comprehensive staging.
Although radionuclide lymphoscintigraphy (RNL) is widely used diagnostically for patients with lymphedema (LE), it has not been utilized for LE staging, which is still based upon clinical findings. The aim of this work is to establish whether the results of both conventional RNL and fusion imaging obtained from hybrid detectors may be used for a comprehensive clinicoimaging staging in LE. Radiolabeled nanocolloids (0.2 ml) were subcutaneously injected in 4,328 patients (23-78 years) with clinical lower limb LE and without venous disease. Patients were classified according to the ISL classification and had a minimal follow-up of 2 years. Images were taken 60 minutes after the injection as a whole body scanning and fusion images of functional SPET and anatomical CT. Clinical and RNL results were not in accordance, and a specific RNL staging was established. The association of clinical and functional staging yields a new method to grade LE patients, and this staging correlated with treatment efficacy. RNL is an important tool in lymphology, and its association with the clinical evaluation offers a new grading system which may be able to delineate patients with good prognosis, patients at risk for a complex decongestive physiotherapy (CDP) failure, and patients who may benefit from other therapeutic protocols.