Functional results of posterior tibial tendon reconstruction, calcaneal osteotomy, and gastrocnemius recession.
This study aimed to assess and provide prospective outcome data following reconstruction of Stage II posterior tibial tendon insufficiency, as well as evaluate the effect of reconstruction with gastrocnemius recession on plantarflexion strength. A prospective evaluation of 24 patients undergoing reconstruction for Stage II posterior tibial tendon insufficiency was granted IRB approval. The reconstructive procedures consisted of a flexor digitorum longus transfer, medial displacement calcaneal osteotomy, lateral column lengthening, and gastrocnemius recession. Patients were asked to complete multiple outcome measures preoperatively, 6 months, 1 year, and 2 years postoperatively. A dynamometer was utilized to evaluate peak torque plantarflexion preoperatively, 6 months, and 1 year postoperatively. In the study, 14 patients completed preoperative surveys, and 23 patients had 2-year followup. Patients were highly satisfied with the results of their surgery. All outcome measures showed statistically significant improvement. Improvement was seen at 6 months, but results continued to improve at the 1-year mark. By the second year, improvement largely reached a plateau. Biodex testing showed no loss of plantarflexion strength after reconstruction and gastrocnemius recession. Reconstruction of the flexible adult acquired flatfoot with FDL transfer, double calcaneal osteotomy, and gastrocnemius recession yielded excellent functional results for the treatment of Stage II posterior tibial tendon insufficiency. Plantarflexion weakness was not found to be a concern. A good functional outcome can be anticipated after the early postoperative period. However, it should be expected to take at least 1 year for maximal benefit.


Simultaneous feature selection and outlier detection with optimality guarantees.
Biomedical research is increasingly data rich, with studies comprising ever growing numbers of features. The larger a study, the higher the likelihood that a substantial portion of the features may be redundant and/or contain contamination (outlying values). This poses serious challenges, which are exacerbated in cases where the sample sizes are relatively small. Effective and efficient approaches to perform sparse estimation in the presence of outliers are critical for these studies, and have received considerable attention in the last decade. We contribute to this area considering high-dimensional regressions contaminated by multiple mean-shift outliers affecting both the response and the design matrix. We develop a general framework and use mixed-integer programming to simultaneously perform feature selection and outlier detection with provably optimal guarantees. We prove theoretical properties for our approach, that is, a necessary and sufficient condition for the robustly strong oracle property, where the number of features can increase exponentially with the sample size; the optimal estimation of parameters; and the breakdown point of the resulting estimates. Moreover, we provide computationally efficient procedures to tune integer constraints and warm-start the algorithm. We show the superior performance of our proposal compared to existing heuristic methods through simulations and use it to study the relationships between childhood obesity and the human microbiome.


Infertile couples' experience of family stress while women are hospitalized for ovarian hyperstimulation syndrome during infertility treatment.
The aim of this study was to explore the essential structure of family stress among hospitalized women receiving infertility treatment with Ovarian Hyperstimulation Syndrome. When hospitalization is necessary for infertile women with Ovarian Hyperstimulation Syndrome, they face health-illness transition stress and their families are traumatized by the pressure of hospitalization. Most literature on infertility treatment has dealt with the infertile women's physio-psychological reactions, the impact on the couples' relationships and the influence of social support on infertile couples. A descriptive phenomenological design consistent with Husserl's philosophy. Ten married couples from a Taipei medical centre participated in the study. All the couples were receiving infertility treatment because the female partners were suffering from moderate or severe Ovarian Hyperstimulation Syndrome and this required hospitalized. An open in-depth interview technique encouraged parents to reflect on their experience, which raised their feelings to a conscious level. Data were analysed using Colaizzi's approach. This study explored infertile women's experiences from the couples' perspectives and the results identify the overall stresses that the family face. Five themes emerged from the study, namely, the stress of 'carrying on the ancestral line', the psychological reactions of the couple, a disordering of family life, reorganization of family life and external family support. The results demonstrate that the experience of family stress involves impacts that range across the domains of individual, marital, family and social interactions and there is a need to cope with these when the wife is hospitalized for moderate to severe Ovarian Hyperstimulation Syndrome. The findings indicated that nurses should provide infertile couples with family-centred perspectives that are related to Chinese cultural family values. Nurses should supply information on infertility treatment and assist couples to cope with their personal and family stress.


Tracking Health Related Discussions on Reddit for Public Health Applications.
We use Reddit to demonstrate social media's potential for public health applications. First, we employ a lexicon-based approach to track the prevalence of keywords indicating public interest in Ebola, electronic cigarette, influenza, and marijuana. Second, to better understand the public reactions, we use the Latent Dirichlet Allocation algorithm, to identify either the general themes or motivations for extreme changes in the volume of discussion over time. We observe that discussions related to Ebola and influenza, infectious diseases of public health interests, surged when the first case of Ebola was diagnosed and a new strain of H1N1 influenza virus was confirmed in the United States. We also observed that discussions of a controversial health topic like marijuana increased with the announcement of a major change in United States federal policy. Discussions of electronic cigarette highlighted opportunities for better health education. Lastly, we discuss the implications of our findings for utilizing Reddit data for public health applications.


Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 revision.
Allergic rhinitis represents a global health problem affecting 10% to 20% of the population. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines have been widely used to treat the approximately 500 million affected patients globally. To develop explicit, unambiguous, and transparent clinical recommendations systematically for treatment of allergic rhinitis on the basis of current best evidence. The authors updated ARIA clinical recommendations in collaboration with Global Allergy and Asthma European Network following the approach suggested by the Grading of Recommendations Assessment, Development and Evaluation working group. This article presents recommendations about the prevention of allergic diseases, the use of oral and topical medications, allergen specific immunotherapy, and complementary treatments in patients with allergic rhinitis as well as patients with both allergic rhinitis and asthma. The guideline panel developed evidence profiles for each recommendation and considered health benefits and harms, burden, patient preferences, and resource use, when appropriate, to formulate recommendations for patients, clinicians, and other health care professionals. These are the most recent and currently the most systematically and transparently developed recommendations about the treatment of allergic rhinitis in adults and children. Patients, clinicians, and policy makers are encouraged to use these recommendations in their daily practice and to support their decisions.


A dimensionality reduction technique based on a least squared error criterion.
A method of achieving dimensionality reduction is presented. The reduced dimensionality is achieved by utilizing a least squared error technique under the assumption that the goodness criterion is the maximum separation of classes. The criterion is met by first maximizing the spread of the cluster centers, and then minimizing the within class scatter. The derivation of the desired transformation from an arbitrary p-space to a space of lower dimension, say l, is completed with the assumption that the cluster centers are known. The criterion for the cluster center location is the minimization of the variance of the distance between the cluster center and the transformed pattern. It is demonstrated that the resulting cluster center set is similar to the simplex signal set in communication theory, which is a minimum energy signal set.


Decision making in trauma settings: simulation to improve diagnostic skills.
In the setting of acute injury, a wrong, missed, or delayed diagnosis can impact survival. Clinicians rely on pattern recognition and heuristics to rapidly assess injuries, but an overreliance on these approaches can result in a diagnostic error. Simulation has been advocated as a method for practitioners to learn how to recognize the limitations of heuristics and develop better diagnostic skills. The objective of this study was to determine whether simulation could be used to provide teams the experiences in managing scenarios that require the use of heuristic as well as analytic diagnostic skills to effectively recognize and treat potentially life-threatening injuries. Ten scenarios were developed to assess the ability of trauma teams to provide initial care to a severely injured patient. Seven standard scenarios simulated severe injuries that once diagnosed could be effectively treated using standard Advanced Trauma Life Support algorithms. Because diagnostic error occurs more commonly in complex clinical settings, 3 complex scenarios required teams to use more advanced diagnostic skills to uncover a coexisting condition and treat the patient. Teams composed of 3 to 5 practitioners were evaluated in the performance of 7 (of 10) randomly selected scenarios (5 standard, 2 complex). Expert rates scored teams using standardized checklists and global scores. Eighty-three surgery, emergency medicine, and anesthesia residents constituted 21 teams. Expert raters were able to reliably score the scenarios. Teams accomplished fewer checklist actions and received lower global scores on the 3 analytic scenarios (73.8% [12.3%] and 5.9 [1.6], respectively) compared with the 7 heuristic scenarios (83.2% [11.7%] and 6.6 [1.3], respectively; P < 0.05 for both). Teams led by more junior residents received higher global scores on the analytic scenarios (6.4 [1.3]) than the more senior team leaders (5.3 [1.7]). This preliminary study indicates that teams led by more senior residents received higher scores when managing heuristic scenarios but were less effective when managing the scenarios that require a more analytic approach. Simulation can be used to provide teams with decision-making experiences in trauma settings and could be used to improve diagnostic skills as well as study the decision-making process.


Revising the self-report strengths and difficulties questionnaire for cross-country comparisons of adolescent mental health problems: the SDQ-R.
The Strengths and Difficulties Questionnaire (SDQ) has been used in many epidemiological studies to assess adolescent mental health problems, but cross-country comparisons of the self-report SDQ are scarce and so far failed to find a good-fitting, common, invariant measurement model across countries. The present study aims to evaluate and establish a version of the self-report SDQ that allows for a valid cross-country comparison of adolescent self-reported mental health problems. Using the Health Behaviour in School-aged Children study, the measurement model and measurement invariance of the 20 items of the self-report SDQ measuring adolescent mental health problems were evaluated. Nationally representative samples of 11-, 13- and 15-year old adolescents (n = 33 233) from seven countries of different regions in Europe (Bulgaria, Germany, Greece, the Netherlands, Poland, Romania, Slovenia) were used. In order to establish a good-fitting and common measurement model, the five reverse worded items of the self-report SDQ had to be removed. Using this revised version of the self-report SDQ, the SDQ-R, partial measurement invariance was established, indicating that latent factor means assessing conduct problems, emotional symptoms, peer relationships problems and hyperactivity-inattention problems could be validly compared across the countries in this study. Results showed that adolescents in Greece scored relatively low on almost all problem subscales, whereas adolescents in Poland scored relatively high on almost all problem subscales. Adolescents in the Netherlands reported the most divergent profile of mental health problems with the lowest levels of conduct problems, low levels of emotional symptoms and peer relationship problems, but the highest levels of hyperactivity-inattention problems. With six factor loadings being non-invariant, partial measurement invariance was established, indicating that the 15-item SDQ-R could be used in our cross-country comparison of adolescent mental health problems. To move the field of internationally comparative research on adolescent mental health forward, studies should test the applicability of the SDQ-R in other countries in- and outside Europe, continue to develop the SDQ-R as a cross-country invariant measure of adolescent mental health, and examine explanations for the found country differences in adolescent mental health problems.


