Nanostructured tungsten sulfides: insights into precursor decomposition and the microstructure using X-ray scattering methods.
Herein we present an in-depth study of precursor derived tungsten sulfides, with a focus on their micro- and local structures. We prepared a new tetrathiotungstate based precursor (N2H5)2WS4 and unveiled the details of its unique decomposition mechanism by a combination of in situ and ex situ analytical techniques. Upon heating the precursor, a new compound with composition (NH4)(N2H5)WS4 is formed by the decomposition of one hydrazinium molecule. Above ∼190 °C, (NH4)2WS4 crystallized as the second crystalline intermediate followed by successive decomposition to WS2via amorphous WS3 upon increasing the temperature. Using X-ray diffraction, total scattering data and pair distribution function (PDF) analyses we are able to develop a detailed picture of the microstructure of nanosized WS2 samples obtained by the thermal decomposition of the precursor. The microstructure is described by global optimization of the stacking pattern of WS2 slabs in a supercell containing a large number of layers. The results clearly demonstrate that both stacking faults and random shifts of the WS2 layers contribute to the disorder in the material. This is significantly distinct to bulk materials, where solely stacking faults with no turbostratic disorder components were found.


The response of parotid hemangiomas to the use of systemic interferon alfa-2a or corticosteroids.
To evaluate medical treatment for hemangiomas involving the parotid area with or without other areas of involvement. Retrospective analysis of pediatric patients treated medically for proliferative hemangiomas of the parotid region with or without hemangiomas in other regions. Indications for treatment included respiratory symptoms relating to hemangiomas of the upper airway, difficulty feeding, rapid rate of growth of the hemangioma, and deformity or obstruction of the ear canal. New York University Multidisciplinary Vascular Anomaly Conference, New York, NY, and the Pediatric Oncology Department of Ospedale Pediatrico Bambino Gesu, Rome, Italy. Thirteen patients with proliferative hemangiomas in the parotid area were treated medically to inhibit growth and enhance involution of the hemangioma. Six patients were treated with corticosteroids alone (2-4 mg/kg daily). Two patients were treated with corticosteroids (2-4 mg/kg daily) followed by interferon alfa-2a (3 million U/m2 daily) because of a failure to respond to corticosteroid therapy. One patient was treated with interferon alfa-2a alone (3 million U/m2 daily). Four patients were initially treated with interferon alfa-2a, then treated with corticosteroids. One of these patients required intralesional corticosteroid therapy for a massively enlarged lip and is therefore included in this group. The other patient was given oral corticosteroids for unknown reasons at another institution. In the remaining 2 patients, there was no response to the use of interferon alfa-2a. The size, bulk, and symptoms relating to the hemangiomas of the patients were assessed. None of the patients had a significant improvement of the lesions of the parotid hemangiomas. In contrast, for those patients with clinical symptoms due to hemangiomas elsewhere or with cutaneous involvement typical of hemangiomas, the symptoms improved with either of the above therapies, and the cutaneous areas demonstrated signs of involution. The results in the 13 patients in this article demonstrate that hemangiomas in certain anatomic sites, such as the parotid area, may be more resistant to therapy with corticosteroids or interferon alfa-2a. Differences in drug metabolism, caliber of blood vessels, and/or blood flow in the parotid gland may account for this observation.


Calcitonin gene-related peptide, substance P, nitric oxide and epinephrine modulate bone marrow micro circulation of the rabbit tibia and femur.
Different bones have different blood supplies, which may influence bone healing. Therefore, elucidation of the mechanisms involved in the regulation of bone marrow blood flow in different bones is of high clinical importance. To assess the micro circulation of bone marrow of the femur and tibia simultaneously, flow velocities were continuously measured by a two-channel laser-Doppler flowmeter. The probes were introduced into the femoral and tibial diaphysis, respectively, in the anesthetized rabbit. Changes in micro circulation of the bone marrow were elicited by intra-arterial bolus injections of vasoactive substances: epinephrine (E), calcitonine-gene related peptide (CGRP), substance P (SP), sodium nitroprusside (SNP), E and Ebrantil. Systemic arterial blood pressure was recorded with an electro-manometer. Micro vascular resistance (MVR) and 50% recovery time (50RT) to baseline flow level were calculated from the measured data. Flow velocity in the femur was significantly higher. Epinephrine considerably reduced micro vascular blood flow, which could be significantly warded off by Ebrantil. CGRP and SP did not change MVR. Application of SNP resulted in reduction of flow velocity, but it also decreased MVR. No statistically significant differences were found between reactions of the micro circulation in the two marrows. These results suggest that there are no significant differences between the blood flow response patterns of these two bone marrow sites, thus the regulation patterns of the micro circulation of the two bones are also similar.


Reprint of "Deficits of hot executive function in developmental coordination disorder: Sensitivity to positive social cues".
Recent research shows that children with motor coordination problems (or developmental coordination disorder--DCD) show deficits in not only cool executive function (EF), but also hot EF. We aimed to determine whether this deficit of hot EF is due to heightened sensitivity to rewarding stimuli, specifically, or to a general deficit of cognitive control, like inhibition. Using two versions of a go/no-go task, one with neutral facial expressions and the other with happy and fearful faces, we compared 12 children with DCD with 28 typically-developing children, aged 7-12 years. Like earlier studies, children responded faster to happy faces. Both groups showed comparable accuracy in response to go targets, and also had similar commission errors, except when the no-go stimulus was a happy face. Importantly, the DCD group made significantly more commission errors to happy faces failing to suppress their response on more than half of the no-go trials. These results suggest a heightened sensitivity to emotionally significant distractors in DCD; this type of impulsivity may undermine self-regulation in DCD, with possible implications for adaptive function and emotional well-being. We argue that the interaction of cognitive control and emotion processing networks may be disrupted in DCD or delayed in development.


Spectroscopic evidence for the uneven distribution of adenine and uracil residues in ribosomal ribonucleic acid of Drosophila melanogaster and of Plasmodium knowlesi and its possible evolutionary significance.
RNA was isolated from subribosomal particles of the malaria parasite Plasmodium knowlesi. The nucleotide composition (mole fraction) of the principal species was obtained (S-rRNA, 0.295A, 0.36U, 0.25G, 0.105C: L-rRNA, 0.326A, 0.31U, 0.228G, 0.144C). Ribosomal RNA was also isolated from Drosophila melanogaster. Optical properties of these A + U-rich species were measured. In all four cases analysis of the hypochromic effect revealed that adenine and uracil residues tended to form clusters along the polynucleotide chain. A substantial fraction of residues was located in bihelical regions of approx. 50% G-C base pairs or in regions of approx. 30-35% G-C base pairs. The possible evolutionary significance of these results was considered on the basis of comparison with properties of rRNA from bacteria (Escherichia coli) and a mammal (rabbit reticulocyte).


Corn? When did I eat corn? Gastrointestinal transit time in health science students.
The objective of this study was to determine gastrointestinal transit time in first-year health science students with a laboratory practical exercise conducted in two cohorts (classes of 2018 and 2019) of first-year health sciences students at the Health Science Campus in Windhoek, Namibia. All first-year health science students undertaking the Physiology course were invited to take part in the laboratory exercise. The primary outcome was the measurement of gastrointestinal transit time from the amount of time taken for ingested whole-kernel sweetcorn to be eliminated, which was calculated as the time period between ingestion of corn and the time of corn first seen in the stool and the time corn was last seen in the stool. The secondary outcome was an association between emotional irritability and/or anxiety and gastrointestinal transit time. The study analyzed responses of 175 students, who reported a median transit time of 29 (1-99) h. There was no difference in gastrointestinal transit time between male and female students. Likewise, there was no difference in the duration of the corn in the bowel between male and female students. Students who reported being worried and irritable during the exercise had more bowel movements before they saw corn in their stool and had slower transit times, respectively. A wider range of transit time was reported in a group of young, healthy students compared with previous studies in the literature. There were no differences between male and female student bowel activity. Anxiety did impact the bowel activity of the participants.


[On work conditions and occupational morbidity in Permsky area].
Permsky area is one of the most developed regions in Russia and among national industrial leaders. Registered level of occupational diseases in Permsky area does not correspond to work conditions state in industry. Over last 10 years, more than third of workers started having hazardous work conditions, number of the workers reduced more than by 200,000. Small-scale and medium business employers do not pay proper attention to health care for workers, and the situation concerning occupational hygiene in these enterprises deteriorates. Workers' health care is topical problem for Permsky area, necessitates systemic and complex actions within federal and regional goal-oriented program.


Collaborative peer review process as an informal interprofessional learning tool: Findings from an exploratory study.
Despite numerous studies on formal interprofessional education programes, less attention has been focused on informal interprofessional learning opportunities. To provide such an opportunity, a collaborative peer review process (CPRP) was created as part of a peer-reviewed journal. Replacing the traditional peer review process wherein two or more reviewers review the manuscript separately, the CPRP brings together students from different professions to collaboratively review a manuscript. The aim of this study was to assess whether the CPRP can be used as an informal interprofessional learning tool using an exploratory qualitative approach. Eight students from Counselling Psychology, Occupational and Physical Therapy, Nursing, and Rehabilitation Sciences were invited to participate in interprofessional focus groups. Data were analysed inductively using thematic analysis. Two key themes emerged, revealing that the CPRP created new opportunities for interprofessional learning and gave practice in negotiating feedback. The results reveal that the CPRP has the potential to be a valuable interprofessional learning tool that can also enhance reviewing and constructive feedback skills.


Improving efficacy of diabetes management using treatment algorithms in a mainly Hispanic population.
To compare clinical outcomes obtained using treatment algorithms versus standard "usual care" to treat patients with type 2 diabetes in a community setting. An observational group comparison was implemented in three community-based clinics in San Antonio, Texas: 1). a community clinic following treatment algorithms (CC-TA), 2). university clinic following treatment algorithms (UC-TA), and 3). a community clinic following standard "usual care" practices (CC-SC). Three hundred fifty-eight recently diagnosed type 2 diabetic patients (90% Mexican American, from low-income neighborhoods) who were consecutively identified at the three clinics were recruited. Following medical and laboratory evaluation, participants were started on treatment for hyperglycemia, hypertension, and dyslipidemia and followed for 12 months. Decrements in HbA(1c) at 12 months in the CC-TA and UC-TA were 3.1 and 3.3%, respectively, compared to 1.3% in the CC-SC (P < 0.0001). Corresponding decrements in fasting plasma glucose at 12 months were 94 and 99 mg/dl, respectively, versus 38 mg/dl in CC-SC (P < 0.0001). Reductions in total cholesterol, LDL cholesterol, and triglycerides at 12 months were greater in both algorithm-managed clinics compared to standard care-managed clinics (P < 0.0001). In algorithm-managed clinics, there were 30% more documented eye exams and 24% more documented foot exams than in standard care-managed patients. Adherence to the treatment algorithms improved metabolic outcomes in type 2 diabetic patients to a greater extent than standard care practices. These results have important clinical implications for the treatment of type 2 diabetic patients.


