Use of antihistamines after serious allergic reaction to methimazole in pediatric Graves' disease.
Antithyroid drugs are usually considered first-line therapy for management of pediatric Graves' disease because they avoid permanent hypothyroidism, provide a chance for remission, and are less invasive than the alternatives of thyroidectomy or radioactive iodine. Methimazole (MMI) is the only antithyroid drug recommended in pediatrics due to the risk of propylthiouracil-induced liver toxicity. Allergic reactions with MMI occur in up to 10% of patients and, when mild, can be managed with concurrent antihistamine therapy. Guidelines recommend discontinuation of MMI with serious allergic reactions. We present the case of an adolescent girl with Graves' disease and a serious allergic reaction after starting MMI whose family refused radioactive iodine and was reluctant to proceed to surgery. Antihistamine therapy was successfully used to allow continued treatment with MMI. This case demonstrates extension of management guidelines for minor cutaneous allergic reactions to MMI, through the use of antihistamines for a serious allergic reaction, allowing us to continue MMI and provide treatment consistent with the family's preferences and values.


Pricing distortions in Medicare's physician fee schedule and patient satisfaction with care quality and access.
Medicare adjusts its payments to physicians for geographic differences in the cost of operating a medical practice, but the method it uses is imprecise. We measure the inaccuracy in its geographic adjustment factors and categorize beneficiaries by whether they live where Medicare's formula is favorable or unfavorable to physicians. Then, using the 2001-2003 Medicare Current Beneficiary Survey, we examine whether differences in physician payment generosity, that is, whether favorable or unfavorable, influence the satisfaction ratings Medicare seniors assign to their quality of care and access to services. We find strong evidence that they do. Many beneficiaries live in payment-unfavorable areas and receive a less satisfying quality of care and less satisfying access to services than beneficiaries who live where payments are favorable to physicians.


Faster forgetting contributes to impaired spatial memory in the PDAPP mouse: deficit in memory retrieval associated with increased sensitivity to interference?
Two experiments were conducted to investigate the possibility of faster forgetting by PDAPP mice (a well-established model of Alzheimer's disease as reported by Games and colleagues in an earlier paper). Experiment 1, using mice aged 13-16 mo, confirmed the presence of a deficit in a spatial reference memory task in the water maze by hemizygous PDAPP mice relative to littermate controls. However, after overtraining to a criterion of equivalent navigational performance, a series of memory retention tests revealed faster forgetting in the PDAPP group. Very limited retraining was sufficient to reinstate good memory in both groups, indicating that their faster forgetting may be due to retrieval failure rather than trace decay. In Experiment 2, 6-mo-old PDAPP and controls were required to learn each of a series of spatial locations to criterion with their memory assessed 10 min after learning each location. No memory deficit was apparent in the PDAPP mice initially, but a deficit built up through the series of locations suggestive of increased sensitivity to interference. Faster forgetting and increased interference may each reflect a difficulty in accessing memory traces. This interpretation of one aspect of the cognitive deficit in human mutant APP mice has parallels to deficits observed in patients with Alzheimer's disease, further supporting the validity of transgenic models of the disease.


Cryo-EM structure of the CFA/I pilus rod.
Enterotoxigenic Escherichia coli (ETEC) are common agents of diarrhea for travelers and a major cause of mortality in children in developing countries. To attach to intestinal cells ETEC express colonization factors, among them CFA/I, which are the most prevalent factors and are the archetypical representative of class 5 pili. The helical quaternary structure of CFA/I can be unwound under tensile force and it has been shown that this mechanical property helps bacteria to withstand shear forces from fluid motion. We report in this work the CFA/I pilus structure at 4.3 Å resolution from electron cryomicroscopy (cryo-EM) data, and report details of the donor strand complementation. The CfaB pilins modeled into the cryo-EM map allow us to identify the buried surface area between subunits, and these regions are correlated to quaternary structural stability in class 5 and chaperone-usher pili. In addition, from the model built using the EM structure we also predicted that residue 13 (proline) of the N-terminal β-strand could have a major impact on the filament's structural stability. Therefore, we used optical tweezers to measure and compare the stability of the quaternary structure of wild type CFA/I and a point-mutated CFA/I with a propensity for unwinding. We found that pili with this mutated CFA/I require a lower force to unwind, supporting our hypothesis that Pro13 is important for structural stability. The high-resolution CFA/I pilus structure presented in this work and the analysis of structural stability will be useful for the development of novel antimicrobial drugs that target adhesion pili needed for initial attachment and sustained adhesion of ETEC.