Calcium release in skinned muscle fibres of the toad by transverse tubule depolarization or by direct stimulation.
1. Skeletal muscle fibres from the toad were mechanically skinned under paraffin oil and then bathed in a potassium HDTA solution (HDTA: hexamethylenediamine-tetraacetate) which mimicked the ionic composition of the myoplasm. 2. Rapid transient contractions could be triggered by substitution of K+ with Na+ (with no change of anion), which should have virtually no direct effect on the electrical polarization of the sarcoplasmic reticulum (SR) membrane. Up to thirty or more contractions could be evoked by repeated substitutions if there was sufficient 'repriming' time (about 30 s) between them; these rapid contractions were analagous to potassium contractures in intact fibres. 3. When the SR was not heavily loaded, substitution of potassium HDTA with choline chloride also produced a rapid, brief contraction. 4. All treatments designed to 'inactivate' the voltage sensor in the T-system invariably abolished the rapid contractions. Thus, rapid contractions were absent if (i) the T-system was permanently depolarized by pre-soaking the muscle in a high potassium solution with ouabain before skinning, (ii) a fibre was split rather than skinned, (iii) the T-system was temporarily depolarized by Na+ substitution immediately before choline chloride substitution, or vice versa, (iv) a skinned fibre was briefly exposed to saponin (50 micrograms/ml) to selectively disrupt the T-system membrane or (v) the muscle was pre-soaked in a solution with 1 mM-EGTA and no Ca2+ or Mg2+ before skinning. In contrast to (v), if 10 mM-Mg2+ was present in the EGTA solution before skinning, rapid contractions could be elicited, presumably because the presence of Mg2+ prevented the inactivation of the T-system voltage sensor in low [Ca2+]. 5. These results unequivocally demonstrate that (a) the T-system reseals and repolarizes after mechanical skinning under oil and (b) the fast contractions are produced by activation of the voltage sensor in the T-system. 6. When the SR had been heavily loaded, choline chloride substitution (but not Na+ substitution) could also induce an unphysiological, slow contraction ('second component'). In total contrast to the fast contraction, this slow component was unaffected by any of the treatments (i-v) above, indicating that it did not depend on activation of the voltage sensor in the T-system but resulted from a direct action of choline chloride on the SR.(ABSTRACT TRUNCATED AT 400 WORDS)


Association between COVID-19 infection and herpes zoster: A case series.
Herpes zoster (HZ) is a manifestation of the reactivation of latent varicella zoster virus (VZV) infection in the dorsal root ganglion. The occurrence of HZ has been reported in association with COVID-19. Herein, we describe 10 cases who developed classic HZ within 2-3 weeks of acquiring COVID-19 infection. The triggers in these patients could be severe stress (related to quarantine issues, fear of hospitalisation and death) immune dysregulation and systemic steroid therapy in treating COVID-19. The clinical patterns and therapeutic responses observed were similar to HZ in immunocompetent persons. Increased expression of NKG2A on NK and CD8+ T cells has been proposed as a pathophysiologic mechanism in triggering HZ at the molecular level in COVID-19 patients. Primary physicians should be aware of this association to counsel and treat such patients appropriately, as initiating early treatment could minimise the risk of complications like postherpetic neuralgia.


Does levothyroxine administration impact parathyroid localization?
Proper localization is crucial in performing minimally invasive parathyroidectomy for primary hyperparathyroidism. Ultrasonography (US) and Tc-99m sestamibi (MIBI) scintigraphy are common methods used for localization. As the appearance and activity of the thyroid gland may impact parathyroid localization, the purpose of this study was to determine how exogenous use of the thyroid hormone, levothyroxine (LT), affects parathyroid localization. Adult patients with non-familial primary hyperparathyroidism who underwent initial parathyroidectomy from 2000-2014 were retrospectively identified. LT (+LT) and non-LT (-LT) patients were matched 1:3 based on age, gender, goiter status, and preoperative parathyroid hormone levels. Subgroup analysis was performed on patients previously treated with radioactive iodine and patients undergoing single adenoma resection. Of the 1737 patients that met inclusion criteria, 286 were on LT at the time of their parathyroid localization scan. Use of LT did not impact the percentage of correct MIBI localization scans when compared with -LT patients (P = 0.83). Interestingly, use of LT significantly hindered localization by US in comparison with the -LT group (48.4 versus 62.2%, P < 0.01). When examining only patients where a single upper gland was removed, the +LT group was less likely to have a correct US compared with the -LT group (50 versus 72.8%, P < 0.01). However, there was no difference in US accuracy for patients who only had a single lower gland removed (P = 0.51). Exogenous LT is associated with impaired parathyroid localization with US but not MIBI. Surgeons should be aware of localization efficiency for this subset of patients in the era of personalized medicine and cost effectiveness.


Effect of heat treatment of bovine colostrum on bacterial counts, viscosity, and Immunoglobulin G concentration.
A study was conducted to identify the optimal temperature and time at which heat treatment of bovine colostrum would least change viscosity and IgG concentrations yet reduce bacterial count. First-milking colostrum with >50g of immunoglobulins/L (measured by colostrometer) was collected from 30 Holstein cows. Aliquots of colostrum were heated for 0, 30, 60, or 90min at 57, 60, or 63 degrees C in a water bath. Samples were examined for viscosity, IgG(1), and IgG(2) concentrations, standard plate count, coagulase-negative staphylococci, environmental streptococci, coliform, gram-negative noncoliform, Streptococcus agalactiae, and Staphylococcus aureus counts. All heat treatments reduced counts of all bacteria groups measured compared with untreated colostrum samples. Heat treatment at >or=60 degrees C denatured IgG(1) compared with untreated colostrum; however, colostral IgG(2) levels were not reduced when temperature was held at 60 degrees C for <60min. Viscosity was not affected when temperature was held at 60 degrees C for <60min. In this study, heat treatment of bovine colostrum at 60 degrees C for 30 or 60min reduced bacterial count, slightly reduced IgG concentration, and did not affect viscosity.


Curriculum structure and the European Credit Transfer System for European dental schools: part I.
This paper presents a proposed curriculum structure and system of European Credit Transfer (ECTS) for undergraduate dental schools throughout Europe. It is the result of the work of a Taskforce ('Taskforce II'), appointed by DentEd, a thematic network of European dental schools and the Association for Dental Education in Europe (ADEE). There has been pan-European discussion of the document in draft stages (it was distributed to 200 dental schools) and following amendment, it was agreed formally at the National Assembly of ADEE in Athens, Greece, in September 2005. The main elements of the paper relate to: (i) a description of the framework proposed with relevance to the Bologna recommendations and common directive on recognition for professional qualifications as they apply to Dentistry; (ii) the structure of an undergraduate dental curriculum; (iii) student exchange and ECTS. In addition, the paper presents a series of requirements, guidelines and recommendations for action. ADEE expects that the 'requirements' proposed will be followed by dental schools in Europe, whilst the 'guidelines' and 'recommendations' also provided are open to local interpretation. The paper is also published on the ADEE website.


[Response to treatment with tyrosine kinase inhibitors in chronic myeloid leukemia].
Chronic myeloid leukemia represents 15 % of all the leukemias in adults. With the introduction of tyrosine kinase inhibitors, overall survival at 10 years is 80-90 %. The objective was to describe the epidemiology, complete cytogenetic response and major molecular response with tyrosine kinase inhibitors in patients with chronic myeloid leukemia. It was performed a descriptive cross-sectional study of patients with chronic myeloid leukemia and Philadelphia chromosome-positive in treatment with tyrosine kinase inhibitors. The sample included 54 patients with a mean age of 41 years; 78 % of patients were in chronic phase, and in 8 % of patients were identified complex karyotype at diagnosis. All patients received imatinib as first-line treatment. We identified mutations in 8 %. The patients with primary or secondary resistance (30%) received second-generation tyrosine kinase inhibitors as a second-line therapy. Of 35 patients treated with imatinib, 23 had complete cytogenetic response, 23 had major molecular response, and 16 had loss of response to treatment. Of nine patients treated with nilotinib, two presented complete cytogenetic response, two major molecular response, and five loss of response to treatment. Of seven patients treated with dasatinib, two had complete cytogenetic response, two major molecular response, and four loss of response to treatment. Of patients studied, 30 % was resistant to imatinib, 52 % achieved a complete cytogenetic response, and 42 % major molecular response. The use of second generation tyrosine kinase inhibitors led to obtain a complete cytogenetic and major molecular response in fewer time.


Cellular effects of everolimus and sirolimus on podocytes.
Everolimus (EVL) and Sirolimus (SRL) are potent immunosuppressant agents belonging to the group of mammalian target of rapamycin (mTOR) inhibitors used to prevent transplant rejection. However, some patients develop proteinuria following a switch from a calcineurin inhibitor regimen to mTOR inhibitors. Whether different mTOR inhibitors show similar effects on podocytes is still unknown. To analyze this, human podocytes were incubated with different doses of EVL and SRL. After incubation with EVL or SRL, podocytes revealed a reduced expression of total mTOR. Phosphorylation of p70S6K and Akt was diminished, whereas pAkt expression was more reduced in the SRL group. In both groups actin cytoskeletal reorganization was increased. Synaptopodin and podocin expression was reduced as well as nephrin protein, particularly in the SRL group. NFκB activation and IL-6 levels were lower in EVL and SRL, and even lower in SRL. Apoptosis was more increased in SRL than in the EVL group. Our data suggests that mTOR inhibitors affect podocyte integrity with respect to podocyte proteins, cytoskeleton, inflammation, and apoptosis. Our study is the first to analyze both mTOR inhibitors, EVL and SRL, in parallel in podocytes. Partially, the impact of EVL and SRL on podocytes differs. Nevertheless, it still remains unclear whether these differences are of relevance regarding to proteinuria in transplant patients.