Comparative analysis of the bovine MHC class IIb sequence identifies inversion breakpoints and three unexpected genes.
The bovine major histocompatibility complex (MHC) or BoLA is organized differently from typical mammalian MHCs in that a large portion of the class II region, called class IIb, has been transposed to a position near the centromere on bovine chromosome 23. Gene mapping indicated that the rearrangement resulted from a single inversion, but the boundaries and gene content of the inverted segment have not been fully determined. Here, we report the genomic sequence of BoLA IIb. Comparative sequence analysis with the human MHC revealed that the proximal inversion breakpoint occurred approximately 2.5 kb from the 3' end of the glutamate-cysteine ligase, catalytic subunit (GCLC) locus and that the distal breakpoint occurred about 2 kb from the 5' end from a divergent class IIDRbeta-like sequence designated DSB. Gene content, order and orientation of BoLA IIb are consistent with the single inversion hypothesis when compared with the corresponding region of the human class II MHC (HLA class II). Differences with HLA include the presence of a single histone H2B gene located between the proteasome subunit, beta type, 9 (PSMB9) and DMB loci and a duplicated TAP2 with a variant splice site. BoLA IIb spans approximately 450 kb DNA, with 20 apparently intact genes and no obvious pseudogenes. The region contains 227 simple sequence repeats (SSRs) and approximately 167 kb of retroviral-related repetitive DNA. Nineteen of the 20 genes identified in silico are supported by bovine EST data indicating that the functional gene content of BoLA IIb has not been diminished because it has been transposed from the remainder of BoLA genes.


In vitro adenosine triphosphate based chemotherapy response assay in gastric cancer.
The purpose of this study was to investigate the reliability and the clinical applicability of the adenosine-triphosphate-based chemotherapy response assay (ATP-CRA) as a method of determining in vitro chemosensitivity in patients with gastric cancer. A total of 243 gastric cancer tissue samples were obtained from gastrectomies performed between February 2007 and January 2010. We evaluated the effectiveness of the ATP-CRA assay in determining the chemosensitivity of gastric cancer specimens using eleven chemotherapeutic agents - etoposide, doxorubicin, epirubicin, mytomicin, 5-fluorouracil, oxaliplatin, irinotecan, docetaxel, paclitaxel, methotraxate, and cisplatin - for chemosensitivity studies using ATP-CRA. We assessed the failure rate, the cell death rate, and the chemosensitivity index. The failure rate of ATP-CRA was 1.6% (4/243). The mean coefficient of variation for triplicate ATP measurements was 6.5%. Etoposide showed the highest cell death rate (35.9%) while methotrexate showed the lowest (16.6%). The most active chemotherapeutic agent was etoposide, which most frequently ranked highest in the chemosensitivity test: 31.9% (51/160). Oxaliplatin was more active against early gastric cancers than advanced gastric cancers, whereas docetaxel was more active against advanced cancers. The lymph node negative group showed a significantly higher cell death rate than the lymph node positive group when treated with doxorubicin, epirubicin, and mitomycin. ATP-CRA is a stable and clinically applicable in vitro chemosensitivity test with a low failure rate. The clinical usefulness of ATP-CRA should be evaluated by prospective studies comparing the regimen guided by ATP-CRA with an empirical regimen.


DNA Minicircle Technology Improves Purity of Adeno-associated Viral Vector Preparations.
Adeno-associated viral (AAV) vectors are considered as one of the most promising delivery systems in human gene therapy. In addition, AAV vectors are frequently applied tools in preclinical and basic research. Despite this success, manufacturing pure AAV vector preparations remains a difficult task. While empty capsids can be removed from vector preparations owing to their lower density, state-of-the-art purification strategies as of yet failed to remove antibiotic resistance genes or other plasmid backbone sequences. Here, we report the development of minicircle (MC) constructs to replace AAV vector and helper plasmids for production of both, single-stranded (ss) and self-complementary (sc) AAV vectors. As bacterial backbone sequences are removed during MC production, encapsidation of prokaryotic plasmid backbone sequences is avoided. This is of particular importance for scAAV vector preparations, which contained an unproportionally high amount of plasmid backbone sequences (up to 26.1% versus up to 2.9% (ssAAV)). Replacing standard packaging plasmids by MC constructs not only allowed to reduce these contaminations below quantification limit, but in addition improved transduction efficiencies of scAAV preparations up to 30-fold. Thus, MC technology offers an easy to implement modification of standard AAV packaging protocols that significantly improves the quality of AAV vector preparations.


Protecting Physical Layer Secret Key Generation from Active Attacks.
Lightweight session key agreement schemes are expected to play a central role in building Internet of things (IoT) security in sixth-generation (6G) networks. A well-established approach deriving from the physical layer is a secret key generation (SKG) from shared randomness (in the form of wireless fading coefficients). However, although practical, SKG schemes have been shown to be vulnerable to active attacks over the initial "advantage distillation" phase, throughout which estimates of the fading coefficients are obtained at the legitimate users. In fact, by injecting carefully designed signals during this phase, a man-in-the-middle (MiM) attack could manipulate and control part of the reconciled bits and thus render SKG vulnerable to brute force attacks. Alternatively, a denial of service attack can be mounted by a reactive jammer. In this paper, we investigate the impact of injection and jamming attacks during the advantage distillation in a multiple-input-multiple-output (MIMO) system. First, we show that a MiM attack can be mounted as long as the attacker has one extra antenna with respect to the legitimate users, and we propose a pilot randomization scheme that allows the legitimate users to successfully reduce the injection attack to a less harmful jamming attack. Secondly, by taking a game-theoretic approach we evaluate the optimal strategies available to the legitimate users in the presence of reactive jammers.


Multicenter Diagnostic Accuracy Evaluation of the Luminex Aries Real-Time PCR Assay for Group B Streptococcus Detection in Lim Broth-Enriched Samples.
The vertical transmission of group B Streptococcus (GBS) strains causing neonatal sepsis is one of the leading reasons for neonatal mortality worldwide. The gold standard for GBS detection is enriched culture with or without the aid of chromogenic agars. Given the high risk for morbidity and mortality in this population, high assay sensitivity is required to prevent the personal and economic costs of GBS disease. Nucleic acid amplification tests (NAATs) allow for objective determination of GBS colonization with a sensitivity and a specificity higher than those of traditional culture methods. In this study, we determined the analytical and clinical performance of the Aries GBS assay compared to those of the enrichment culture method, biochemical identification, and the NAATs used at the study sites. Remnant Lim broth samples were used to perform the Aries assay and reference testing. Upon first testing using enriched culture as the reference standard, the Aries GBS assay identified GBS with a 96.1% sensitivity (95% confidence interval [CI], 91.2 to 98.7%) and a 91.4% specificity (95% CI, 88.8 to 93.6%). The test performed with 100% positive agreement (95% CI, 83.2 to 100%) compared to the results of the BD Max GBS assay and 98.0% positive agreement (95% CI, 89.2 to 99.9%) compared to the results of the Cepheid Xpert GBS LB test. Repeatability and reproducibility were maintained in intra- and interlaboratory testing, regardless of the instrument, module, or user who performed the test. The Aries GBS assay can be set up in less than 5 min and produces results in 2 h. The easy setup, with minimal hands-on time, and high assay sensitivity and specificity make this a useful testing option for GBS screening in prepartum women.


Asthma and allergies in Jamaican children aged 2-17 years: a cross-sectional prevalence survey.
To determine the prevalence and severity of asthma and allergies as well as risk factors for asthma among Jamaican children aged 2-17 years. A cross-sectional, community-based prevalence survey using the International Study of Asthma and Allergies in Childhood questionnaire. The authors selected a representative sample of 2017 children using stratified, multistage cluster sampling design using enumeration districts as primary sampling units. Jamaica, a Caribbean island with a total population of approximately 2.6 million, geographically divided into 14 parishes. Children aged 2-17 years, who were resident in private households. Institutionalised children such as those in boarding schools and hospitals were excluded from the survey. The prevalence and severity of asthma and allergy symptoms, doctor-diagnosed asthma and risk factors for asthma. Almost a fifth (19.6%) of Jamaican children aged 2-17 years had current wheeze, while 16.7% had self-reported doctor-diagnosed asthma. Both were more common among males than among females. The prevalence of rhinitis, hay fever and eczema among children was 24.5%, 25% and 17.3%, respectively. Current wheeze was more common among children with rhinitis in the last 12 months (44.3% vs 12.6%, p<0.001), hay fever (36.8% vs 13.8%, p<0.001) and eczema (34.1% vs 16.4%, p<0.001). Independent risk factors for current wheeze (ORs, 95% CI) were chest infections in the first year of life 4.83 (3.00 to 7.77), parental asthma 4.19 (2.8 to 6.08), rhinitis in the last 12 months 6.92 (5.16 to 9.29), hay fever 4.82 (3.62 to 6.41), moulds in the home 2.25 (1.16 to 4.45), cat in the home 2.44 (1.66 to 3.58) and dog in the home 1.81 (1.18 to 2.78). The prevalence of asthma and allergies in Jamaican children is high. Significant risk factors for asthma include chest infections in the first year of life, a history of asthma in the family, allergies, moulds and pets in the home.


[Morphological procedure for rectal cancer].
The morphological study of surgical specimens in rectal cancer involves assessment of the quality of mesorectumectomy, examination of serial sections of a tumor growth area, and study of the proximal, distal, and circulatory ends of resection as a criterion for the quality and efficacy of surgery. The circulatory end of resection is regarded as positive when it has tumor cells inside or within 1 mm of it and the performed surgery is unradical. The data obtained with the use of this technology make it possible to most fully estimate the site and extent of a tumor process, to identify a number of important prognostic factors, and to assess the quality of a performed surgical intervention and preoperative diagnosis. The procedure is adapted to the standard technological equipment of morbid anatomy units.