[Psychoemotional strain on pilots prior to ejection and its role in adequate performance].
It was demonstrated that with respect to the psychoemotional state real and simulated catapulting events were similar. The time-course variations in the latent period of the motor reaction were obtained. The time interval between the command "Go" and the catapulting event was found to increase significantly in relation to the latent period. This was correlated with the level of psychoemotional strain.


Overexpression of LncRNA PVT1 Predicts Advanced Clinicopathological Features and Serves as an Unfavorable Risk Factor for Survival of Patients with Gastrointestinal Cancers.
Many studies have reported that PVT1 played important roles in diverse cancer types. But the systematic analysis of PVT1 in gastrointestinal cancers has not been inspected. Thus, we aimed to investigate clinical value of the long noncoding RNA PVT1 (lncRNA) expression in digestive system cancers. Eligible studies were collected from a number of databases (PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure and Wanfang database). Pooled hazard ratio (HR) or odds ratio (OR) with 95 % confidence interval (95 % Cl) were applied to assess the clinical significance of PVT1. Data from 15 articles were included with a total of 2585 patients. Elevated PVT1 expression were significantly related to poor overall survival (OS) [HR = 1.86, 95% CI (1.44, 2.28); p<0. 0001] in digestive system cancers. The same association was also observed between PVT1 expression with outcomes, including disease free survival (DFS), disease specific survival (DSS) and relapse free survival (RFS). The lncRNA PVT1 could also be predicative for some clinicopathological features. This meta-analysis revealed that PVT1 may serve as a prognostic predictor and pathological biomarker in digestive system cancers.


Seroprevalence of foot-and-mouth disease virus in cattle herds raised in Maasai Mara ecosystem in Kenya.
A cross-sectional study was carried out to determine foot-and-mouth disease (FMD) seroprevalence and identify risk factors of exposure among cattle herds raised in three zones with different types of land use and progressively distant from the Maasai Mara National Reserve (MMNR) boundary. We selected five villages purposively; two in zone 1 (area < 20 km from the MMNR), another two in zone 2 (area between 20-40 km away from the MMNR) and one in zone 3 (area >40 km away from the MMNR). A total of 1170 cattle sera were collected from 390 herds in all the zones and tested for antibodies against the non-structural proteins (NSPs) of FMD virus (FMDV) using two 3ABC-based Enzyme-Linked Immunosorbent Assay ELISA kits. All sera samples were also screened for serotype-specific antibodies using Solid Phase Competitive ELISA (SPCE) kits (IZSLER, Italy). We targeted FMDV serotypes A, O, South African Territory [SAT] 1 and SAT 2, known to be endemic in East Africa including Kenya. Data on putative risk factors for FMD seropositivity in cattle were collected using a questionnaire. The overall apparent animal-level FMD seroprevalence based on the parallel comparison of the two anti-NSPs ELISA kits was 83.8 % (95 % CI; 81.8-85.9), and differed significantly across zones. Zone 1 had a higher seroprevalence than zones 2 and 3 (χ2 = 116.1, df = 2, p < 0.001). In decreasing order, the overall seroprevalences of FMDV serotypes A, SAT 2, O and SAT 1 were 26.3 % (95 % CI; 23.5-29.2), 21.4 % (95 % CI; 18.8-24.0), 21.2 % (95 % CI; 18.7-23.9) and 13.1 % (95 % CI; 11.1-15.3), respectively. The distribution of these serotypes differed significantly between zones (p < 0.05) except for SAT 2 serotype (χ2 = 0.90, df = 2, p = 0.639). Both serotypes A and O were more prevalent in zones 1 and 2 than zone 3 while serotype SAT 1, was higher in zone 3 compared to other zones. The results of multivariable analyses identified animal sex (i.e., female), raising of cattle in zones 1 and 2 (areas < 40 km away from the MMNR); mixing of cattle from multiple herds at watering points, and pastoral husbandry practices, as significant predictors of animal-level FMD seropositivity. This study established that FMD seroprevalence declined with distance from the MMNR.