Cloning and expression of the fhu genes involved in iron(III)-hydroxamate uptake by Escherichia coli.
Each of the four hydroxamate compounds, ferrichrome, aerobactin, rhodotorulic acid, and coprogen, known to transport ferric iron into Escherichia coli requires a specific outer membrane receptor protein. In addition, common transport functions for all four ferric hydroxamate compounds have been identified in the 3.5-min region of the linkage map and designated fhu. The fhu region was cloned into pBR322. By restriction analysis, Tn5 insertion mutations, and complementation studies between plasmid fragments and chromosomal mutants at least four loci in the order fhuA fhuC fhuD fhuB were found. The genetic products were determined in maxicells and minicells. fhuA codes for the known 78,000-dalton receptor protein and the 81,000-dalton precursor in the outer membrane, fhuC codes for a 30,000-dalton protein, and fhuD encodes a 26,000-dalton protein in the cytoplasmic membrane. No protein(s) could be assigned to the fhuB region. Truncated proteins derived from partial fhuA genes (68,000, 42,000, and 39,000 daltons) and a partial fhuD gene (24,000 daltons) and the strong polar effect on the expression of the genes indicated the direction of transcription to be from fhuA to fhuD.


High Energy Resolution Hyperspectral X-Ray Imaging for Low-Dose Contrast-Enhanced Digital Mammography.
Contrast-enhanced digital mammography (CEDM) is an alternative to conventional X-ray mammography for imaging dense breasts. However, conventional approaches to CEDM require a double exposure of the patient, implying higher dose, and risk of incorrect image registration due to motion artifacts. A novel approach is presented, based on hyperspectral imaging, where a detector combining positional and high-resolution spectral information (in this case based on Cadmium Telluride) is used. This allows simultaneous acquisition of the two images required for CEDM. The approach was tested on a custom breast-equivalent phantom containing iodinated contrast agent (Niopam 150®). Two algorithms were used to obtain images of the contrast agent distribution: K-edge subtraction (KES), providing images of the distribution of the contrast agent with the background structures removed, and a dual-energy (DE) algorithm, providing an iodine-equivalent image and a water-equivalent image. The high energy resolution of the detector allowed the selection of two close-by energies, maximising the signal in KES images, and enhancing the visibility of details with the low surface concentration of contrast agent. DE performed consistently better than KES in terms of contrast-to-noise ratio of the details; moreover, it allowed a correct reconstruction of the surface concentration of the contrast agent in the iodine image. Comparison with CEDM with a conventional detector proved the superior performance of hyperspectral CEDM in terms of the image quality/dose tradeoff.


Long-term oxygen therapy.
Long-term oxygen therapy (LTOT) has been shown to reduce pulmonary hypertension and improve survival in patients with chronic obstructive pulmonary disease and resting hypoxemia (reduced arterial partial pressure of oxygen ≤55 mmHg). However, the benefit of its use for chronic pulmonary diseases other than chronic obstructive pulmonary disease as well as for nonpulmonary conditions is debatable. Its role in patients with mild hypoxemia (reduced arterial partial pressure of oxygen >55 mmHg at rest) is presently being investigated in the LOTT. A meta-analysis of four controlled trials reporting the role of LTOT in patients with either nocturnal desaturation or daytime moderate hypoxemia found no difference in survival between patients on LTOT than those without. Advances in oxygen delivery and conservation devices have made domiciliary oxygen therapy more practical and popular for patients. There still remain concerns with the actual compliance of therapy among the needy patients.


Factors affecting health-promoting lifestyle profile in Iranian male seafarers working on tankers.
Seafaring is a risky occupation that is associated with a high incidence of lifestyle-related diseases. The present study was carried out to examine health promotion behaviour and its associated factors in seafarers of the National Iranian Tanker Company. A cross-sectional study was performed on 200 Iranian male seafarers in 2015. A self-administered socio-demographic and Health Promotion Lifestyle Profile II (HPLP-II) questionnaire was completed. One-way analysis of variance was used to identify significant differences among the various departments. The t-test was utilised to compare the HPLP-II scores according to the demographic variables. Multiple linear regression analysis was performed to assess the association between demographic variables and the overall HPLP-II score, in addition to the six health-promoting lifestyle subscale scores. The mean age of the participants was 35.93 ± 9.51 years. Most of the seafarers were categorised as having a moderate (32%) or good lifestyle (61.5%). The mean lifestyle score was 136.14 ± 19.90, with the subscale spiritual growth showing the highest score (26.16 ± 5.03) and the subscale exercise behaviour showing the lowest score (19.95 ± 4.23). The lowest score for nutrition was found among the seafarers working in the engine department (engine: 20.41 ± 4.50, deck: 23.52 ± 4.97, and galley: 24.83 ± 4.64) (p < 0.05). Working in the engine department was found to have a significant negative effect on the nutrition score (B = -3.57, p < 0.05). Moreover, educational level was found to have a significant positive effect on spiritual growth (B = 2.97, p < 0.05). The findings suggest that health-related issues in this occupation, especially workers in the engine room, are a matter of concern.


Monitoring of Blood Vessel Density Using Contrast-Enhanced High Frequency Ultrasound May Facilitate Early Diagnosis of Lymph Node Metastasis.
Time-dependent alterations in the ultrasonography characteristics of lymph nodes during early-stage metastasis have not been compared with those of tumor-draining lymph nodes that do not develop tumor; this is partly due to the absence of an appropriate experimental model. In a previous study of lymph nodes with experimental early-stage metastasis, we used contrast-enhanced high-frequency ultrasound to demonstrate that an increase in lymph node blood vessel density preceded any changes in lymph node volume. In the present study, we used an experimental model of lymph node metastasis in which tumor cells metastasized from the subiliac lymph node to the proper axillary lymph node (the tumor-draining lymph node). We utilized contrast-enhanced high-frequency ultrasound to perform a longitudinal analysis of tumor-draining lymph nodes, comparing those at an early-stage of metastasis with those that did not develop detectable metastasis. We found that the normalized blood vessel density of an early-stage metastatic lymph node exhibited a progressive rise, whereas that of a tumor-draining lymph node not containing tumor began to increase later. For both types of lymph nodes, the normalized blood vessel density on the final day of experiments showed a trend towards being higher than that measured in controls. We further found that mice with an initially low value for lymph node blood vessel density subsequently showed a larger increase in the blood vessel density of the metastatic lymph node; this differed significantly from measurements in controls. The present study indicates that a longitudinal analysis of the blood vessel densities of tumor-draining lymph nodes, made using contrast-enhanced high-frequency ultrasound imaging, may be a potentially promising method for detecting early-stage lymph node metastasis in selected patients. Furthermore, our findings suggest that tumor in an upstream lymph node may induce alteration of the vascular structures in draining lymph nodes that do not contain tumor.


Cerebrospinal Fluid Concentration of the RET Inhibitor Pralsetinib: A Case Report.
Pralsetinib is used to treat metastatic RET fusion-positive non-small cell lung cancer. Preclinical studies of pralsetinib have shown blood-brain barrier (BBB) penetration and intracranial activity. The intracranial efficacy of pralsetinib in patients with brain metastasis is considered to be greater compared to older multikinase tyrosine kinase inhibitors. However, CSF concentrations of pralsetinib in patients are not well described in the literature. We report a case of a patient with RET fusion-positive NSCLC treated with pralsetinib. Despite extracranial clinical and radiological remission, the patient developed progressive brain metastasis during treatment with pralsetinib. We measured the pralsetinib concentration in plasma and in CSF to determine the CSF-to-unbound plasma ratio. The measured pralsetinib concentrations in plasma and CSF were 1,951 ng/mL (∼57 unbound) and 14 ng/mL, respectively, reflecting a CSF-to-unbound plasma concentration ratio of 0.25. Our findings were compared with data from the literature. We showed that pralsetinib penetrates the CSF well and is expected to be an effective treatment for brain metastasis of RET fusion-positive NSCLC. Lack of intracranial efficacy is more likely to be caused by intrinsic or acquired tumor resistance instead of suboptimal exposure of pralsetinib in the brain.


Diclofenac induced gastrointestinal and renal toxicity is alleviated by thymoquinone treatment.
The aim of this study was to investigate whether thymoquinone (TQ) could alleviate diclofenac (DCLF)-induced gastrointestinal and renal toxicity in rats. Diclofenac was administered via intramuscular injection twice daily for 5 days and TQ was given by gavage for the same period. Hematological and biochemical profiles were measured with autoanalyzers while reactive oxygen/nitrogen species (ROS/RNS) generation and total antioxidant capacity (TAC) were assayed by standard kits. Tissue injuries were evaluated by microscopy and histopathological scoring. Diclofenac treatment caused kidney and liver function test abnormalities, reduced hematocrit and hemoglobin levels but increased WBC and platelet counts. Histopathological findings showed renal tubular damage, gastrointestinal lesions and increased fibrosis in DCLF treated rats. Thymoquinone administration, along with DCLF treatment, attenuated hematological test abnormalities and DCLF induced renal functional impairment as evident by significantly restored serum creatinine and blood urea nitrogen levels. Similarly, TQ treatment significantly alleviated liver function test abnormalities and decreased tissue injury in the stomach and duodenum. Diclofenac treatment caused increased ROS/RNS formation and decreased TAC in the kidney, stomach and duodenal tissue. Thymoquinone administration increased gastrointestinal and renal TAC in DCLF treated rats. These results indicate that TQ could ameliorate gastrointestinal and renal toxicity induced by high dose DCLF treatment.