A rice mutant displaying a heterochronically elongated internode carries a 100 kb deletion.
We have isolated a recessive rice mutant, designated as indeterminate growth (ing), which displays creeping and apparent heterochronic phenotypes in the vegetative period with lanky and winding culms. Rough mapping and subsequent molecular characterization revealed that the ing mutant carries a large deletion, which corresponds to a 103 kb region in the Nipponbare genome, containing nine annotated genes on chromosome 3. Of these annotated genes, the SLR1 gene encoding a DELLA protein is the only one that is well characterized in its function, and its null mutation, which is caused by a single base deletion in the middle of the intronless SLR1 gene, confers a slender phenotype that bears close resemblance to the ing mutant phenotype. The primary cause of the ing mutant phenotype is the deletion of the SLR1 gene, and the ing mutant appears to be the first characterized mutant having the entire SLR1 sequence deleted. Our results also suggest that the deleted region of 103 kb does not contain an indispensable gene, whose dysfunction must result in a lethal phenotype.


Efficient reversible phase mask for TiO2 submicron gratings directly printed on cylindrical surfaces.
In this article we present a radial phase mask specially designed and manufactured for direct micro-structuration under UV photolithography of a cylindrical surface covered by a photoresist TiO2 film. The period of the phase mask is sub-micron (between 480 nm and 720 nm) and allows direct printing on several types of cylindrical components. With this dedicated reversible phase mask we have demonstrated the feasibility of a TiO2 grating with a period of 960 nm, printed on a SiO2 cylinder or inside a SiO2 tube of 8 mm diameter.


Planning for the closure of uncontrolled landfills in Turkey to reduce environmental impacts.
Landfilling is the most preferred solid waste disposal method in Turkey owing to both economic and technical reasons. However, beside the sanitary landfills there are also hundreds of uncontrolled waste sites located throughout Turkey, which are often left either abandoned or burning. Because there is a lack of legislative guidelines governing the closure and rehabilitation of these dumpsites, the municipalities that are responsible for waste management do not initiate the proactive strategies required for the closure of these sites. In this study, a method based on a multi-criteria analysis is conducted for different dumpsites in Turkey to evaluate the level of negative impacts on the environment. This method is based on the use of environmental indices for a quantitative assessment of the landfills, such as environmental interaction between the source and the receptors, environmental values of the receptors, and operational conditions. It was possible to assess the robustness of the proposed methodology since the pre- and post-groundwater quality monitoring data was available from the study sites that were closed and rehabilitated in 2014. The results of this study show that the method based on a multi-criteria analysis is an effective tool while in the preliminary planning stages of closure and rehabilitation activities of uncontrolled waste landfills.


Mechanism of the cardioprotective effects of docetaxel pre-administration against adriamycin-induced cardiotoxicity.
We revealed that pre-treatment with docetaxel (DOC) 12 h before adriamycin (ADR) administration significantly reduced ADR-induced toxic death compared with the simultaneous dosing schedule that was commonly used in previous studies. We considered that pre-treatment with DOC relieves ADR-induced cardiotoxicity. In this study, we investigated the influence of DOC on the pharmacokinetics and pharmacodynamics of ADR in order to clarify the mechanism by which DOC pre-treatment relieves ADR-induced cardiotoxicity. When ADR and/or DOC was intravenously administered, the DOC pre-treatment (DOC-ADR) group showed significantly less toxic death than the ADR-alone group. We examined hepatopathy, nephropathy, leukopenia, and cardiotoxicity, all of which can cause toxic death. Of these toxicities, ADR-induced cardiotoxicity was significantly relieved in the DOC-ADR group. To elucidate the mechanism by which DOC pre-treatment relieved ADR-induced cardiotoxicity, lipid peroxidation as a proxy for the free radical level and the pharmacokinetics of ADR were measured. There was no difference in the pharmacokinetics of ADR between the ADR and DOC-ADR groups. On the other hand, the DOC-ADR group showed significantly inhibited lipid peroxidation in the heart compared with the ADR group. It was considered that DOC pre-administration inhibited ADR-induced free radicals and decreased cardiotoxicity.


Glucose: a vital toxin and potential utility of melatonin in protecting against the diabetic state.
The molecular mechanisms including elevated oxidative and nitrosative reactants, activation of pro-inflammatory transcription factors and subsequent inflammation appear as a unified pathway leading to metabolic deterioration resulting from hyperglycemia, dyslipidemia, and insulin resistance. Consistent evidence reveals that chronically-elevated blood glucose initiates a harmful series of processes in which toxic reactive species play crucial roles. As a consequence, the resulting nitro-oxidative stress harms virtually all biomolecules including lipids, proteins and DNA leading to severely compromised metabolic activity. Melatonin is a multifunctional indoleamine which counteracts several pathophysiologic steps and displays significant beneficial effects against hyperglycemia-induced cellular toxicity. Melatonin has the capability of scavenging both oxygen and nitrogen-based reactants and blocking transcriptional factors which induce pro-inflammatory cytokines. These functions contribute to melatonin's antioxidative, anti-inflammatory and possibly epigenetic regulatory properties. Additionally, melatonin restores adipocyte glucose transporter-4 loss and eases the effects of insulin resistance associated with the type 2 diabetic state and may also assist in the regulation of body weight in these patients. Current knowledge suggests the clinical use of this non-toxic indoleamine in conjunction with other treatments for inhibition of the negative consequences of hyperglycemia for reducing insulin resistance and for regulating the diabetic state.


Respiratory Pattern and Tidal Volumes Differ for Pressure Support and Volume-assured Pressure Support in Amyotrophic Lateral Sclerosis.
Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease resulting in respiratory failure and death. Use of noninvasive ventilation (NIV) improves survival. However, use of volume-assured pressure support (VAPS) has not been extensively studied in ALS. To explore the clinical usefulness of a detailed evaluation of device-recorded NIV data in the management of chronic respiratory failure in ALS, and to determine whether there are differences in efficacy between patients using VAPS or PS. We performed a retrospective chart review of 271 patients with ALS using either PS or VAPS, along with an evaluation of device-recorded data to explore differences in attainment of goal tidal volumes (Vt) and ratio of respiratory rate to tidal volume (f/Vt), in addition to triggering and cycling ability. Two hundred and fifteen patients were using PS, while 56 were using VAPS. There were no significant differences in demographic data, symptoms, pulmonary function, or patient compliance. Compared with VAPS, achieved Vt was significantly lower for PS while f/Vt was significantly higher. Percent spontaneous triggering was relatively preserved in both cohorts, whereas percent spontaneous cycling was considerably decreased in both. Furthermore, there was no association found between spontaneous triggering or cycling, and pulmonary function, indicating the presence of low spontaneous breath cycling or triggering ability is difficult to predict. Examination of device data for exhaled tidal volumes and f/Vt may be of use in evaluating efficacy of NIV in ALS. VAPS provides more reliable goal Vt than does PS, and is associated with decreased f/Vt. Spontaneous cycling is decreased in ALS despite preservation of triggering ability. Although a set backup rate may address decreased triggering, perhaps more importantly, setting a sufficient fixed inspiratory time would address the issue of decreased cycling.


YouTube Videos as a Source of Information About Clinical Trials: Observational Study.
Clinical trials are essential to the advancement of cancer treatment but fewer than 5% of adult cancer patients enroll in a trial. A commonly cited barrier to participation is the lack of understanding about clinical trials. Since the internet is a popular source of health-related information and YouTube is the second most visited website in the world, we examined the content of the top 115 YouTube videos about clinical trials to evaluate clinical trial information available through this medium. YouTube videos posted prior to March 2017 were searched using selected keywords. A snowballing technique was used to identify videos wherein sequential screening of the autofill search results for each set of keywords was conducted. Video characteristics (eg, number of views and video length) were recorded. The content was broadly grouped as related to purpose, phases, design, safety and ethics, and participant considerations. Stepwise multivariable logistic regression analysis was conducted to assess associations between video type (cancer vs noncancer) and video characteristics and content. In total, 115 videos were reviewed. Of these, 46/115 (40.0%) were cancer clinical trials videos and 69/115 (60.0%) were noncancer/general clinical trial videos. Most videos were created by health care organizations/cancer centers (34/115, 29.6%), were oriented toward patients (67/115, 58.3%) and the general public (68/115, 59.1%), and were informational (79/115, 68.7%); altruism was a common theme (31/115, 27.0%). Compared with noncancer videos, cancer clinical trials videos more frequently used an affective communication style and mentioned the benefits of participation. Cancer clinical trial videos were also much more likely to raise the issue of costs associated with participation (odds ratio [OR] 5.93, 95% CI 1.15-29.46) and advise patients to communicate with their physician about cancer clinical trials (OR 4.94, 95% CI 1.39-17.56). Collectively, YouTube clinical trial videos provided information on many aspects of trials; however, individual videos tended to focus on selected topics with varying levels of detail. Cancer clinical trial videos were more emotional in style and positive in tone and provided information on the important topics of cost and communication. Patients are encouraged to verify and supplement YouTube video information in consultations with their health care professionals to obtain a full and accurate picture of cancer clinical trials to make an adequately informed decision about participation.


The neuropeptidergic connectome of C. elegans.
Efforts are ongoing to map synaptic wiring diagrams, or connectomes, to understand the neural basis of brain function. However, chemical synapses represent only one type of functionally important neuronal connection; in particular, extrasynaptic, "wireless" signaling by neuropeptides is widespread and plays essential roles in all nervous systems. By integrating single-cell anatomical and gene-expression datasets with biochemical analysis of receptor-ligand interactions, we have generated a draft connectome of neuropeptide signaling in the C. elegans nervous system. This network is characterized by high connection density, extended signaling cascades, autocrine foci, and a decentralized topology, with a large, highly interconnected core containing three constituent communities sharing similar patterns of input connectivity. Intriguingly, several key network hubs are little-studied neurons that appear specialized for peptidergic neuromodulation. We anticipate that the C. elegans neuropeptidergic connectome will serve as a prototype to understand how networks of neuromodulatory signaling are organized.