What are the important components of the clinical assessment of hand problems in older adults in primary care? Results of a Delphi study.
To identify clinical questions and assessments regarded by health care practitioners as important when assessing undifferentiated hand pain or problems in adults aged 50 years and over presenting to primary care. A purposively selected panel of 26 UK-based Health Care Practitioners comprising occupational therapists, physiotherapists, rheumatologists and general practitioners, were invited to take part in a consensus study involving three postal rounds of a Delphi questionnaire with accompanying case scenarios. Participants were asked to generate questions and assessments (round 1), rate their importance (round 2), and vote on which items were most important (round 3). Sixteen Health Care Practitioners agreed to participate with 11 completing all three rounds. The first round of the Delphi study generated 156 questions and 143 assessments. After three rounds agreement was reached on the importance of 25 questions and 19 assessments. Questions were weighted towards current symptoms, but also included the history of previous hand problems, self-reported hand function, co-morbidity and general health. Observation and palpation of features predominated in the choice of assessment, but specific tests, grip strength, evaluation of sensation and hand function were also included. A pool of clinical questions and assessments were generated by Health Care Practitioners, and those considered most important for assessing older adults presenting with undifferentiated hand pain and hand problems in primary care were identified. Further evaluation is required to establish the reliability and feasibility of using these questions and assessments in primary care. In particular, the relative contribution of these questions and assessments in evaluating the nature and severity of hand problems, assisting diagnosis, indicating appropriate management, and predicting future course requires further investigation.


[Lateralization of saccadic latency during monocular presentation of stimuli to a leading and non-leading eye].
Saccadic latencies were studied in ten healthy subjects. Peripheral targets were presented monocularly to a leading and nonleading eyes in the right and left hemifields. SS (single step) and OVERLAP (200 ms) schemes of visual stimulation were used. Under OVERLAP conditions, the saccadic latency was longer by 30-39 ms and the number of long-latency saccades was higher than under SS conditions, especially in subjects with mixed asymmetry profiles. In the majority of subjects with right asymmetry profile, the latencies of saccades during stimulation of the leading eye were by 12 ms shorter than during stimulation of the nonleading eye, and the latencies of right saccades were by 24 ms shorter than that of the left saccades independently of the stimulated eye. The obtained results explain some characteristic features of hemyspheric asymmetry in organization of saccadic movements.


Speech and language therapy interventions for children with cleft palate: a systematic review.
Objective : (1) To examine the evidence for the effectiveness of differences in timing and type of speech and language therapy for children with cleft palate with or without a cleft lip and (2) to identify types of interventions assessed. Design : Nine databases, including MEDLINE and EMBASE, were searched between inception and March 2011 to identify published articles relating to speech and language therapy for children with cleft palate with or without cleft lip. Studies that included at least 10 participants and reported outcome measures for speech and/or language measures were included. Studies where the experimental group had less than 90% of children with cleft palate with or without cleft lip were excluded. Two reviewers independently completed inclusion assessment, data extraction, and risk of bias assessment for all studies identified. Results : A total of 17 papers were evaluated: six randomized control trials and 11 observational studies. Studies varied widely on risk of bias, intervention used, and outcome measures reported. None of the studies had a low risk of bias. In terms of intervention approaches, seven studies evaluated linguistic approaches and 10 evaluated motor approaches. Outcomes measures did not support either approach over the other, and based on data reported it was difficult to ascertain which approach is more effective for children with cleft palate with or without cleft lip. Conclusions : The review found little evidence to support any specific intervention. Key uncertainties need to be identified and adequately powered, methodologically rigorous studies conducted to provide a secure evidence base for speech-language therapy practice in children with cleft palate with or without cleft lip.