Asthma care practices, perceptions, and beliefs of Chicago-area primary-care physicians. Chicago Asthma Surveillance Initiative Project Team.
Although primary-care physicians were a principal target audience for the National Asthma Education and Prevention Program (NAEPP), there is little published information describing the postguideline asthma care practices of these physicians or their willingness to embrace the NAEPP guidelines. This study examines asthma care practices of Chicago-area primary-care physicians and assesses these practitioners' perceptions and beliefs about several aspects of the NAEPP guidelines. In 1997, a self-administered survey was mailed to a randomly selected 10% sample of Chicago-area general pediatricians, internists, and family practitioners. Surveys were returned by 244 of the 405 eligible Chicago-area primary-care physicians (60.2%) in the sample. Of these, 66 (27.6%) were pediatricians, 83 (34.7%) were general internists, and 90 (37.7%) were family practitioners. Physicians reported that 54.6 +/- 2.7% (mean +/- SE) of patients with newly diagnosed asthma have spirometry performed as part of their initial evaluation. For patients with moderate persistent asthma, prescribing of inhaled corticosteroids varied by patient age, with 60.5% of physicians routinely prescribing them for patients < 5 years, compared with 95.7% of physicians prescribing them for patients > or = 5 years. Awareness of the NAEPP guide-lines among these physicians was high, with 88.5% reporting that they have heard of the guidelines, and 73.6% reporting having read them. Of patients with moderate or severe persistent asthma, physicians estimated that 47.7 +/- 2.7% were given written treatment plans. Several aspects of the NAEPP guidelines appear to have been incorporated into clinical practice by Chicago-area primary-care physicians, whereas other recommendations do not appear to have been readily adopted. This information suggests areas for interventions to improve primary care for asthma in the Chicago area.


Cholesterol oxides mediated changes in cytoskeletal organisation involves Rho GTPases.
The small GTPases Rho, Rac, and Cdc42 regulate the actin cytoskeleton in all eukaryotic cells. In this study we have evaluated the effect of cholesterol oxides (7-ketocholesterol and 25-hydroxycholesterol) on cell migration, cell adhesion, and cytoskeletal organisation of lens epithelial cells (LEC). Effects of cholesterol oxides on cytoskeleton were evaluated by immunofluorescence confocal microscopy. The 7-ketocholesterol induced cell arborisation, with bundling of vimentin and tubulin in the cell processes and formation of filopodia and stress fibres. Cells treated with 25-hydroxycholesterol showed a collapse of vimentin filaments towards the nucleus and formation of lamellipodia. In addition, cells treated with 7-ketocholesterol or 25-hydroxycholesterol showed decreased migration. The effects of cholesterol oxides on cytoskeletal proteins involve the activation of the small GTPases Rho, Rac, and Cdc42. Indeed, formation of both filopodia and stress fibres induced by 7-ketocholesterol is inhibited by overexpressing dominant negatives forms of Cdc42 and RhoA, respectively. Similarly, the collapse of vimentin intermediate filament network and the formation of lamellipodia, induced by 25-hydroxycholesterol, is inhibited by overexpressing dominant negatives forms of Rac1. The effects of cholesterol oxides described in this study for LEC are also observed for at least two other cell lines (H36CE and U373), suggesting that this may represent a general mechanism whereby cholesterol oxides induces cytoskeletal disorganisation.


Neural correlates of impaired volitional action control in schizophrenia patients.
Slowed initiation of volitional but not visually guided saccades indicates impaired volitional action control in schizophrenia patients (SZ). The present study aimed at identifying neural correlates of this specific deficit. Fourteen SZ and 13 healthy control participants (HC) underwent functional magnetic resonance imaging while performing volitional and visually guided saccades. SZ showed increased latencies in volitional but not in visually guided saccades. Brain activation during volitional saccades compared to visually guided saccades was increased in SZ compared to HC in several areas: the supplementary eye fields, suggesting inefficient production of volitional saccades; the prefrontal cortex, pointing to altered top down control on complex eye movements; and the left middle temporal area, suggesting changes in early sensory and attention processing during the volitional control of saccades in SZ.


Eye movements during visual search for emotional faces in individuals with chronic headache.
Attentional biases for pain-related information have been frequently reported in individuals with chronic pain. Recording of participants' eye movements provides a continuous measure of attention, although to date this methodology has received little use in research exploring attentional biases in chronic pain. The aim of the current investigation was to explore the specificity of attentional orienting bias using a novel visual search task while recording participant eye movement behaviours. This also allowed for the investigation of whether attentional biases for pain-related information exist in the presence of multiple stimuli competing for attention. Twenty-three participants with chronic headache and 24 pain-free, healthy control participants were engaged in a visual search task where pain, angry, happy and neutral faces were used as both target and distractor stimuli. While completing this task, participants' eye movements were recorded. Supporting the adopted hypothesis, participants with chronic headache, relative to healthy controls, demonstrated a significantly higher proportion of initial fixations to target pain expressions when the pain expressions were presented in displays containing neutral-distractor faces. No significant differences were found between groups in the time taken to fixate target pain expressions (localization time). Individuals with chronic headache show facilitated initial orienting towards pain expressions specifically when used as targets in a visual search task. This study adds to a growing body of research supporting the presence of pain-related attentional biases in chronic pain as assessed via different experimental paradigms, and shows biases to exist when multiple stimuli competing for attention are presented simultaneously.


Jumeaux, a novel Drosophila winged-helix family protein, is required for generating asymmetric sibling neuronal cell fates.
The great majority of neurons in the Drosophila embryonic CNS are generated through two successive asymmetric cell divisions; neuroblasts (NBs) divide to produce another NB and a smaller ganglion mother cell (GMC); GMCs divide to generate two sibling neurons which can adopt distinct identities. During the division of the first born GMC from the NB4-2 lineage, GMC4-2a, Inscuteable (Insc) is localised to the apical cortex, Pon/Numb is localised to the basal cortex and two daughters with distinct identities, the RP2 motoneuron and its sibling RP2sib, are born. Resolution of distinct sibling neuronal fates requires correct apical localisation of Insc to facilitate the asymmetric localisation and preferential segregation of Pon/Numb to the basal daughter destined to become RP2. Here we report that jumeaux (jumu), which encodes a new member of the winged-helix family of transcription factors, is required to mediate the asymmetric localisation and segregation of Pon/Numb but is dispensable for Insc apical localisation during the GMC4-2a cell division. In jumu mutants GMC4-2a Pon/Numb asymmetric localisation is defective and both daughter neurons can adopt the RP2 identity. Jumu protein shows nuclear localisation and within the NB4-2 lineage is first detected only after the first neuroblast cell division, in GMC4-2a. Our results suggest that in addition to the correct formation of an apical complex, transcription mediated by Jumu is also necessary to facilitate the correct asymmetric localisation and segregation of Pon/Numb.


Evidence for an anion exchange mechanism for uptake of conjugated bile acid from the rat jejunum.
Absorption of conjugated bile acids from the small intestine is very efficient. The mechanisms of jejunal absorption are not very well understood. The aim of this study was to clarify the mechanism of absorption of conjugated bile acid at the apical membrane of jejunal epithelial cells. Brush-border membrane vesicles from intestinal epithelial cells of the rat were prepared. Absorption of two taurine-conjugated bile acids that are representative of endogenous bile acids in many variate vertebrate species were studied. In ileal, but not jejunal brush-border membrane vesicles, transport of conjugated bile acids was cis-stimulated by sodium. Transport of conjugated bile acids was trans-stimulated by bicarbonate in the jejunum. Absorption of conjugated dihydroxy-bile acids was almost twice as fast as of trihydroxy-bile acids. Coincubation with other conjugated bile acids, bromosulfophthalein, and DIDS, as well as by incubation in the cold inhibited the transport rate effectively. Absorption of conjugated bile acids in the jejunum from the rat is driven by anion exchange and is most likely an antiport transport.


Oridonin induces apoptosis through the mitochondrial pathway in human gastric cancer SGC-7901 cells.
Oridonin is one of the most important antitumor active ingredients of Rabdosia rubescens. Recently published studies from our laboratory have demonstrated that oridonin was able to arrest human gastric cancer SGC-7901 cells at G2/M phase. However, little is known about inducing apoptosis in gastric cancer. The aim of this study was to investigate the effect of oridonin on antineoplastic capability of SGC-7901 cells and the detailed molecular mechanism of oridonin-mediated intrinsic pathway of apoptosis. Cell proliferation was assessed by MTT assay while apoptosis induced by oridonin was determined by Hoechst 33342 staining assay and Annexin V/PI double staining assay. Early apoptotic rate was stained by Annexin V/PI and detected by flow cytometry. Apoptosis pathway was analyzed by western blot analysis of Bcl-2, Bax, cytochrome c and caspase-3 expression. The results showed that oridonin was able to inhibit the SGC-7901 cell proliferation, the 50% growth inhibition (IC50) was 22.74 µM. Oridonin could induce cell apoptosis of SGC-7901 cells and the early apoptotic rates induced by 0, 20, 40, 80 µmol/l oridonin were 1.53±0.67, 3.33±0.29, 84.80±0.82 and 96.43±0.51%, respectively. Western blot analysis revealed that oridonin downregulated Bcl-2 protein (the anti-apoptotic factor) and upregulated Bax protein (pro-apoptotic factor), eventually leading to a reduction in the ratio of Bcl-2/Bax proteins. Furthermore, oridonin induced the release of cytochrome c from the mitochondria to the cytosol and the activation of caspase-3. Taken together, the current study suggested that oridonin induced apoptosis in SGC-7901 cells via the mitochondrial signal pathway, which may represent one of the major mechanisms of oridonin-mediated apoptosis in SGC-7901 cells.


Regulation of the Salmonella enterica std fimbrial operon by DNA adenine methylation, SeqA, and HdfR.
DNA adenine methylase (dam) mutants of Salmonella enterica serovar Typhimurium grown under laboratory conditions express the std fimbrial operon, which is tightly repressed in the wild type. Here, we show that uncontrolled production of Std fimbriae in S. enterica serovar Typhimurium dam mutants contributes to attenuation in mice, as indicated by the observation that an stdA dam strain is more competitive than a dam strain upon oral infection. Dam methylation appears to regulate std transcription, rather than std mRNA stability or turnover. A genetic screen for std regulators showed that the GATC-binding protein SeqA directly or indirectly represses std expression, while the poorly characterized yifA gene product serves as an std activator. YifA encodes a putative LysR-like protein and has been renamed HdfR, like its Escherichia coli homolog. Activation of std expression by HdfR is observed only in dam and seqA backgrounds. These data suggest that HdfR directly or indirectly activates std transcription. Since SeqA is unable to bind nonmethylated DNA, it is possible that std operon derepression in dam and seqA mutants may result from unconstrained HdfR-mediated activation of std transcription. Derepression of std in dam and seqA mutants of S. enterica occurs in only a fraction of the bacterial population, suggesting the occurrence of either bistable expression or phase variation.