Multidetector CT urography in urogenital tuberculosis: use of reformatted images for the assessment of the radiological findings. A pictorial essay.
Urogenital tuberculosis (UGTB) is the most common form of extrapulmonary TB and is responsible for a destructive inflammation of the renal parenchyma and urinary tract often leading to the loss of kidney function. For these reasons, the early diagnosis of this disease, once considered disappeared in developed countries, is very important to establish a prompt and efficient treatment. However, the subtle and non-specific symptoms, often represented by recurrent and persistent lower urinary tract symptoms, can confound and delay the diagnosis. Therefore, an adequate and comprehensive imaging study is necessary in patients with persistent urinary tract infections not responding to the antibiotics and can suggest the hypothesis although bacteriological and/or histologic analysis is required for a definitive diagnosis. In the past years, intravenous urography (IVU) has allowed a comprehensive study of the urinary excretory tract, promoting the knowledge of the radiological findings of this disease. Nowadays, computed tomography urography (CTU), with the implementation of multidetector (MD) technology, has replaced IVU in all its indications; the MDCTU improves the assessment of renal and urinary tract lesions using reformatted images [such as multiplanar reconstruction (MPR) and maximum intensity projection (MIP)]. Therefore, our paper aims to provide a guide for radiologist for searching the classic signs of UGTB on MDCTU, encouraging the use of the MPR and MIP reformatted images.


Corncob bedding alters the effects of estrogens on aggressive behavior and reduces estrogen receptor-α expression in the brain.
There is growing appreciation that estrogen signaling pathways can be modulated by naturally occurring environmental compounds such as phytoestrogens and the more recently discovered xenoestrogens. Many researchers studying the effects of estrogens on brain function or behavior in animal models choose to use phytoestrogen-free food for this reason. Corncob bedding is commonly used in animal facilities across the United States and has been shown to inhibit estrogen-dependent reproductive behavior in rats. The mechanism for this effect was unclear, because the components of corncob bedding mediating this effect did not bind estrogen receptors. Here, we show in the California mouse (Peromyscus californicus) that estrogens decrease aggression when cardboard-based bedding is used but that this effect is absent when corncob bedding is used. California mice housed on corncob bedding also had fewer estrogen receptor-α-positive cells in the bed nucleus of the stria terminalis and ventromedial hypothalamus compared with mice housed on cardboard-based bedding. In addition, corncob bedding suppressed the expression of phosphorylated ERK in these brain regions as well as in the medial amygdala and medial preoptic area. Previous reports of the effects of corncob bedding on reproductive behavior are not widely appreciated. Our observations on the effects of corncob bedding on behavior and brain function should draw attention to the importance that cage bedding can exert on neuroendocrine research.


[Patient-reported SEFAS: Questionnaire good evaluation method in foot and ankle disorders].
There is need for structured evaluation of disability before and after surgery. The patients' subjective aspects of their symptoms should be one part of this evaluation, preferably captured by patient-reported outcome measures (PROMs). There are several PROMs, either generic or region-specific questionnaires, but no » gold standard « for foot or ankle evaluation. We translated the Self-reported Foot and Ankle Score (SEFAS) and evaluated the psychometric properties of the score in terms of reliability, validity and responsiveness in patients with a variety of foot and ankle disorders. In this report we recommend a validation process for PROMs and report that SEFAS shows good results when doing this. As SEFAS is a PROM, the instrument seems suitable for use in national registers.


Neutral genetic markers and conservation genetics: simulated germplasm collections.
This study examines the use of neutral genetic markers to guide sampling from a large germplasm collection with the objective of establishing from it a smaller, but genetically representative sample. We simulated evolutionary change and germplasm sampling in a subdivided population of a diploid hermaphrodite annual plant to create an initially large collection. Several strategies of sampling from this collection were then compared. Our results show that a strategy based on information obtained from marker genes led to retention of the maximum number of neutral and nonneutral alleles in the smaller sample. This occurred when demes were composed of self-fertilizing individuals or when no migration occurred among demes, but not when demes of an outcrossing population were connected by high levels of migration.


Pituicytoma with gelsolin amyloid deposition.
Pituicytoma is a rare low-grade (WHO grade I) sellar region glioma. Among sellar tumors, pituitary adenomas, mainly prolactinomas, may show amyloid deposits. Gelsolin is a ubiquitous calcium-dependent protein that regulates actin filament dynamics. Two known gene point mutations result in gelsolin amyloid deposition, a characteristic feature of a rare type of familial amyloid polyneuropathy (FAP), the Finnish-type FAP, or hereditary gelsolin amyloidosis (HGA). HGA is an autosomal-dominant systemic amyloidosis, characterized by slowly progressive neurological deterioration with corneal lattice dystrophy, cranial neuropathy, and cutis laxa. A unique case of pituicytoma with marked gelsolin amyloid deposition in a 67-year-old Chinese woman is described. MRI revealed a 2.6-cm well-circumscribed, uniformly contrast-enhancing solid sellar mass with suprasellar extension. Histologically, the lesion was characterized by solid sheets and fascicles of spindle cells with slightly fibrillary cytoplasm and oval nuclei with pinpoint nucleoli. Surrounding brain parenchyma showed marked reactive piloid gliosis. Remarkably, conspicuous amyloid deposits were identified as pink homogeneous spherules on light microscopy that showed apple-green birefringence on Congo red with polarization. Mass spectrometric-based proteomic analysis identified the amyloid as gelsolin type. Immunohistochemically, diffuse reactivity to S100 protein and TTF1, focal reactivity for GFAP, and no reactivity to EMA, synaptophysin, and chromogranin were observed. HGA-related mutations were not identified in the tumor. No recurrence was noted 14 months after surgery. To the knowledge of the authors, amyloid deposition in pituicytoma or tumor-associated gelsolin amyloidosis has not been previously described. This novel finding expands the spectrum of sellar tumors that may be associated with amyloid deposition.


Arenavirus chemotherapy--retrospect and prospect.
Two groups of compounds, identifiable by structural similarity, have been found to interfere with the in vitro replication of arenaviruses. All 4 members of the benzimidazole group contain dipolar fused benzene and 5-membered nitrogen-containing rings and share potential chelating ability through the different bidentate structures formed with their side-chains. The biological activity of one of these compounds, metisazone, has been shown to depend on the presence of divalent metals of the first transition series, Cu(++) being the most effective. Furthermore, whereas metisazone inactivates cell-free virus, two other members of the group, HBB and 1,2-bis(5-methoxy-1H-benzimidazol-2-yl)-1,2-ethanediol, act intracellularly. The site of action of the fourth member, SKF 30097, is not known. Using murine lymphocytic choriomeningitis infections as an in vivo model, the bisbenzimidazole derivative has been found to increase life-span without interfering with virus replication. Medication with SKF 30097 or metisazone and copper (2(+)) sulfate did not significantly or reproducibly change the expected day of death of the animals. The amantadine compounds of the second group have unusual symmetric structures with a 10-carbon cage. The parent compound acts intracellularly, while the site of action of an octachloro derivative is not known. Medication with the parent compound, but not the derivative, shortened the interval between LCM infection and death of the mouse. Tissue culture and animal screening of the many available derivatives in these two groups may uncover compounds more efficacious than those already examined.


The filamentous phage pIV multimer visualized by scanning transmission electron microscopy.
A family of homomultimeric outer-membrane proteins termed secretins mediates the secretion of large macromolecules such as enzymes and filamentous bacteriophages across bacterial outer membranes to the extracellular milieu. The secretin encoded by filamentous phage f1 was purified. Mass determination of individual molecules by scanning transmission electron microscopy revealed two forms, a unit multimer composed of about 14 subunits and a multimer dimer. The secretin is roughly cylindrical and has an internal diameter of about 80 angstroms, which is large enough to accommodate filamentous phage (diameter of 65 angstroms).


Chronic tendinopathy tissue pathology, pain mechanisms, and etiology with a special focus on inflammation.
Continuing progress in research in molecular biology and biomechanics has provided considerable new information and has given rise to new hypotheses in chronic tendinopathy. Overloading is still, however, crucial in the development of tendinopathy. Most of the histologic findings in tendinopathy represent chronic degeneration, regeneration, and microtears of the tendinous tissue. The prevailing opinion is that no histological evidence of acute inflammation has been documented, but in newer studies using immunohistochemistry and flow cytometry inflammatory cells have been detected. The existing data indicate that the initiators of the tendinopathic pathway include many proinflammatory agents (e.g. cytokines, prostaglandins, different growth factors, and neuropetides). Because of the complex interaction between the classic proinflammatory agents and the neuropeptides, it seems impossible and somewhat irrelevant to distinguish sharply between chemical and neurogenic inflammation. Furthermore, glucocorticoids are, at the moment, the most effective treatment in tendinopathy with regard to reduction of pain, tendon thickness, and neovascularization. This review indicates - despite a great deal of uncertainty regarding the concepts - that an inflammatory process may be related not only to the development of tendinopathy but also chronic tendinopathy. More attention should be directed towards the "tendinitis myth" in the future.


Comparison of 2f1-f2 DPOAE and 2f2-f1 DPOAE fine structure in young and middle-aged adults.
The 2f2-f1 DPOAE is not as popular as the 2f1-f2 DPOAE in the clinical realm as it is not as robust. However, it does have an advantage of being a predominantly reflection emission. The reflection component has been found to be sensitive to cochlear damage. Our objective was to compare the two types of DPOAE to track subtle changes due to aging. We used the most suitable stimulus parameters to record the fine structures of 2f2-f1 DPOAE and 2f1-f2 DPOAE for comparison in two groups of individuals. Young adults and middle-aged adults with normal hearing sensitivity participated in the experiment. Both ears of all participants were tested. Although reductions were noted in the both types of DPOAE in the middle-aged participants compared with the young adults, the decrease in amplitude of the 2f2-f1 DPOAE was found to be statistically significant. This corresponded with statistically significant reductions in the reflection component of the 2f1-f2 DPOAE. Reductions in the 2f2-f1 DPOAE were found with both, high-level and low-level primaries. These results highlight the advantages of analysing fine structure data of the 2f2-f1 DPOAE to track subtle cochlear changes in response to aging.