Treatment of Middle Third Humeral Shaft Fractures with Anteromedial Plate Osteosynthesis through an Anterolateral Approach.
Background: Treatment of humeral shaft fractures has been a subject of debate for many decades. Even though a large majority of humeral shaft fractures can be treated by non operative methods, few conditions like open fractures, polytrauma, ipsilateral humeral shaft and forearm fractures require surgical intervention. The goal of treatment of humeral shaft fractures is to establish union with an acceptable humeral alignment and to restore the patient to pre-injury level of function. The objective was to assess the incidence of radial nerve palsy, non-union and mean time required for in anteromedial plate osteosynthesis with anterolateral approach and also to measure the functional outcome of this procedure. Method: A prospective study was conducted in the Department of Orthopaedics, PESIMSR, Kuppam, Andhra Pradesh, from August 2012 to August 2015 with a total of 54 patients who were operated with anteromedial plate osteosynthesis were included in the study. Rodriguez- Merchan criteria was used to grade the functional outcome. Results: Of the 54 patients, 28 (58.85%) were in the age group of 30-40 years. The most common fracture pattern identified was A3 type (48.14%).The mean (± SD) duration of surgery for anteromedial humeral plating was 53 ± 5.00 minutes. The time taken for the fracture to unite was less than 16 weeks in the majority or 50 patients (92.59%). Four (7.40%) patients had delayed union. There was no incidence of iatrogenic radial nerve palsy. Rodriguez - Merchan criteria showed that 37(68.51%) of the patients had good and 12 (22.22%) had excellent functional outcome.


Vasodilatory actions of alpha-human atrial natriuretic peptide and high Ca2+ effects in normal man.
To study vascular actions of synthetic alpha-human atrial natriuretic polypeptide (alpha hANP) in man, forearm blood flow (FBF) was measured by strain-gauge plethysmograph during the continuous infusion of 100 ng/min alpha hANP dissolved in 5% dextrose into the brachial artery in healthy subjects. alpha hANP increased FBF, with the concomitant increase in ipsilateral limb venous plasma concentrations of alpha hANP. Overall, there was a significant linear correlation between the decrements of ipsilateral forearm vascular resistance (FVR) during infusions of alpha hANP and initial FVR levels (r = -0.883, P less than 0.01). Moreover, alpha hANP, at the stepwise increasing doses of 20, 100, and 500 ng/min, increased FBF in a dose-related fashion: alpha hANP elicits a concentration-dependent vasodilation of forearm vascular beds. Concomitantly, infusions of alpha hANP caused a dose-dependent increase in ipsilateral limb venous plasma cyclic guanosine monophosphate (cyclic GMP). Overall, there were direct correlations of FBF either to ipsilateral venous plasma alpha hANP (r = 0.724, P less than 0.01) or to cyclic GMP concentrations (r = 0.637, P less than 0.01). Subsequently, isoosmolar CaCl2 solution was infused into the same brachial artery at a rate of 0.09 meq/min, and then, with a 2.5 +/- 0.2-mg/dl increase in ipsilateral venous serum calcium concentrations the incremental responses of both FBF and plasma cyclic GMP to alpha hANP were severely blunted. There was also a significant positive linear correlation between FBF and venous plasma cyclic GMP during infusions of alpha hANP with the simultaneous administration of CaCl2 (r = 0.807, P less than 0.01). Finally, the addition of CaCl2 infusion did not change the slope of the regression line of the FBF-plasma cyclic GMP relationship during infusions of alpha hANP. Evidence presented suggests that alpha hANP acts directly on the forearm vascular beds in man, eliciting its vascular relaxant effect, possibly by increasing cellular levels of cyclic GMP. Moreover, modest elevations of serum calcium inhibit the alpha hANP-dependent vasodilation, possibly through the suppression of cyclic GMP activation.