Lay knowledge and management of malaria in Baringo county, Kenya.
Malaria, a disease caused by protozoan parasites of the genus Plasmodium and transmitted by female anopheline mosquitoes, is a major cause of morbidity, mortality and loss in productivity in humans. Baringo County is prone to seasonal transmissions of malaria mostly in the rainy seasons. This cross-sectional study used a mixed methods approach to collect data on knowledge and lay management of malaria. A questionnaire survey was administered to 560 respondents while qualitative data was collected through 20 focus group discussions in four ecological zones covering Baringo North, Baringo South and Marigat sub-Counties of Baringo County. Analyses were done through summary and inferential statistics for quantitative data and content analysis for qualitative data. The study communities were knowledgeable of malaria signs, symptoms, cause and seasonality but this biomedical knowledge co-existed with other local perceptions. This knowledge, however, did not influence their first (p = 0.77) or second choice treatments (p = 0.49) and compliance to medication (p = 0.84). Up to 88 % of respondents reported having suffered from malaria. At the onset of a suspected malaria case community members reported the following: 28.9 % visited a health facility, 37.2 % used analgesics, 26.6 % herbal treatments, 2.2 % remnant malaria medicines, 2.2 % over the counter malaria medicines, 1 % traditional healers and 1.8 % other treatments. Nearly all respondents (97.8 %) reported visiting a health facility for subsequent treatments. Herbal treatments comprised of infusions and decoctions derived from roots, barks and leaves of plants believed to have medicinal value. Compliance to conventional malaria treatment regime was, however, identified as a challenge in malaria management. Quick relief from symptoms, undesirable qualities like drug bitterness and bad smell, undesirable side-effects, such as nausea and long regimen of treatment were some of the contributors to non-compliance. Men and women exhibited different health-seeking behaviours based on the cultural expectations of masculinity, femininity, gender roles and acceptability of health services. While knowledge of malaria is important in identifying the disease, it does not necessarily lead to good management practice. Treatment-seeking behaviour is also influenced by perceived cause, severity of disease, timing, anticipated cost of seeking treatment and gender, besides the availability of both traditional and conventional medicines.


Precision of the Dpp gradient.
Morphogen concentration gradients provide positional information by activating target genes in a concentration-dependent manner. Recent reports show that the gradient of the syncytial morphogen Bicoid seems to provide precise positional information to determine target gene domains. For secreted morphogenetic ligands, the precision of the gradients, the signal transduction and the reliability of target gene expression domains have not been studied. Here we investigate these issues for the TGF-beta-type morphogen Dpp. We first studied theoretically how cell-to-cell variability in the source, the target tissue, or both, contribute to the variations of the gradient. Fluctuations in the source and target generate a local maximum of precision at a finite distance to the source. We then determined experimentally in the wing epithelium: (1) the precision of the Dpp concentration gradient; (2) the precision of the Dpp signaling activity profile; and (3) the precision of activation of the Dpp target gene spalt. As captured by our theoretical description, the Dpp gradient provides positional information with a maximal precision a few cells away from the source. This maximal precision corresponds to a positional uncertainly of about a single cell diameter. The precision of the Dpp gradient accounts for the precision of the spalt expression range, implying that Dpp can act as a morphogen to coarsely determine the expression pattern of target genes.


Total quality management in the health-care context: integrating the literature and directing future research.
Synergistic integration of predictors and elements that determine the success of total quality management (TQM) implementations in hospitals has been the bane of theoretical development in the TQM research area. Thus, this paper aims to offer a systematic literature review to provide a foundation on which research on TQM can be built and to identify the predictors of successful TQM in the health-care context. A systematic literature survey was adopted in this paper, involving the review of 25 relevant researched articles found in the databases Science Direct, EBSCO, MEDLINE, CINAHL and PubMed. The systematic literature survey reveals five variables to be core predictors of TQM, signifying how important these variables are in the successful implementation of TQM in the health-care context. Also, it is revealed that the identified core predictors have positive effects on an improved health-care system. However, the systematic survey of the literature reveals a dearth of studies on TQM in the health-care context. As TQM has become an important management approach for advancing effectiveness in the health-care sector, this kind of research is of value to researchers and managers. Stakeholders in the health sectors should introduce and implement TQM in hospitals and clinics. Nevertheless, this study has limitations, including that the databases and search engines adopted for the literature search are not exhaustive.


Seamless High-Q Microwave Cavities for Multimode Circuit Quantum Electrodynamics.
Multimode cavity quantum electrodynamics-where a two-level system interacts simultaneously with many cavity modes-provides a versatile framework for quantum information processing and quantum optics. Because of the combination of long coherence times and large interaction strengths, one of the leading experimental platforms for cavity QED involves coupling a superconducting circuit to a 3D microwave cavity. In this work, we realize a 3D multimode circuit QED system with single photon lifetimes of 2 ms across 9 modes of a novel seamless cavity. We demonstrate a variety of protocols for universal single-mode quantum control applicable across all cavity modes, using only a single drive line. We achieve this by developing a straightforward flute method for creating monolithic superconducting microwave cavities that reduces loss while simultaneously allowing control of the mode spectrum and mode-qubit interaction. We highlight the flexibility and ease of implementation of this technique by using it to fabricate a variety of 3D cavity geometries, providing a template for engineering multimode quantum systems with exceptionally low dissipation. This work is an important step towards realizing hardware efficient random access quantum memories and processors, and for exploring quantum many-body physics with photons.


The BET-bromodomain inhibitor JQ1 renders neuroblastoma cells more resistant to NK cell-mediated recognition and killing by downregulating ligands for NKG2D and DNAM-1 receptors.
Low expression of ligands for NK cell-activating receptors contributes to neuroblastoma (NB) aggressiveness. Recently, we demonstrated that the expression of MYCN, a poor prognosis marker in NB, inversely correlates with that of activating ligands. This indicates that MYCN expression level can predict the susceptibility of NB cells to NK cell-mediated immunotherapy and that its downregulation can be exploited as a novel therapeutic strategy to induce the expression of activating ligands. Here we evaluated the effect of the BET-bromodomain inhibitor JQ1 on the expression of ligands for NK cell-activating receptors in NB cell lines. Although downmodulating MYCN, JQ1 impaired the expression of ligands for NK cell-activating receptors, rendering NB cell lines more resistant to NK cell-mediated killing. The downregulation of activating ligands was due to JQ1-mediated impaired functions of both c-MYC and p53, two transcription factors known to regulate the expression of ULBP1-3 ligands for NKG2D activating receptor. Moreover JQ1 strongly downregulated the levels of ROS, a stress-induced signaling event associated with the induction of ligands for NK cell-activating receptors. These results suggest that the use of JQ1 should be discourage in combination with NK cell-based immunotherapy in a perspective chemotherapeutic treatment of NB. Thus, further investigations, exploiting molecular strategies aimed to boost the NK cell-mediated killing of NB cells, are warranted.


The carpometarcarpal ratio: a useful method for assessing disease progression in rheumatoid arthritis.
Determining the progression of anatomic involvement in rheumatoid arthritis (RA) is a well recognized problem. In 1976, Trentham and Masi described the carpometacarpal (CMC) ratio and found it useful for detecting progression of anatomic involvement in RA. Our study attempts to validate the efficacy of this ratio both in a cross sectional (n = 267) and longitudinal (n = 53) sample of patients with rheumatoid arthritis. Our data indicate that the CMC ratio is useful for quantitating anatomic involvement and correlates well with anatomic progression over time.


Prognosis of pancreatic cancer with Trousseau syndrome: a systematic review of case reports in Japanese literature.
Trousseau syndrome is a paraneoplastic syndrome associated with a risk of poor prognosis. We reviewed the survival time and prognosis of patients with Trousseau syndrome. We identified 40 cases from 28 reports of Trousseau syndrome due to pancreatic cancer. We analyzed 20 cases based on reports providing sufficient information on the stage/location of pancreatic cancer and survival time after Trousseau syndrome. The median survival time was 2.0 months. There was no statistical difference between performance status (PS) 0-1 and PS 4, stages I-III and IV, and pancreatic head and body/tail. However, statistically significant differences were noted between the median survival time of patients who continued treatment for pancreatic cancer even after Trousseau syndrome and those who discontinued treatment (P = 0.005). Although only a small number of cases were analyzed in this study, the results indicated that patients with pancreatic cancer who developed Trousseau syndrome had a poor prognosis, and chemotherapy should be continued, if possible.


[First Mexican Consensus of Vaccination in Adults].
For years our efforts have been focused on vaccination during childhood. Today we know that this is not enough to ensure health in the rest of the life. Childhood is as important as any other stage and, therefore, vaccination must be permanent and differentiated, according to our age, throughout life. Introducing a life course perspective in vaccination programs, with emphasis on adult vaccination, particularly in older adults, offers us the opportunity to review the performance of health programs, actions, and services in the field of immunization, as well as strengthening health promotion actions. In this context, the first Mexican Consensus on Adult Vaccination was carried out in a joint effort of the National Institute of Geriatrics, bringing together a group of specialists who worked on three central objectives: establishing vaccination guidelines throughout the life course, with emphasis on new vaccines; defining priority groups according to their risk factors; and contributing to the effort to promote healthy aging.


The Association between Indoor Air Quality and Adult Blood Pressure Levels in a High-Income Setting.
Background: Indoor air pollution is still considered one of the leading causes of morbidity and mortality worldwide. We aimed to investigate the potential association between indoor particulate matter (PM) and fasting clinic blood pressure in adult Australians. Methods: Sixty-three participants residing within the Perth metropolitan area were studied. Participants were aged between 18 and 65 years and free of major medical conditions. We conducted 24-h monitoring of residential PM concentrations, including the size fractions PM1, PM2.5, PM4, and PM10. All participants attended a clinical assessment at Curtin University following a 10⁻12 h overnight fast. Results: In this study we found that PM1 and PM2.5 were significantly associated with heart rate: a one interquartile range (IQR) increase in PM1 or PM2.5 was associated with a 4⁻6 beats per minute (bpm) increase in heart rate. Both PM10 and total PM exposure had a significant impact on systolic blood pressure (SBP): a one IQR increase in PM10 and total PM were associated with a 10 mmHg (95% CI: 0.77⁻20.05) and 12 mmHg (2.28⁻22.43 mmHg) increase in SBP, respectively. Conclusion: The study findings provide additional support to the thesis that indoor air pollution is an important modifiable factor in the risk of hypertension.