The effect of nimodipine on cerebral oxygenation in patients with poor-grade subarachnoid hemorrhage.
Nimodipine has been shown to improve neurological outcome after subarachnoid hemorrhage (SAH); the mechanism of this improvement, however, is uncertain. In addition, adverse systemic effects such as hypotension have been described. The authors investigated the effect of nimodipine on brain tissue PO2. Patients in whom Hunt and Hess Grade IV or V SAH had occurred who underwent aneurysm occlusion and had stable blood pressure were prospectively evaluated using continuous brain tissue PO2 monitoring. Nimodipine (60 mg) was delivered through a nasogastric or Dobhoff tube every 4 hours. Data were obtained from 11 patients and measurements of brain tissue PO2, intracranial pressure (ICP), mean arterial blood pressure (MABP), and cerebral perfusion pressure (CPP) were recorded every 15 minutes. Nimodipine resulted in a significant reduction in brain tissue PO2 in seven (64%) of 11 patients. The baseline PO2 before nimodipine administration was 38.4+/-10.9 mm Hg. The baseline MABP and CPP were 90+/-20 and 84+/-19 mm Hg, respectively. The greatest reduction in brain tissue PO2 occurred 15 minutes after administration, when the mean pressure was 26.9+/-7.7 mm Hg (p < 0.05). The PO2 remained suppressed at 30 minutes (27.5+/-7.7 mm Hg [p < 0.05]) and at 60 minutes (29.7+/-11.1 mm Hg [p < 0.05]) after nimodipine administration but returned to baseline levels 2 hours later. In the seven patients in whom brain tissue PO2 decreased, other physiological variables such as arterial saturation, end-tidal CO2, heart rate, MABP, ICP, and CPP did not demonstrate any association with the nimodipine-induced reduction in PO2. In four patients PO2 remained stable and none of these patients had a significant increase in brain tissue PO2. Although nimodipine use is associated with improved outcome following SAH, in some patients it can temporarily reduce brain tissue PO2.


[Encopresis in children, the view of child psychiatry].
The article aims to provide a state of knowledge in the literature on encopresis in the child psychiatric population. The general definition of the symptom and its analysis are presented according to different approaches. Then, the clinic of encopresis is described according to its specificities. The main associated disorders and psychiatric/psychosocial risk factors are discussed in detail. Regarding patient care, the multidisciplinary approach, including the complementarity with the paediatrician, is essential in a number of cases. Finally, family approach and the impact of trauma would be interesting research perspectives.


Gamma-aminobutyric acid (GABA)-mediated bone formation and its implications for anti-osteoporosis strategies: Exploring the relation between GABA and GABA receptors.
Osteoporosis is a significant global health concern, linked to reduced bone density and an increased fracture risk, with effective treatments still lacking. This study explored the potential of gamma-aminobutyric acid (GABA) and its receptors as a novel approach to promote osteogenesis and address osteoporosis. GABA concentrations up to 10 mM were well-tolerated by MC3T3-E1 preosteoblast, stimulating osteoblast differentiation and mineralization in a concentration- and time-dependent manner. In vivo experiments with zebrafish larvae demonstrated the ability of GABA to improve vertebral formation and enhanced bone density, indicating the potential therapeutic value for osteoporosis. Notably, GABA countered the adverse effects of prednisolone on vertebral formation, bone density, and osteogenic gene expression in zebrafish larvae, suggesting a promising therapeutic solution to counteract corticosteroid-induced osteoporosis. Moreover, our study highlighted the involvement of GABA receptors in mediating the observed osteogenic effects. By using GABAA, GABAB, and GABAC receptor antagonists, we demonstrated that blocking these receptors attenuated GABA-induced osteoblast differentiation and vertebral formation in both MC3T3-E1 cells and zebrafish larvae, underscoring the importance of GABA receptor interactions in promoting bone formation. In conclusion, these findings underscore the osteogenic potential of GABA and its ability to mitigate the detrimental effects of corticosteroids on bone health. Targeting GABA and its receptors could be a promising strategy for the development of novel therapeutic interventions to address osteoporosis. However, further investigations are warranted to fully elucidate the underlying molecular mechanism of GABA and its clinical applications in treating osteoporosis.


Does the fly matter? the CRACKPOT study in evidence based trout fishing. The Collaborative Randomised and Controlled Kennet Piscatorial Options Trail (CRACKPOT) Investigators.
To investigate the importance of the type of dry fly (artificial floating fly) in catching trout (brown and rainbow) in an English chalkstream. River Kennet, Berkshire. Five anglers on five separate occasions spent five hours using a randomly allocated fly from a sample of five types. Five anglers of considerable but varying experience, determination, and opinion. Number, weight, and species of trout caught. One fly (Black Gnat) performed significantly worse than the others. The fly most successful in catching brown trout was the Cinnamon Sedge. The possible prolongation of doctors' leisure time consequent on the use of unproductive trout flies has resource implications for the NHS. Urgent funding of a definitive, large multiriver trial is needed.


Gene Regulatory Enhancers with Evolutionarily Conserved Activity Are More Pleiotropic than Those with Species-Specific Activity.
Studies of regulatory activity and gene expression have revealed an intriguing dichotomy: There is substantial turnover in the regulatory activity of orthologous sequences between species; however, the expression level of orthologous genes is largely conserved. Understanding how distal regulatory elements, for example, enhancers, evolve and function is critical, as alterations in gene expression levels can drive the development of both complex disease and functional divergence between species. In this study, we investigated determinants of the conservation of regulatory enhancer activity for orthologous sequences across mammalian evolution. Using liver enhancers identified from genome-wide histone modification profiles in ten diverse mammalian species, we compared orthologous sequences that exhibited regulatory activity in all species (conserved-activity enhancers) to shared sequences active only in a single species (species-specific-activity enhancers). Conserved-activity enhancers have greater regulatory potential than species-specific-activity enhancers, as quantified by both the density and diversity of transcription factor binding motifs. Consistent with their greater regulatory potential, conserved-activity enhancers have greater regulatory activity in humans than species-specific-activity enhancers: They are active across more cellular contexts, and they regulate more genes than species-specific-activity enhancers. Furthermore, the genes regulated by conserved-activity enhancers are expressed in more tissues and are less tolerant of loss-of-function mutations than those targeted by species-specific-activity enhancers. These consistent results across various stages of gene regulation demonstrate that conserved-activity enhancers are more pleiotropic than their species-specific-activity counterparts. This suggests that pleiotropy is associated with the conservation of regulatory across mammalian evolution.


Accuracy of computed tomography detection of superior canal dehiscence.
High-resolution temporal bone computed tomography (CT) may erroneously demonstrate a superior semicircular canal dehiscence (SSCD) where none exists and inaccurately display the size of a dehiscence. CT is an integral component of the diagnosis of SSCD. The prevalence of dehiscence as measured on computed tomographic scan is approximately eightfold higher than that on histologic studies, suggesting that CT may have a relatively low specificity for identifying canal dehiscence. This, in turn, can lead to an inappropriate diagnosis and treatment plan. We quantified the accuracy of CT in identifying a dehiscence of the superior semicircular canal in a cadaver model using microCT as a gold standard. The superior canals of 11 cadaver heads were blue lined. Twelve of the 22 ears were further drilled to create fenestrations of varying sizes. Heads were imaged using medical CT, followed by microCT scans of the temporal bones at 18-µm resolution. Diagnosis of dehiscence and measurements of dehiscence size were performed on clinical CT and compared with that of microCT. Clinical CT identified 7 of 8 intact canals as dehiscent and tended to overestimate the size of smaller fenestrations, particularly those surrounded by thin bone. These findings confirm that medical CT cannot be used as the exclusive gold standard for SSCD and that, particularly for small dehiscences on CT, clinical symptoms must be clearly indicative of a dehiscence before surgical treatment is undertaken. Preoperative counseling for small dehiscences may need to include the possibility that no dehiscence may be found despite radiologic evidence for it.


Development of a high slip-resistant footwear outsole using a hybrid rubber surface pattern.
The present study examined whether a new footwear outsole with tread blocks and a hybrid rubber surface pattern, composed of rough and smooth surfaces, could increase slip resistance and reduce the risk of fall while walking on a wet floor surface. A drag test was performed to measure static and dynamic coefficient of friction (SCOF and DCOF, respectively) values for the footwear with the hybrid rubber surface pattern outsole and two types of commercially available boots that are conventionally used in food factories and restaurant kitchens with respect to a stainless steel floor covered with glycerol solution. Gait trials were conducted with 14 participants who wore the footwear on the wet stainless steel floor. The drag test results indicated that the hybrid rubber surface pattern sole exhibited higher SCOF (≥0.44) and DCOF (≥0.39) values than the soles of the comparative footwear (p<0.001). Because of such high SCOF and DCOF values, the slip frequency (p<0.01), slip distance (p<0.001), and slip velocity (p<0.001) for the footwear with the hybrid rubber surface pattern outsole were significantly lower than those for the comparative footwear, which resulted in no falls during trials.


Chemical composition of barley and co-products from barley, corn, and wheat produced in South-East Asia or Australia.
A study was conducted to determine the chemical composition of barley and co-products from barley, corn, and wheat produced in South-East Asia or Australia, and to test the hypothesis that production area or production methods can impact the chemical composition of wheat co-products. Samples included seven barley grains, two malt barley rootlets, one corn gluten feed, one corn gluten meal, one corn bran, eight wheat brans, one wheat mill mix, and four wheat pollards. All samples were analyzed for dry matter, gross energy, nitrogen, amino acids (AA), acid hydrolyzed ether extract (AEE), ash, minerals, starch, and insoluble and soluble dietary fiber. Malt barley rootlets and wheat co-products were also analyzed for sugars. Chemical composition of barley, malt barley rootlets, and corn co-products were in general similar across countries. Wheat pollard had greater (p<0.05) concentrations of tryptophan, magnesium, and potassium compared with wheat bran, whereas wheat bran had greater (p<0.05) concentration of copper than wheat pollard. There were no differences in chemical composition between wheat bran produced in Australia and wheat bran produced in Thailand. Intact barley contains more starch, but fewer AA, than grain co-products. There were only few differences in the composition of wheat bran and wheat pollard, indicating that the two ingredients are similar, but with different names. However, corn gluten meal contains more protein and less fiber than corn bran.