Development of a new model system to study microbial colonization on dentures.
Dentures are often colonized with a variety of microorganisms, including Candida albicans, that contribute to denture stomatitis. Several in vitro models have been previously established to study denture-related microbial colonization and evaluate treatment efficacy of denture cleansers; however, those models typically fail to appreciate the complex topology and heterogeneity of denture surfaces and lack effective ways to accurately measure microbial colonization. The purpose of this study was to study microbial colonization with a new model system based on real dentures, to more realistically mimic in vivo conditions. Scanning electron microscopy was used to observe topological structures among surfaces from different parts of the denture. Employing C. albicans as a model microorganism, we established microbial colonization on different denture surfaces. Moreover, we applied a modified MTT (3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) colorimetric assay to quantify C. albicans colonization on dentures without the necessity of biofilm removal and to evaluate treatment efficacy of denture cleansers. There were significant variations in topological structures among surfaces from different parts of the denture, with the unpolished side having the highest amounts of indentations and pores. The distinct denture surfaces support microbial colonization differently, with the unpolished side containing the highest level of microbial colonization and biofilm formation. Furthermore, the modified MTT colorimetric assay proved to be an accurate assay to measure biofilm formation on dentures and evaluate treatment efficacy of denture cleansers. This new denture model system in conjunction with the MTT colorimetric assay is a valuable tool to study denture-related microbiology and treatment approaches.


Allelic variation of the β-, γ- and δ-kafirin genes in diverse Sorghum genotypes.
The β-, γ- and δ-kafirin genes were sequenced from 35 Sorghum genotypes to investigate the allelic diversity of seed storage proteins. A range of grain sorghums, including inbred parents from internationally diverse breeding programs and landraces, and three wild Sorghum relatives were selected to encompass an extensive array of improved and unimproved germplasm in the Eusorghum. A single locus exists for each of the expressed kafirin-encoding genes, unlike the multigenic α-kafirins. Significant diversity was found for each locus, with the cysteine-rich β-kafirin having four alleles, including the first natural null mutant reported for this prolamin subfamily. This allele contains a frame shift insertion at +206 resulting in a premature stop codon. SDS-PAGE revealed that lines with this allele do not produce β-kafirin. An analysis of flour viscosity reveals that these β-kafirin null lines have a difference in grain quality, with significantly lower viscosity observed over the entire Rapid ViscoAnalyser time course. There was less diversity at the protein level within the cysteine-rich γ-kafirin, with only two alleles in the cultivated sorghums. There were only two alleles for the δ-kafirin locus among the S. bicolor germplasm, with one allele encoding ten extra amino acids, of which five were methionine residues, with an additional methionine resulting from a nucleotide substitution. This longer allele encodes a protein with 19.1% methionine. The Asian species, S. propinquum, had distinct alleles for all three kafirin genes. We found no evidence for selection on the three kafirin genes during sorghum domestication even though the δ-kafirin locus displayed comparatively low genetic variation. This study has identified genetic diversity in all single copy seed storage protein genes, including a null mutant for β-kafirin in Sorghum.


[Myocarditis in childhood: results of a decade's research].
The research of the last decade gave new insights in the pathogenesis of viral myocarditis. The virus infection of the myocardium may be controlled by the infiltrating inflammatory cells and heal with more or less scarring. An autoimmune mediated chronic inflammation is observed as well as the persistence of virus genoms, which causes with low replication rate again chronic inflammation. The immunohistochemical characterization of the infiltrating immune cells and the molecular biological proof of virus genoms in endomyocardial specimens allow a sensitive diagnostic of the various forms of myocarditis and should guide therapy. Until now treatment trials did not differentiate between these various forms, had no control groups or very small numbers of patients. Two multicenter treatment trials in Germany referring to immunosuppressive or interferon therapy in children and adults may give--provided a better participation--recommendations for therapy.