Comparative antiestrogenic activities of 2,3,7,8-tetrachlorodibenzo-p-dioxin and 6-methyl-1,3,8-trichlorodibenzofuran in the female rat.
The ED50s for the dose-response induction of hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the female Sprague-Dawley rat were 3.3 and 2.7 nmol/kg, respectively. In contrast, the corresponding ED50 values for induction by the nontoxic 6-methyl-1,3,8-trichlorodibenzofuran (MCDF) were 524 and 578 mumol/kg for AHH and EROD, respectively, and TCDD was greater than 1.5 X 10(5) more potent than MCDF as an agonist for this response. Cotreatment of the female rats with MCDF (20, 50, or 100 mumol/kg) and TCDD (6.4 nmol/kg) showed that MCDF partially antagonized the induction of AHH and EROD by TCDD and this corresponded with results previously reported in the male rat. Like TCDD, MCDF also caused a dose-response decrease in uterine and hepatic cytosolic and nuclear estrogen (ERc and ERn) and progesterone (PRc and PRn) receptor levels. The relative TCDD/MCDF potencies for the reduction of uterine ERc, ERn, PRc, and PRn levels were 293, 569, 560, and 459, respectively, and comparable potency ratios (693, 409, 405, and 424, respectively) were observed in the liver. Since MCDF was active as an antiestrogen at dose levels which caused only minimal induction of hepatic monooxygenases, it is unlikely that induction of these enzymes and the subsequent increased metabolism of estradiol play a role in the antiestrogenic effects of MCDF (or TCDD). The reasons for the differences in the relative potency of MCDF for the "traditional" Ah receptor-mediated response (i.e., AHH induction) and the modulation of steroid hormone receptor binding levels are unknown. MCDF, a compound which exhibits relatively high TCDD receptor binding activity and low toxicity, represents a new class of nontoxic halogenated aromatic antiestrogens that can be utilized to further probe the mechanism of this response in model systems.


[Diagnostic laparoscopy--a useful tool in abdominal lymphoma].
Imaging-guided (CT/US) percutaneous biopsy has significantly improved diagnosis of intra-abdominal lymphoma. However, in many cases the tissue retrieved may be inadequate for specialized studies such as immunophenotyping or cytogenetic analysis that may be required for a complete analysis of lymphoma or determination of therapy. The success of diagnostic laparoscopy in the diagnosis and staging of gastrointestinal malignancies suggests that it could be used for intra-abdominal lymphomas as well. We describe our experience in 15 patients with suspected lymphoma who underwent diagnostic laparoscopy during 1995-98. Preoperative investigation performed in all included percutaneous FNA in 9 without conclusive diagnosis. Laparoscopy was diagnostic for lymphoma in 14 (93%) while in 1 there was a false negative result due to sampling error and the lymphoma was only diagnosed at a second laparoscopy. There was no mortality nor any major complication. Average hospital stay was 2 days and patients were then referred for further oncological treatment. Our experience shows that diagnostic laparoscopy is a safe and efficient tool and without major complications in diagnosing abdominal lymphoma.


Xenograft rejection of porcine islet-like cell clusters in normal, interferon-gamma, and interferon-gamma receptor deficient mice.
The aim of the present study was to evaluate the role of the T-cell cytokine interferon (IFN)-gamma in mediating macrophage activation in xenograft rejection. For this purpose, fetal porcine islet-like cell cluster (ICC) transplants were placed under the renal capsule of normal mice and mice with a homozygous targeted disruption of the IFN-gamma or the IFN-gamma receptor gene. Some of the mice were continuously infused with cyclosporine (CsA, 12.4 mg/kg body weight/day) or CsA vehicle by subcutaneously implanted osmotic pumps. Histological evaluation of the xenografts was performed 6 or 12 days after transplantation. All animals, irrespective of recipient group, readily rejected the ICC xenograft, although the rejection process was slightly delayed in mice deficient in IFN-gamma. Analysis of the infiltrating cells within the xenograft in knockout mice revealed a pattern similar to that found in control animals. Six days after transplantation, there was an abundant infiltration of macrophages (Mac-1, F4/80, and major histocompatibility complex II markers) in the ICC grafts. Quite in contrast, there was only a low to moderate number of T cells (CD3 marker) present in the ICC grafts. Treatment with CsA had no effect on the rejection process. In grafts removed from mice with a disruption of the IFN-gamma gene, occasional surviving endocrine cells, and in some cases also a few intact ICC, were found within the otherwise obliterated xenograft. Few or no surviving endocrine cells were found in the grafts obtained from the other groups of mice. Thus, the present study demonstrates that macrophage activation, and subsequent destruction of an ICC xenograft, can operate in the absence of IFN-gamma in the pig-to-mouse model.


Expression of Cytokine Profiles in Human THP-1 Cells during Phase Transition of Talaromyces marneffei.
Talaromyces marneffei, a dimorphic fungus, exhibits temperature-dependent growth, existing in a filamentous form at 25 °C and as a yeast at 37 °C. Several studies have highlighted the important roles of macrophages in defense against T. marneffei infection. However, the immune responses to the interaction of macrophages with T. marneffei cells during phase transition require further investigation. This study reports the expression of cytokine profiles in human THP-1 cells during infection by T. marneffei. THP-1 cells were infected with T. marneffei conidia at different multiplicity of infections (MOIs). Surviving conidia transformed into yeasts after phagocytosis by macrophages, and the number of yeasts gradually increased over 36 h. The transcription and secretion levels of pro- and anti-inflammatory cytokines were examined at different times by qRT-PCR and ELISA. Transcription levels of IL-8, IL-12, IL-1β, and TNF-α increased significantly at 12 or 24 h and then slightly decreased at 36 h. In contrast, the transcription levels of IL-6, IL-10, and TGF-β gradually increased at all MOIs. The levels of IL-6 and IL-10 secretion corresponded to their levels of transcription. These results indicated that as the number of intracellular yeasts increased, the infected macrophages first underwent slight M1 polarization before shifting to M2 polarization. This polarization transition was confirmed by the fungicidal ability and the expression of macrophage surface markers. By inducing the M2-type polarization of macrophages, the intracellular T. marneffei cells can successfully evade the immune response. Our study provides a novel insight into the immune characterization during the transition of T. marneffei infection and could further contribute to possible diagnostic and therapeutic interventions for this infection.


Rapid signal enhancement method for nanoprobe-based biosensing.
The introduction of nanomaterials as detection reagents has enabled improved sensitivity and facilitated detection in a variety of bioanalytical assays. However, high nanoprobe densities are typically needed for colorimetric detection and to circumvent this limitation several enhancement protocols have been reported. Nevertheless, there is currently a lack of universal, enzyme-free and versatile methods that can be readily applied to existing as well as new biosensing strategies. The novel method presented here is shown to enhance the signal of gold nanoparticles enabling visual detection of a spot containing <10 nanoparticles. Detection of Protein G on paper arrays was improved by a 100-fold amplification factor in under five minutes of assay time, using IgG-labelled gold, silver, silica and iron oxide nanoprobes. Furthermore, we show that the presented protocol can be applied to a commercial allergen microarray assay, ImmunoCAP ISAC sIgE 112, attaining a good agreement with fluorescent detection when analysing human clinical samples.


Time-dependence of risperidone and asenapine sensitization and associated D2 receptor mechanism.
When an antipsychotic drug is given repeatedly and intermittently, there is often a long-term increase in its behavioral efficacy, termed antipsychotic sensitization. With the passage of time, the magnitude of antipsychotic sensitization may increase or decrease based on the principle of time-dependent sensitization (TDS) or memory decay, respectively. In the present study, we examined the time-dependent feature and possible dopamine D2 receptor mechanism of sensitization induced by risperidone and asenapine in the conditioned avoidance response test. Well-trained male adult Sprague-Dawley rats were first repeatedly treated with risperidone (1.0mg/kg) or asenapine (0.2mg/kg) and tested for avoidance response daily for 5 consecutive days. Eight, 18 or 38 days after the 5th drug treatment, all rats were retested drug-free to assess the long-term impact of prior risperidone or asenapine treatment. Drug-pretreated rats had significantly lower avoidance than vehicle-pretreated ones on this test, and the group differences increased with the passage of time. In the subsequent drug challenge test at 10, 20 or 40 days after the 5th drug treatment, all rats were injected with a low dose of risperidone (0.3mg/kg) or asenapine (0.1mg/kg). Drug-pretreated rats again made significantly fewer avoidances than controls, confirming the antipsychotic sensitization effect. Finally, in the quinpirole (a D2/3 receptor agonist, 1.0mg/kg, sc)-induced hyperlocomotion test, risperidone-pretreated rats exhibited a significantly higher level of motor activity than the vehicle-pretreated ones. These findings suggest that risperidone and asenapine sensitization is long-lasting, follows the TDS principle, and is likely mediated by D2 receptor supersensitivity.


Environmental ethics: an overview, assessing the place of bioscientists in society, supplemented with selected Australian perspectives.
Ethics deals with moral behavior in a professional context; ideally, it leads to a set of governing principles through which the appropriateness of any activity may be determined or assessed. Environmental ethics specifically deals with how humans interact with the biosphere. It is clear, however, that, as a species, we are failing in our duty of environmental stewardship. The encroachment of human activity into the natural environment is inexorable, and almost always deleterious. Any response to mitigate loss of taxa or ecosystems will have economic implications, and these are often considerable. In finding effective solutions, a process soon becomes political. In light of this we must reflect upon the leadership role that biologists have, especially our impact on policy development that pertains to natural resource management. Although our track record is no worse than any other professional group, biologists by way of training usually have a greater understanding of natural processes and must be prepared to articulate these publically. We have an ethical mandate to question decisions, policies and legislation that impact negatively upon biological systems: a mandate guided through logic, grounded in empirical science, and hopefully coupled with a deep understanding of the true value of both the living world and the physical world which sustains it. This paper uses Australian examples to demonstrate the frequent clashes between economics and biology, in anticipation that we should strive to achieve the underlying principles of sustainability, environmental stewardship and resource management in both daily decision-making and in long-term planning.