Early indication of emergence from vegetative state derived from assessments with the SMART--a preliminary report.
An explanatory analysis of data from serial assessments of 30 patients with a diagnosis of vegetative state (persistent vegetative state) was carried out. The data were gathered using the Sensory Modality Assessment and Rehabilitation Technique (SMART) and the Western Neuro Sensory Stimulation Profile (WNSSP) on the same day in the week post-admission and, thereafter, at 2 monthly intervals. Seven patients emerged from vegetative state during the study, a further six emerged later (by time of the analysis) and the rest remained in vegetative state. Recovery scores were calculated for each measure by subtracting the total score at any one assessment from the total score for the subsequent assessment; the largest recovery scores, shown by each patient, were noted. It was found that those who emerged later could be differentiated mathematically from those who did not emerge, using largest recovery score data from the SMART. This research supports previous


Screening for iron overload in the Turkish population.
Hereditary hemochromatosis (HH), the most common autosomal recessive disease in the white population, is characterized by excessive gastrointestinal absorption of iron and loading of parenchymal organs. HFE mutations of C282Y and H63D are largely responsible for HH in populations of Celtic ancestry. Although many screening studies related to HH have been done in Northern Europe, the USA and Australia, as yet, no such study has been published on Turkey. In this study we aimed to screen the Turkish population for iron overload. Random samples were obtained from 4,633 healthy adults (3,827 male, 806 female, mean age +/- SD 35 +/- 8 years, range 14-76) for the measurement of transferrin saturation (TS). Measurements were repeated after an overnight fast in the subjects whose initial TS was > or =50%. Serum ferritin levels and C282Y and H63D gene mutations were studied in cases when fasting TS was > or =50%. In cases where the serum ferritin level was >200 ng/ml with or without HFE mutations, liver biopsy was performed for histological evaluation and determination of iron content. In 158 subjects, TS was > or =50% in the non-fasting state. A second determination of TS after an overnight fast was performed in 135 subjects. In 26 subjects, the TS was > or =50% in the fasting state. HFE mutation and serum ferritin levels were measured in these 26 subjects. Eleven subject (10 male, 1 female) were heterozygote and 1 male subject was homozygote in reference to H63D. C282Y mutation was not found. Four of these 26 subjects (all males, aged 23, 24, 40, 49) had increased serum ferritin levels and liver biopsy was performed. In 1 male (aged 49) who was heterozygote for H63D genotype with a serum ferritin level of 645 ng/ml, iron overload in liver tissue was shown by histology as well as atomic absorption spectrophotometry. The prevalence of hemochromatosis in the Turkish population is much lower in comparison to populations of Celtic ancestry and C282Y mutation is non-existent.


Chronic Ly49H Receptor Engagement in vivo Decreases NK Cell Response to Stimulation Through ITAM-Dependent and Independent Pathways Both in vitro and in vivo.
Natural killer (NK) cells play an important role in the innate immune response. The summation of activation and inhibitory signals delivered through cell surface membrane receptors determines NK cell function. However, the continuous engagement of an activating receptor on NK cells appears to render the cells hyporesponsive to stimulation through other unrelated activating receptors. The mechanism by which this takes place remains unclear. Herein we demonstrate that continuous in vivo engagement of the Ly49H receptor with its ligand, m157, results in Ly49H+ NK cells that are hyporesponsive to further stimulation by other ITAM-dependent and independent receptors, while Ly49H- NK cells remain unaffected. The hyporesponsiveness of the NK cell correlates with the degree of Ly49H receptor downmodulation on its cell surface. We observe defects in calcium flux in the hyporesponsive NK cells following stimulation through the NK1.1 receptor. In addition, we observe differences in signaling molecules that play a role in calcium flux, including spleen tyrosine kinase (Syk) at baseline and phosphorylated phospholipase C gamma 2 (p-PLCγ2) at both baseline and following stimulation through NK1.1. We also demonstrate that various ITAM associated activation receptors, including Ly49H, remain associated with their respective adaptor molecules. With regard to in vivo NK cell function, we did not find differences in the formation of metastatic lung lesions following IV injection of B16 melanoma cells. However, we did observe defects in rejection of missing-self targets in vivo. The data suggest that continuous engagement of the Ly49H activating receptor on NK cells results in hyporesponsiveness of the NK cells to all of the ITAM-dependent and independent receptors we analyzed due to altered signaling pathways downstream of the receptor and adaptor molecule.


Protein phosphatase 1 and phosphatase 1 nuclear targeting subunit-dependent regulation of DNA-dependent protein kinase and non-homologous end joining.
DNA-dependent protein kinase catalytic subunit (DNA-PKcs) plays a key role in mediating non-homologous end joining (NHEJ), a major repair pathway for DNA double-strand breaks (DSBs). The activation, function and dynamics of DNA-PKcs is regulated largely by its reversible phosphorylation at numerous residues, many of which are targeted by DNA-PKcs itself. Interestingly, these DNA-PKcs phosphorylation sites function in a distinct, and sometimes opposing manner, suggesting that they are differentially regulated via complex actions of both kinases and phosphatases. In this study we identified several phosphatase subunits as potential DSB-associated proteins. In particular, protein phosphatase 1 (PP1) is recruited to a DSB-mimicking substrate in Xenopus egg extracts and sites of laser microirradiation in human cells. Depletion of PP1 impairs NHEJ in both Xenopus egg extracts and human cells. PP1 binds multiple motifs of DNA-PKcs, regulates DNA-PKcs phosphorylation, and is required for DNA-PKcs activation after DNA damage. Interestingly, phosphatase 1 nuclear targeting subunit (PNUTS), an inhibitory regulator of PP1, is also recruited to DNA damage sites to promote NHEJ. PNUTS associates with the DNA-PK complex and is required for DNA-PKcs phosphorylation at Ser-2056 and Thr-2609. Thus, PNUTS and PP1 together fine-tune the dynamic phosphorylation of DNA-PKcs after DNA damage to mediate NHEJ.


Maximum growth rate of Mycobacterium avium in continuous culture or chronically infected BALB/c mice.
Mycobacterium avium is a human pathogen which may cause either chronic or disseminated disease and the organism exhibits a slow rate of growth. This study provides information on the growth rate of the organism in chronically infected mice and its maximal growth rate in vitro. M. avium was grown in continuous culture, limited for nitrogen with 0.5 mM ammonium chloride and dilution rates that ranged from 0.054 to 0.153 h-1. The steady-state concentration of ammonia nitrogen and M. avium cells for each dilution rate were determined. The bacterial saturation constant for growth-limiting ammonia was 0.29 mM (4 micrograms nitrogen/ml) and, from this, the maximal growth rate for M. avium was estimated to be 0.206 h-1 or a doubling time of 3.4 h. BALB/c mice were infected intravenously with 3 x 10(6) colony-forming units and a chronic infection resulted, typical of virulent M. avium strains. During a period of 3 months, the number of mycobacteria remained constant in the lungs, but increased 30-fold and 8,900-fold, respectively, in the spleen and mesenteric lymph nodes. The latter increase appeared to be due to proliferation in situ. The generation time of M. avium in the mesenteric lymph nodes was estimated to be 7 days.


Family-mediated exercise intervention (FAME): evaluation of a novel form of exercise delivery after stroke.
Additional exercise therapy has been shown to have a positive impact on function after acute stroke and research is now focusing on methods to increase the amount of therapy that is delivered. This randomized controlled trial examined the impact of additional family-mediated exercise (FAME) therapy on outcome after acute stroke. Forty participants with acute stroke were randomly assigned to either a control group who received routine therapy with no formal input from their family members or a FAME group, who received routine therapy and additional lower limb FAME therapy for 8 weeks. The primary outcome measure used was the lower limb section of the Fugl-Meyer Assessment modified by Lindmark. Other measures of impairment, activity, and participation were completed at baseline, postintervention, and at a 3-month follow-up. Statistically significant differences in favor of the FAME group were noted on all measures of impairment and activity postintervention (P<0.05). These improvements persisted at the 3-month follow-up but only walking was statistically significant (P<0.05). Participants in the FAME group were also significantly more integrated into their community at follow-up (P<0.05). Family members in the FAME group reported a significant decrease in their levels of caregiver strain at the follow-up when compared with those in the control group (P<0.01). This evidence-based FAME intervention can serve to optimize patient recovery and family involvement after acute stroke at the same time as being mindful of available resources.


Plants with stacked genetically modified events: to assess or not to assess?
The principles for the safety assessment of genetically modified (GM) organisms (GMOs) are harmonised worldwide to a large extent. There are, however, still differences between the European GMO regulations and the GMO regulations as they have been formulated in other parts of the world. One of these differences relates to the so-called 'stacked GM events', that is, GMOs, plants so far, where new traits are combined by conventional crossing of different GM plants. This paper advocates rethinking the current food/feed safety assessment of stacked GM events in Europe based on an analysis of different aspects that currently form the rationale for the safety assessment of stacked GM events.


Longitudinal survey of rotavirus infection in calves.
A longitudinal survey of rotavirus infection in heifer calves was carried out on a closed Friesian dairy herd over two successive calving seasons. Rotavirus was detected by electron microscopy in the faeces of 45 of 57 (79 per cent) calves examined. On average the virus was first detected at 6.1 days of age. Clinically the disease associated with rotavirus infection was of mild to moderate severity. Only one infected calf required intravenous fluid therapy. Diarrhoea or excretion of abnormal faeces was associated with rotavirus infection in 58 per cent of infected calves, while in the remaining 42 per cent infection was subclinical. The cycle of rotavirus infection was broken by thorough cleansing and disinfection of the calf house.


Toxicity of a quartz with occluded surfaces in a 90-day intratracheal instillation study in rats.
This 90-day study was aimed at characterizing the differences in biological activity between a crystalline ground reference quartz (DQ12) and a quartz with occluded surfaces (quartz isolate) obtained from a clay deposit formed 110 to 112 million years ago. In different test groups, rats were dosed with the same total mass and quartz level by intratracheal instillation, with a total high dose of 15.2 mg/kg (body weight, bw) or approximately 4.7 mg/rat of each quartz species in a saline suspension. The reference quartz was mixed with titanium dioxide to achieve a positive control mixture, which contained the same quartz content as in the quartz isolate. At 3 days post dosing, both quartz groups showed a significant inflammatory response based on total and differential cell counts from bronchoalveolar lavageate (BAL) analysis. At 28 and 90 days, the quartz isolate values were no longer statistically different from vehicle control group values; however, the positive control group values were approximately 12 and 65 times greater than those of the control group, respectively. After 28 days, histopathological evaluation showed moderate effects in the quartz isolate group compared to the saline control animals. These effects did not progress in severity at 90 days. In contrast, the positive control group exhibited more severe effects than the quartz isolate group and these effects showed a progression to a persistent and self-perpetuating inflammatory state. The toxicological properties of quartz particles can vary significantly dependent on their surface characteristics. Toxicity can range from a high-dose-induced, modest, transient inflammation from quartz with occluded surfaces, to a severe and persistent inflammatory state caused by ground quartz with fractured surfaces.