Antibacterial and antifungal activities of crude plant extracts from Colombian biodiversity.
On a global scale, people have used plants to treat diseases and infections, and this has raised interest on the plant biodiversity potencial in the search of antimicrobial principles. In this work, 75 crude n-hexanes, dichloromethane and methanol extracts from the aerial parts of 25 plants belonging to four botanical families (Asteraceae, Euphorbiaceae, Rubiaceae and Solanaceae), collected at the Natural Regional Park Ucumari (Risaralda, Colombia), were evaluated for their antibacterial and antifungal activities by the agar well diffusion method. The antibacterial activities were assayed against two Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis, and three Gram-negative ones named, Klebsiella pneumoniae, Escherichia coli and Pseudomonas aeruginosa. In addition, the same plant extracts were tested against the yeast Candida albicans and the fungi Aspergillus fumigatus and Fusarium solani. Overall, the plant extracts examined displayed better bactericide rather than fungicide activities. In general, the best antibacterial activity was showed by the plant extracts from the Rubiaceae family, followed in order by the extracts from the Euphorbiaceae and Solanaceae ones. It is important to emphasize the great activity displayed by the methanol extract of Alchornea coelophylla (Euphorbiaceae) that inhibited four out of five bacteria tested (B. Subtilis, P. aeruginosa, S. aureus and E. coli). Furthermore, the best Minimal Inhibitory Concentration for the extracts with antifungal activities were displayed by the dichloromethane extracts from Acalypha diversifolia and Euphorbia sp (Euphorbiaceae). The most susceptible fungus evaluated was F. Solani since 60% and 20% of the dichloromethane and methanol extracts evaluated inhibited the growth of this phytopathogenic fungus. The antimicrobial activity of the different plant extracts examined in this work could be related to the secondary metabolites contents and their interaction and susceptibility of pathogenic microorganism evaluated.


Tissue length modulates "stimulated actin polymerization," force augmentation, and the rate of swine carotid arterial contraction.
"Stimulated actin polymerization" has been proposed to be involved in force augmentation, in which prior submaximal activation of vascular smooth muscle increases the force of a subsequent maximal contraction by ∼15%. In this study, we altered stimulated actin polymerization by adjusting tissue length and then measured the effect on force augmentation. At optimal tissue length (1.0 L(o)), force augmentation was observed and was associated with increased prior stimulated actin polymerization, as evidenced by increased prior Y118 paxillin phosphorylation without changes in prior S3 cofilin or cross-bridge phosphorylation. Tissue length, per se, regulated Y118 paxillin, but not S3 cofilin, phosphorylation. At short tissue length (0.6 L(o)), force augmentation was observed and was associated with increased prior stimulated actin polymerization, as evidenced by reduced prior S3 cofilin phosphorylation without changes in Y118 paxillin or cross-bridge phosphorylation. At long tissue length (1.4 L(o)), force augmentation was not observed, and there were no prior changes in Y118 paxillin, S3 cofilin, or cross-bridge phosphorylation. There were no significant differences in the cross-bridge phosphorylation transients before and after the force augmentation protocol at all three lengths tested. Tissues contracted faster at longer tissue lengths; contractile rate correlated with prior Y118 paxillin phosphorylation. Total stress, per se, predicted Y118 paxillin phosphorylation. These data suggest that force augmentation is regulated by stimulated actin polymerization and that stimulated actin polymerization is regulated by total arterial stress. We suggest that K(+) depolarization first leads to cross-bridge phosphorylation and contraction, and the contraction-induced increase in mechanical strain increases Y118 paxillin phosphorylation, leading to stimulated actin polymerization, which further increases force, i.e., force augmentation and, possibly, latch.


Epigenetic regulation of protein-coding and microRNA genes by the Gfi1-interacting tumor suppressor PRDM5.
Gfi1 transcriptionally governs hematopoiesis, and its mutations produce neutropenia. In an effort to identify Gfi1-interacting proteins and also to generate new candidate genes causing neutropenia, we performed a yeast two-hybrid screen with Gfi1. Among other Gfi1-interacting proteins, we identified a previously uncharacterized member of the PR domain-containing family of tumor suppressors, PRDM5. PRDM5 has 16 zinc fingers, and we show that it acts as a sequence-specific, DNA binding transcription factor that targets hematopoiesis-associated protein-coding and microRNA genes, including many that are also targets of Gfi1. PRDM5 epigenetically regulates transcription similarly to Gfi1: it recruits the histone methyltransferase G9a and class I histone deacetylases to its target gene promoters and demonstrates repressor activity on synthetic reporters; on endogenous target genes, however, it functions as an activator, in addition to a repressor. Interestingly, genes that PRDM5 activates, as opposed to those it represses, are also targets of Gfi1, suggesting a competitive mechanism through which two repressors could cooperate in order to become transcriptional activators. In neutropenic patients, we identified PRDM5 protein sequence variants perturbing transcriptional function, suggesting a potentially important role in hematopoiesis.


Dynamic mitochondrial-nuclear redistribution of the immunophilin FKBP51 is regulated by the PKA signaling pathway to control gene expression during adipocyte differentiation.
Glucocorticoids play an important role in adipogenesis through the glucocorticoid receptor (GR) that forms a heterocomplex with Hsp90•Hsp70 and one high molecular weight immunophilin, either FKBP51 or FKBP52. When 3T3-L1 preadipocytes are induced to differentiate, FKBP51 expression progressively increases, whereas FKBP52 decreases, and Hsp90, Hsp70, p23 and Cyp40 remain unchanged. Interestingly, FKBP51 rapidly translocates from mitochondria to the nucleus where it is retained upon its interaction with chromatin and the nuclear matrix. FKBP51 nuclear localization is transient, and after 48 hours it cycles back to mitochondria. Importantly, this dynamic FKBP51 mitochondrial-nuclear shuttling depends on PKA signaling, because its inhibition by PKI or knockdown of PKA-cα by siRNA, prevented FKBP51 nuclear translocation induced by IBMX. In addition, the electrophoretic pattern of migration of FKBP51 is altered by treatment of cells with PKI or knockdown of PKA-cα, suggesting that FKBP51 is a PKA substrate. In preadipocytes, FKBP51 colocalizes with PKA-cα in mitochondria. When adipogenesis is triggered, PKA-cα also moves to the nucleus colocalizing with FKBP51 mainly in the nuclear lamina. Moreover, FKBP51 and GR interaction increases when preadipocytes are induced to differentiate. GR transcriptional capacity is reduced when cells are incubated in the presence of IBMX, forskolin or dibutyryl-cAMP, compounds that induced FKBP51 nuclear translocation, but not by a specific activator of EPAC. FKBP51 knockdown facilitates adipogenesis, whereas ectopic expression of FKBP51 blocks adipogenesis. These findings indicate that the dynamic mitochondrial-nuclear shuttling of FKBP51 regulated by PKA may be key in fine-tuning the transcriptional control of GR target genes required for the acquisition of adipocyte phenotype.


Role of epidermal growth factor in gastroduodenal mucosal protection.
Epidermal growth factor (EGF) is a polypeptide produced in the submandibular glands, Brunner's glands, and the kidneys. The peptide is secreted in an exocrine fashion into saliva, duodenal juice, and urine. EGF stimulates cellular growth and differentiation and inhibits gastric acid secretion. Removal of the submandibular glands decreases the amount of EGF in saliva and gastric juice and subsequently the synthesis of DNA in the gastric mucosa is reduced as well as its resistance to bile-salt-induced gastric lesions. Intragastric instillation of EGF can prevent gastric ulcerations induced by aspirin as well as cysteamine in rats. EGF also accelerates the healing of chronic gastric ulcers induced by acetic acid. Cysteamine is a duodenal ulcerogen in rats. After cysteamine administration, the secretion of EGF from Brunner's glands decreases and the glands become depleted of mucus. Intraduodenal instillation of EGF can partly prevent formation of cysteamine-induced duodenal ulcers. Oral administration of EGF can accelerate healing of chronic duodenal ulcers in rats. The beneficial effect of EGF on healing of chronic gastroduodenal ulcers is probably due to the delayed effects of EGF such as stimulation of RNA and DNA synthesis. The protective effects of EGF are probably related to the early actions of the peptide such as activation of cell surface proteins and increased glycosaminoglycan synthesis.


Ascertaining the epidemiology, patient flow and disease management for Dravet syndrome in Spain.
Dravet syndrome (DS) is a rare, drug resistant epilepsy that starts very early in life with febrile seizures followed by cognitive impairment and diverse seizure types. To generate evidence on the epidemiology of DS, its diagnosis, patient-flow, treatment and unmet needs from the perspective of Spanish experts. A two-round Delphi study involving 19 physicians was conducted. Questionnaires were based on literature review and validated by clinical experts. Consensus was reached when topics were subject to routine clinical practice and individual experience, or the coefficient of variation among answers was <= 0.3. The estimated number of new DS patients is 73 per year. Prevalence is estimated to be between 348-540 patients. DS is mostly diagnosed in children. Survival varies from 5 to 60 years. There is no standardised follow-up of patients beyond the age of 18 and mortality rates are uncertain. No standard guidelines exist for diagnosing or treating DS. It takes 9 to 15 months to confirm the diagnosis and genetic testing is unevenly available. Valproic acid, clobazam, stiripentol and topiramate are commonly used. Poor efficacy and safety are the main reasons for treatment switch. The epidemiology of DS in Spain is not well known and several areas of unmet needs still exist. Experts' views offer a starting point for further research into the reality of DS in Spain. Epidemiological studies, consensus criteria, easy access to genetic testing, treatment options, training and research into quality of life aspects are highly needed.