Mortality and healthcare resource utilisation after cardiac arrest in the United States - A 10-year nationwide analysis prior to the COVID-19 pandemic.
Understanding the public health burden of cardiac arrest (CA) is important to inform healthcare policies, particularly during healthcare crises such as the COVID-19 pandemic. This study aimed to analyse outcomes of in-hospital mortality and healthcare resource utilisation in adult patients with CA in the United States over the last decade prior to the COVID-19 pandemic. The United States (US) National Inpatient Sample was utilised to identify hospitalised adult patients with CA between 2010 and 2019. Logistic and Poisson regression models were used to analyse outcomes by adjusting for 47 confounders. 248,754 adult patients with CA (without "Do Not Resuscitate"-orders) were included in this study, out of which 57.5% were male. In-hospital mortality was high with 51.2% but improved significantly from 58.3% in 2010 to 46.4% in 2019 (P < 0.001). Particularly, elderly patients, non-white patients and patients requiring complex therapy had a higher mortality rate. Although the average hospital LOS decreased by 11%, hospital expenses have increased by 13% between 2010 and 2019 (each P < 0.001), presumably due to more frequent use of mechanical circulatory support (MCS, e.g. ECMO from 2.6% to 8.7% or Impella® micro-axial flow pump from 1.8% to 14.2%). Strong disparities existed among patient age groups and ethnicities across the US. Of note, the number of young adults with CA and opioid-induced CA has almost doubled within the study period. Over the last ten years prior to the COVID-19 pandemic, CA-related survival has incrementally improved with shorter hospitalisations and increased medical expenses, while strong disparities existed among different age groups and ethnicities. National standards for CA surveillance should be considered to identify trends and differences in CA treatment to allow for standardised medical care.


[Perspective modeling of coronary bypass surgery].
Mammary coronary bypass surgeries were performed in canine experiments. Myocardial perfusion was done via a shunt passing within the mammary artery and inserted into the distal portion of a coronary artery through a section, avoiding the application of extracorporeal circulation and myocardial ischemia. The method creates stenoses in any area of a vessel unit. A relationship was examined between coronary blood flow, left ventricular and aortic pressures by using a mathematical model that covers the effects of such parameters as resistance of great vessels, their capacity, minor vascular resistance, blood flow arrest and extravascular compression pressures on coronary blood flow.


The protease allergen Pen c 13 induces allergic airway inflammation and changes in epithelial barrier integrity and function in a murine model.
Fungal allergens are associated with the development of asthma, and some have been characterized as proteases. Here, we established an animal model of allergic airway inflammation in response to continuous exposure to proteolytically active Pen c 13, a major allergen secreted by Penicillium citrinum. In functional analyses, Pen c 13 exposure led to increased airway hyperresponsiveness, significant inflammatory cell infiltration, mucus overproduction, and collagen deposition in the lung, dramatically elevated serum levels of total IgE and Pen c 13-specific IgE and IgG1, and increased production of the Th2 cytokines IL-4, IL-5, and IL-13 by splenocytes stimulated in vitro with Pen c 13. To examine the mechanisms involved in the regulation of allergenicity by Pen c 13, we performed two-dimensional fluorescence difference gel electrophoresis analysis combined with nano-LC-MS/MS, followed by bioinformatics analysis to identify potential targets that associated with allergic inflammation, which suggested that galectin-3 and laminin might be involved in novel pathogenic mechanisms. Finally, we focused on junctional proteins between cells, because, in addition to opening of the epithelial barrier by environmental proteases possibly being the initial step in the development of asthma, these proteins are also associated with actin rearrangement. Taken together, our findings indicate that Pen c 13 exposure causes junctional structure alterations and actin cytoskeletal rearrangements, resulting in increased permeability and airway structural changes. These effects probably change the lung microenvironment and foster the development of allergic sensitization.


Molecular maps of neural activity and quiescence.
The rapid accumulation of inducible transcription factors (ITFs), such as c-Fos and Zif268, in activated neurons combined with histological methods that offer detection at the cellular level are key features that have led to their wide use in visualizing activated neurons. There are two major drawbacks of ITFs that limit their use in the CNS--cell-type expression specificity and stimulus-transcription coupling uncertainty. Recent technical advances in the field of molecular activity mapping now permit dual-labeling approaches that help resolve some of these ambiguities and identify neurons that are activated by different sensory stimuli. Furthermore, the recent identification of the robl/LC7-like gene, which shows immediate-early repression after stimulation, may have utility in functional mapping where it can be used to delineate quiescent neurons and serve as a complement to molecular activity markers.


Treatment of sialocele: an experimental study in dogs.
A patient had a delayed complication of parotid trauma, namely a sialocele. He was successfully treated by repeated needle aspiration of the fluid. An experiment using 30 dogs was then done. On each dog, one parotid gland was used as a control, the other parotid was treated by one of three methods that the author felt would be most satisfactory. Needle aspiration was found to be the simplest and the most effective manner of treatment, because the proximal duct quickly becomes obstructed with the cessation of salivary flow, disappearance of the sialocele, and later parotid atrophy. One patient and 30 dogs are surely not conclusive proof of what would be proper treatment, but the author hopes that this paper will stimulate otolaryngologists to try this method if confronted with a similar problem.


Applying machine learning to facilitate autism diagnostics: pitfalls and promises.
Machine learning has immense potential to enhance diagnostic and intervention research in the behavioral sciences, and may be especially useful in investigations involving the highly prevalent and heterogeneous syndrome of autism spectrum disorder. However, use of machine learning in the absence of clinical domain expertise can be tenuous and lead to misinformed conclusions. To illustrate this concern, the current paper critically evaluates and attempts to reproduce results from two studies (Wall et al. in Transl Psychiatry 2(4):e100, 2012a; PloS One 7(8), 2012b) that claim to drastically reduce time to diagnose autism using machine learning. Our failure to generate comparable findings to those reported by Wall and colleagues using larger and more balanced data underscores several conceptual and methodological problems associated with these studies. We conclude with proposed best-practices when using machine learning in autism research, and highlight some especially promising areas for collaborative work at the intersection of computational and behavioral science.


Linking global drivers of agricultural trade to on-the-ground impacts on biodiversity.
Consumption of globally traded agricultural commodities like soy and palm oil is one of the primary causes of deforestation and biodiversity loss in some of the world's most species-rich ecosystems. However, the complexity of global supply chains has confounded efforts to reduce impacts. Companies and governments with sustainability commitments struggle to understand their own sourcing patterns, while the activities of more unscrupulous actors are conveniently masked by the opacity of global trade. We combine state-of-the-art material flow, economic trade, and biodiversity impact models to produce an innovative approach for understanding the impacts of trade on biodiversity loss and the roles of remote markets and actors. We do this for the production of soy in the Brazilian Cerrado, home to more than 5% of the world´s species. Distinct sourcing patterns of consumer countries and trading companies result in substantially different impacts on endemic species. Connections between individual buyers and specific hot spots explain the disproportionate impacts of some actors on endemic species and individual threatened species, such as the particular impact of European Union consumers on the recent habitat losses for the iconic giant anteater (Myrmecophaga tridactyla). In making these linkages explicit, our approach enables commodity buyers and investors to target their efforts much more closely to improve the sustainability of their supply chains in their sourcing regions while also transforming our ability to monitor the impact of such commitments over time.


Unravelling the story of protein misfolding in diabetes mellitus.
Both environmental and genetic factors contribute to the development of diabetes mellitus and although monogenic disorders are rare, they offer unique insights into the fundamental biology underlying the disease. Mutations of the insulin gene or genes involved in the response to protein misfolding cause early onset diabetes. These have revealed an important role for endoplasmic reticulum stress in β-cell survival. This form of cellular stress occurs when secretory proteins fail to fold efficiently. Of all the professional secretory cells we possess, β-cells are the most sensitive to endoplasmic reticulum stress because of the large fluctuations in protein synthesis they face daily. Studies of endoplasmic reticulum stress signaling therefore offer the potential to identify new drug targets to treat diabetes.


Comparison of the Flotac-400 dual technique and the formalin-ether concentration technique for diagnosis of human intestinal protozoon infection.
There is a need for accurate diagnosis of intestinal parasite infections in humans, but currently available copromicroscopic techniques have shortcomings, such as low sensitivity. We compared the diagnostic accuracy of a further modified version of the recently developed Flotac technique with that of the widely used formalin-ether concentration technique (FECT) for the detection of intestinal protozoa in human stool samples. Formaldehyde-preserved stool samples from 108 individuals in Côte d'Ivoire were subjected to the Flotac-400 dual technique, using two different flotation solutions (FS), and to the FECT. Stool samples were examined according to computer-generated random lists by an experienced laboratory technician blinded for the results of each method. Both methods detected the same eight intestinal protozoon species. While the Flotac-400 dual technique (results from both FS combined) found higher prevalences of Entamoeba coli (77.8% versus 71.3%, P < 0.001), Blastocystis hominis (20.4% versus 13.0%, P = 0.458), and Giardia intestinalis (8.3% versus 6.5%, P < 0.001), the FECT detected higher prevalences of Entamoeba histolytica/Entamoeba dispar (27.8% versus 20.4%, P = 0.019) and four species of nonpathogenic intestinal protozoa. The diagnostic agreement between the two methods differed considerably depending on the intestinal protozoon investigated (Cohen's kappa measures; range, 0.01 to 0.46). Our study confirmed that the Flotac-400 dual technique can be utilized for the diagnosis of intestinal protozoon infections in humans. Since Flotac is a sensitive technique for the detection of soil-transmitted helminths and Schistosoma mansoni, it might become a viable copromicroscopic technique for the concurrent diagnosis of helminths and intestinal protozoon infections.