Regulation of chondrocyte biosynthetic activity by dynamic hydrostatic pressure: the role of TRP channels.
Chondrocytes perceive and respond to mechanical loading as signals that regulate their metabolism. Joint loading exposes chondrocytes to multiple modes of mechanical stress, including hydrostatic pressure; however, the mechanisms by which chondrocytes sense physiologically relevant levels of hydrostatic pressure are not well understood. We hypothesized that hydrostatic pressure is transduced to an intracellular signal through mechanosensitive membrane ion channels of chondrocytes. The goals of this study were to examine the effect of hydrostatic loading on the development of engineered cartilage tissue and the contribution of mechanosensitive ion channels on these hydrostatic loading effects. Using a 3D model of porcine chondrocytes in agarose, we applied specific chemical inhibitors to determine the role of transient receptor potential (TRP) ion channels TRPV1, TRPV4, TRPC3, and TRPC1 in transducing hydrostatic pressure. Hydrostatic loading caused a frequency and magnitude-dependent decrease in sulfated glycosaminoglycans (S-GAG), without changes in DNA content. Inhibiting TRPC3 and TRPV4 decreased S-GAG content; however, only the inhibition of TRPV1 partially attenuated the hydrostatic loading-induced reduction in S-GAG content. Our findings indicate that TRPV1 may serve as a transducer of hydrostatic pressure in chondrocytes, and provide further support for the role of TRPV4 in regulating chondrocyte anabolism, as well as initial evidence implicating TRPC3 in chondrogenesis. These findings add to our further understanding of the chondrocyte "channelome" and suggest that a range of ion channels mediate the transduction of different biophysical stimuli such as hydrostatic pressure, membrane stretch, or osmotic stress.


How do cardiovascular risk prediction equations developed among 30-74 year olds perform in older age groups? A validation study in 125 000 people aged 75-89 years.
Cardiovascular disease (CVD) risk prediction equations are being used to guide risk management among increasingly older individuals. We examined the performance of recent equations, derived from a 2006 cohort including almost all New Zealanders aged 30-74 years, among older people. All New Zealanders aged 75-89 years in contact with state-funded health services in 2006 without prior CVD or heart failure and with complete predictor data were identified by anonymised individual-level linkage of eight national administrative health datasets. Baseline 5-year CVD risk was estimated using sex-specific New Zealand risk equations, and CVD hospitalisations or deaths occurring between 2007 and 2011 inclusive were ascertained. Performance was assessed with calibration plots and standard metrics. Among 124 358 New Zealanders aged 75-89 years old, 30 152 CVD events were recorded during follow-up. Sex-specific equations derived from 30-74 year olds slightly underestimated CVD risk among women and slightly overestimated risk among men aged 75-89 years. Discrimination metrics were poor in both sexes and the risk equations explained only 9.4% of the variation in time to CVD event among women and 6.0% for men. In the 5-year age bands, progressively worsening underprediction in women, overprediction in men and poorer performance metrics were observed with increasing age. Entire-population CVD risk equations developed among 30-74 year olds do not perform well among older people. Existing risk algorithms developed from primarily middle-aged or early-retirement cohorts should be used with caution in those aged ≥75 years until carefully validated in narrow age bands to avoid masking poorer performance in older age groups.


More than 10 years' continuous oral treatment with specific immunoglobulin Y for the prevention of Pseudomonas aeruginosa infections: a case report.
Immunotherapy with specific antibodies is an alternative to antibiotics for the prevention of infections in humans and animals. We have used orally administered immunoglobulin Y (IgY) preparations, purified from eggs of hens immunized with Pseudomonas aeruginosa bacteria, to prevent pulmonary P. aeruginosa infections in a group of patients with cystic fibrosis (CF). Respiratory infections are major problems for CF patients because of the thick mucus in the airways, and chronic P. aeruginosa lung infections occur in virtually all CF patients and cause morbidity and mortality. The IgY-treated group had only 2.5 P. aeruginosa-positive sputum cultures per 100 months, and none of the IgY-treated patients became chronically colonized with P. aeruginosa. In the control group, 13.7 of the cultures per 100 months were positive for P. aeruginosa, and 24% of patients became chronically colonized with P. aeruginosa. The first enrolled patient in this study has now been treated continuously for more than 10 years. During the first 8 years she only had four P. aeruginosa-positive cultures. After 8 years she became chronically infected, but still after 10 years the bacteria have not turned mucoid. No negative side effects of IgY treatment have been noted during these 10 years. To our knowledge this is the longest treatment with specific yolk antibodies for therapeutic purposes.


Effects on Gambling Activity From Coronavirus Disease 2019-An Analysis of Revenue-Based Taxation of Online- and Land-Based Gambling Operators During the Pandemic.
Background: Concerns have been raised about increased gambling problems during the coronavirus disease (COVID-19) crisis, particularly in settings with high online gambling and risks of migration from land-based to riskier online-based gambling types. However, few non-self-reported data sources are hitherto available. The present study aimed to assess changes in the online- and land-based gambling markets in Sweden during the first months affected by the societal impact of COVID-19. Methods: Data were derived from national authority data describing monthly taxations of all licensed Swedish gambling operators, whose monthly tax payments are directly based on gambling revenue. Subdivisions of the gambling market were followed monthly from before COVID-19 onset in Sweden (mainly February 2020) through June 2020, when the sports market was restarted after COVID-19 lockdown. Results: Overall revenue-based taxations in the licensed gambling decreased markedly from February to March, but stabilized onto an overall modest decrease through June. Commercial online casino/betting, despite some decrease in March, was maintained on a relatively stable level through June. However, within this category, horse betting increased steeply during the pandemic but returned to prepandemic levels later during the period. The state-owned operator in betting/online casino decreased markedly throughout the pandemic. The remaining commercial operators, mainly in online casino and online betting, demonstrated no change during the pandemic and ended on a June level 14% above the February level. Throughout the pandemic, the smaller restaurant casinos decreased markedly, while major state-owned casinos also closed entirely. State-owned lotteries and electronic gambling machines decreased markedly but were rapidly normalized to prepandemic levels. Conclusions: Commercial online gambling operators' revenues remained stable throughout the pandemic, despite the dramatic lockdown in sports. Thus, chance-based online games may have remained a strong actor in the gambling market despite the COVID-19 crisis, in line with previous self-report data. A sudden increase in horse betting during the sports lockdown and its decrease when sports reopened confirm the picture of possible COVID-19-related migration between gambling types, indicating a volatility with potential impact on gambling-related public health.


Forest age estimation in northern Arkhangelsk region based on machine learning pipeline on Sentinel-2 and auxiliary data.
Tree age is one of the key characteristics of a forest, along with tree species and height. It affects management decisions of forest owners and allows researchers to analyze environmental characteristics in support of sustainable development. Although forest age is of primary significance, it can be unknown for remote areas and large territories. Currently, remote sensing (RS) data supports rapid information gathering for wide territories. To automate RS data processing and estimate forest characteristics, machine learning (ML) approaches are applied. Although there are different data sources that can be used as features in ML models, there is no unified strategy on how to prepare a dataset and define a training task to estimate forest age. Therefore, in this work, we aim to conduct a comprehensive study on forest age estimation using remote sensing observations of the Sentinel-2 satellite and two ML-based approaches for forestry inventory data, namely stand-based and pixel-based. We chose the CatBoost algorithm to assess these two approaches. To establish the robustness of the pipeline, an in-depth analysis is conducted, embracing diverse scenarios incorporating dominant species information, tree height, Digital Elevation Model (DEM), and vegetation indices. We performed experiments on forests in the northern Arkhangelsk region and obtained the best Mean Absolute Error (MAE) result of 7 years in the case of the stand-based approach and 6 years in the case of the pixel-based approach. These results are achieved for all available input data such as spectral satellites bands, vegetation indices, and auxiliary forest characteristics (dominant species and height). However, when only spectral bands are used, the MAE metric is the same both for per-pixel and per-stand approaches and equals 11 years. It was also shown that, despite high correlation between forest age and height, only height can not be used for accurate age estimation: the MAE increases to 18 and 26 years for per-pixel and per-stand approaches, respectively. The conducted study might be useful for further investigation of forest ecosystems through remote sensing observations.


Bluetongue virus serotype 8: abortion and transplacental transmission in cattle in the Burgundy region, France, 2008-2009.
During the incursion of bluetongue virus (BTV) serotype 8 in France in 2007, an increase in the number of abortions in cattle was observed, but the cause was not clearly established. A survey of all the reported cases of abortion in cattle from November 2008 to April 2009 was conducted in the Nièvre district (Burgundy region) to determine the percentage of abortions as a result of BTV-8 and to study factors that could have played a role in BTV-8 transplacental transmission. BTV-8 was present in 16% of the fetuses or newborn calves that died within 48 h, from 780 dams. Dams inseminated before the BTV epizootic peak recorded from July to September 2008 were more likely to have BTV-positive abortions (OR=5.7, P<0.001) and those vaccinated in May or June 2008 were less likely to have BTV-positive abortions (OR=0.3, P=0.01 and OR=0.4, P=0.001, respectively). The gestational month was not a predictor of BTV abortion. In blood or spleen, fetuses/calves from RT-PCR-positive dams had significantly higher RNA concentrations than fetuses/calves from RT-PCR-negative dams. Of the 128 dams that had BTV-positive fetuses or calves, 60% were RT-PCR-negative. BTV-8-positive fetuses/calves were significantly more frequent (n=42 vs n=21, P=0.082) amongst those showing clinical signs or lesions suggestive of cerebral damage.


[Effective tracing of osteoporosis at a fracture and osteoporosis clinic in Groningen; an analysis of the first 100 patients].
To analyse the results from a fracture and osteoporosis (FO) outpatient clinic in order to achieve efficient case-finding for osteoporosis in patients of 50 years and older with a fracture due to low-energy trauma. Descriptive. Following the publication of new professional guidelines for case-finding and treatment of osteoporosis, an FO outpatient clinic was opened at the University Hospital of Groningen, The Netherlands, to which patients of 50 years and older with a fracture due to low-energy trauma could be referred for further diagnosis and treatment after initial treatment for trauma. Bone-mineral density of the lumbar spine, hip and distal radius was assessed with dual-energy X-ray absorptiometry (DEXA). Patients with manifest osteoporosis, defined as having a fracture and a T-score < or = -2 SD at one of the measured sites, were put on medication. The results from the first 100 patients were analysed. In the first five months 74% (116/156) of the patients were seen in the FO clinic. In January 2004 the first 100 patients completed the diagnostic process. A total of 67 patients had manifest osteoporosis, 20 osteopenia and 13 had normal bone density. Furthermore, 48% of the patients between 50 and 60 years old had manifest osteoporosis. Unrecognised vertebral fractures were found in 21 patients. Forty-three percent of patients with manifest osteoporosis had low 25-OH-vitamine D levels (< 30 nmol/l). Eleven patients were sent to the Department of Internal Medicine on indication of secondary osteoporosis. The FO outpatient clinic proved to be effective and useful for identifying and treating a population at risk of osteoporosis.