Do cMOAT (MRP2), other MRP homologues, and LRP play a role in MDR?
The discovery of the Multidrug Resistance-associated Protein (MRP or MRP1) as a GS-X pump able to transport both anionic drug conjugates and unmodified anti-cancer drugs out of the cell, has raised the question whether other members of the MRP family might contribute to drug resistance of human tumours. The most extensively studied member of this family is cMOAT, the canalicular Multispecific Organic Anion Transporter. The substrate specificity of this pump was originally defined by an inborn error in rats, lacking this protein. These rats are mildly hyperbilirubinemic, because of their inability to secrete bilirubin glucuronides into their bile. In addition, they have diminished capacity to secrete a variety of other organic anions. Absence of cMOAT in humans results in an analogous inborn error of metabolism, the Dubin-Johnson syndrome. Attempts to determine the effect of cMOAT on the sensitivity of cells to anti-cancer drugs have run into technical problems. Most cells transfected with a cMOAT cDNA construct and overproducing cMOAT seem unable to transport the protein to the cell surface and are not MDR. However, in polarized kidney cell monolayers cMOAT is correctly routed to the apical cell surface and able to transport vinblastine. Hence, overexpression of cMOAT in cancer cells could potentially lead to drug resistance. In studies of cells selected for drug resistance no correlation was found thus far between cMOAT overexpression and MDR, but there was a positive association with cisplatin resistance, raising the possibility that cMOAT might contribute to cisplatin resistance by mediating excretion of cisplatin-glutathione complexes. This remains to be verified by more direct experiments and clinical studies, however. Database searches have yielded four additional MRP family members, MRP3-6. The physiological functions of these putative transporters are not yet known and whether they can contribute to drug resistance needs to be determined. Another putative transporter found in many MDR cells not overproducing P-glycoprotein is the Lung Resistance Protein (LRP), which is the major vault protein. Scheper et al have detected LRP in many MDR cell lines and they have shown that elevated LRP values are a strong and independent predictor of unfavourable outcome for several types of drug-treated human tumours. LRP is a cytoplasmic protein and attempts to demonstrate its involvement in drug transport have failed thus far. The possibility that this protein is only an indicator of resistance caused by upregulation of other proteins, rather than a drug transporter, remains open.


Experience in the first four years of rapid recovery; is it safe?
The average length of hospital stay after Total Hip Replacement (THR) has been decreasing over time. Recently, many hospitals have commenced rapid recovery programs such as Joint Care. In Joint Care the patients are usually discharged on the fifth post-operative day with relatively fresh surgical wounds. The aim of this study is to evaluate the Joint Care program after THR. Between February 2000 and February 2004, the Joint Care program was used in 611 patients after THR. The average age of the patients was 66.3 yrs (SD 9.3; range 24-86 yrs) and 68% (n= 415) of them were female. All clinical and outpatient charts as well as nursery records were evaluated. The follow up was from 6 months to 4 years (average: 2.5 years). At the planned fifth post-operative day, 92% (n = 562) of patients were discharged from hospital (SD 1.7 days; range 6-25 days). 3.8% (n= 23) of the remaining cases faced wound problems--prolonged wound drainage in 2.3% (n = 14) and potential superficial infection in 1.5% (n = 9) - causing a delay in their discharge. The readmission rate was 6.4% (n = 39) due to hip dislocation (3.4%; n = 21), re-evaluation of wound (1.5%; n= 9), deep infection (1.2%; n = 7)) and cardiac events (0.3%; n = 2). All the infection cases were treated effectively with debridement and antibiotics and no revision for any reason was reported. The Joint Care program seems to be effective after THR. Post-operative hip dislocation was the main reason for post-operative readmission. However, no clear signs that the intensive rehabilitation program caused more complications compared to previous regimens were evident. The above results encourage the application of rapid recovery programs in Orthopaedic surgery and joint replacement.


Increased expression of NOS and ET-1 immunoreactivity in human colorectal metastatic liver tumours is associated with selective depression of constitutive NOS immunoreactivity in vessel endothelium.
The absence of perivascular nerves in tumour vessels suggests that endothelium derived vasoactive substances [nitric oxide (NO) and endothelin-1 (ET-1)] may be key factors in controlling tumour blood flow during tumour growth and metastasis. We have studied the ultrastructural distribution and immunoreactivity of different NO synthase (NOS) isoforms and ET-1 in human colorectal metastatic liver tumour tissues using pre-embedding peroxidase-anti-peroxidase and post-embedding immunoelectron microscopic triple gold labelling techniques. Dramatically lower NOS 1 immunoreactivity was observed in tumour vascular endothelium (1-3% and 15-20% in tumour and normal groups, respectively). As compared to control groups there were significantly less NOS3 immunopositive EC in metastatic tumour vessels (45-50% and 1-3% in normal and tumour groups, respectively). A striking rise in NOS2 was observed in tumour vessel endothelium (< 1% in normal and 65-70% in tumour vessel endothelium). ET-1 immunoreactivity levels were also significantly higher in tumour vessel endothelium (85-90% in tumour, 15-20% in normal group). This increased expression of NOS2 and ET-1 immunoreactivity was accompanied by the increased expression of three NOS isoforms and ET-1 immunoreactivity in liver parenchymal cells. These data suggest that metastatic tumour vessel endothelium is characterized by increased expression of NOS2 and ET-1 and by decreases in NOS1 and NOS3. These characteristics are associated with the overexpression of all three NOS isoforms and ET-1 immunoreactivity in non-vascular cells.


OFraMP: a fragment-based tool to facilitate the parametrization of large molecules.
An Online tool for Fragment-based Molecule Parametrization (OFraMP) is described. OFraMP is a web application for assigning atomic interaction parameters to large molecules by matching sub-fragments within the target molecule to equivalent sub-fragments within the Automated Topology Builder (ATB, atb.uq.edu.au) database. OFraMP identifies and compares alternative molecular fragments from the ATB database, which contains over 890,000 pre-parameterized molecules, using a novel hierarchical matching procedure. Atoms are considered within the context of an extended local environment (buffer region) with the degree of similarity between an atom in the target molecule and that in the proposed match controlled by varying the size of the buffer region. Adjacent matching atoms are combined into progressively larger matched sub-structures. The user then selects the most appropriate match. OFraMP also allows users to manually alter interaction parameters and automates the submission of missing substructures to the ATB in order to generate parameters for atoms in environments not represented in the existing database. The utility of OFraMP is illustrated using the anti-cancer agent paclitaxel and a dendrimer used in organic semiconductor devices. OFraMP applied to paclitaxel (ATB ID 35922).


CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to granulocyte-macrophage colony-stimulating factor plus tumor necrosis factor alpha: II. Functional analysis.
In response to granulocyte-macrophage colony-stimulating factor plus tumor necrosis factor alpha, cord blood CD34+ hematopoietic progenitor cells differentiate along two unrelated dendritic cell (DC) pathways: (1) the Langerhans cells (LCs), which are characterized by the expression of CD1a, Birbeck granules, the Lag antigen, and E cadherin; and (2) CD14+ cell-derived DCs, characterized by the expression of CD1a, CD9, CD68, CD2, and factor XIIIa (Caux et al, J Exp Med 184:695, 1996). The present study investigates the functions of each population. Although the two populations are equally potent in stimulating naive CD45RA cord blood T cells through apparently identical mechanisms, each also displays specific activities. In particular CD14-derived DCs show a potent and long-lasting (from day 8 to day 13) antigen uptake activity (fluorescein isothiocyanate dextran or peroxidase) that is about 10-fold higher than that of CD1a+ cells, which is restricted to the immature stage (day 6). The antigen capture is exclusively mediated by receptors for mannose polymers. The high efficiency of antigen capture of CD14-derived cells is coregulated with the expression of nonspecific esterase activity, a tracer of lysosomial compartment. In contrast, the CD1a+ population never expresses nonspecific esterase activity. The most striking difference is the unique capacity of CD14-derived DCs to induce naive B cells to differentiate into IgM-secreting cells, in response to CD40 triggering and interleukin-2. Thus, although the two populations can allow T-cell priming, initiation of humoral responses might be preferentially regulated by the CD14-derived DCs. Altogether, those results show that different pathways of DC development might exist in vivo: (1) the LC type, which might be mainly involved in cellular immune responses, and (2) the CD14-derived DC related to dermal DCs or circulating blood DCs, which could be involved in humoral immune responses.


Conjugated linoleic acids suppress inflammatory response and ICAM-1 expression through inhibition of NF-κB and MAPK signaling in human bronchial epithelial cells.
Conjugated linoleic acids (CLAs) comprise a group of natural unsaturated fatty acids. CLA was reported to have anti-asthma, anti-adiposity, and anti-tumor effects. The present study aimed to evaluate the suppressive effects of cis-9, trans-11-CLA (c9,t11-CLA) on the expression of proinflammatory cytokines and intercellular adhesion molecule 1 (ICAM-1) in TNF-α-stimulated human bronchial epithelial (BEAS-2B) cells. After treating with various doses of c9,t11-CLA (12.5-100 μg ml(-1)), BEAS-2B cells were induced into an inflamed state by adding TNF-α or TNF-α/IL-4. The presence of c9,t11-CLA significantly suppressed the secretion of cytokines IL-6, IL-8, CCL5, and MCP-1. We also found that c9,t11-CLA inhibited ICAM-1 expression, and decreased monocyte adhesion to inflamed bronchial epithelial cells. Interestingly, c9,t11-CLA attenuated the phosphorylation of mitogen-activated protein kinase (MAPK) and down-regulated the activation of nuclear factor-κB (NF-κB). These results suggested that the anti-inflammatory effects of c9,t11-CLA were mediated by inhibiting proinflammatory cytokines, chemokines, and ICAM-1 expression by blocking NF-κB transcription regulation and by attenuating MAPK signaling pathways.


[Not Available].
B. Landi Gastrointestinal stromal tumors (GISTs) are the most frequent intramural mesenchymal tumors of the GI tract, mainly developed in the stomach (65% of cases). Endoscopy is the main diagnostic tool for tumors of moderate diameter (<5cm). Endoscopic ultrasonography (EUS) is the best procedure to differenciate GISTs from other submucosal tumors. Fine-needle aspiration biopsies (FNABs) allow to obtain an histological diagnosis if necessary. Surgery remain the gold standard of treatment for localized GISTs, whereas endoscopic resection is not recommended for these tumors.


Hereditary gynaecological malignancies: advances in screening and treatment.
In the last two decades there have been significant advances in our understanding of female genital tract tumours. The discovery of BRCA1 and BRCA2 genes in ovarian cancer and the mismatch repair genes in endometrial carcinoma has revolutionized our approach to the diagnosis and screening of women for ovarian and uterine cancers. This review discusses the pathogenesis of these two hereditary syndromes in depth and explains how the molecular genetics is tailoring the manner in which these diseases are diagnosed and potentially treated. Other, less common hereditary conditions associated with gynaecological tract manifestations, such as Cowden syndrome, Peutz-Jeghers syndrome, Gorlin syndrome and hereditary leiomyomatosis and renal cell carcinoma, are also summarized briefly.