Glucagon-like peptide-1-responsive catecholamine neurons in the area postrema link peripheral glucagon-like peptide-1 with central autonomic control sites.
Glucagon-like peptide-1 (GLP-1) released from the gut is an incretin that stimulates insulin secretion. GLP-1 is also a brain neuropeptide that has diverse central actions, including inhibition of food and water intake, gastric emptying, and stimulation of neuroendocrine responses characteristic of visceral illness. Both intravenous and intracerebroventricular administration of GLP-1 receptor (GLP-1R) agonists increase blood pressure and heart rate and induce Fos-like immunoreactivity (Fos-IR) in autonomic regulatory sites in the rat brain. The area postrema (AP) is a circumventricular organ and has been implicated in processing visceral sensory information. GLP-1Rs are densely expressed in the AP, and peripheral GLP-1R agonists induce Fos-IR in AP neurons to a greater degree than intracerebroventricular administration. Because the AP lacks a blood-brain barrier, we hypothesized that the AP is a key site for peripheral GLP-1 to activate central autonomic regulatory sites. In this study, we found that many tyrosine hydroxylase (TH)-containing neurons in the AP expressed GLP-1Rs and Fos-IR after intravenous GLP-1R agonists. Furthermore, intravenous but not intracerebroventricular GLP-1R agonists induced TH transcription in the AP in vivo. In addition, GLP-1R agonists directly activated TH transcription in an in vitro cell system. Finally, we found that GLP-1-responsive TH neurons in the AP innervate autonomic control sites, including the parabrachial nucleus, nucleus of solitary tract, and ventrolateral medulla. These findings suggest that catecholamine neurons in the AP link peripheral GLP-1 and central autonomic control sites that mediate the diverse neuroendocrine and autonomic actions of peripheral GLP-1.


Restricted Sensitivity of FJ-C Staining to Assess Neuronal Degeneration and Death in Preclinical Mouse Studies.
Fluorescein-derived fluorochromes and anionic dyes such as Fluoro-Jade (FJ) stains have been introduced to facilitate recognition of dying neurons in tissue sections. However, the definition of what is really detected by FJ-based stains and its sensitivity in the detection of neuronal cell death is unclear. In our work, we evaluated the outcome of FJ-C staining in mouse brains from 4 different well-characterized models of neurodegeneration. Neuronal degeneration and loss were highlighted with high sensitivity by FJ-C stain in mice with dysfunctional γ-secretase in the glutamatergic neurons and in mice affected by acute cerebral ischemia. Histopathologically, acute eosinophilic necrosis or "red dead" neurons were associated with FJ-C staining in both settings. Conversely, in mice affected by chronic cerebral microinfarcts due to tumor lysis syndrome as well as in a model of mitochondrial encephalopathy, FJ-C staining failed to detect neuronal death. Histopathologically, these models were characterized by extensive neuronal vacuolation associated with fading neurons ("ghost cells"). Therefore, contrary to the widespread belief that FJ-C stain has high affinity for all degenerating neurons regardless of the underlying cell death mechanism, we observed restricted sensitivity of the technique to specific conditions of neuronal cell death. As such, complementary techniques are essential to evaluate the presence of neurodegeneration in the absence of a positive FJ-C signal.


An integrative review of Reiki touch therapy research.
Reiki touch therapy is a complementary biofield energy therapy that involves the use of hands to help strengthen the body's ability to heal. There is growing interest among nurses to use Reiki in patient care and as a self-care treatment, however, with little supportive empirical research and evidence to substantiate these practices. The purpose of this integrative review is to begin the systematic process of evaluating the findings of published Reiki research. Selected investigations using Reiki for effects on stress, relaxation, depression, pain, and wound healing management, among others is reviewed and summarized. A summary of Reiki studies table illustrates the study descriptions and Reiki treatment protocols specified in the investigations. Synthesis of findings for clinical practice and implications for future research are explored.


Disruption of the kringle 1 domain of prothrombin leads to late onset mortality in zebrafish.
The ability to prevent blood loss in response to injury is a conserved function of all vertebrates. Complete deficiency of the central clotting enzyme prothrombin has never been observed in humans and is incompatible with postnatal life in mice, thus limiting the ability to study its role in vivo. Zebrafish are able to tolerate severe hemostatic deficiencies that are lethal in mammals. We have generated a targeted genetic deletion in the kringle 1 domain of zebrafish prothrombin. Homozygous mutant embryos develop normally into the mid-juvenile stage but demonstrate complete mortality by 2 months of age primarily due to internal hemorrhage. Mutants are unable to form occlusive venous and arterial thrombi in response to endothelial injury, a defect that was phenocopied using direct oral anticoagulants. Human prothrombin engineered with the equivalent mutation exhibits a severe reduction in secretion, thrombin generation, and fibrinogen cleavage. Together, these data demonstrate the conserved function of thrombin in zebrafish and provide insight into the role of kringle 1 in prothrombin maturation and activity. Understanding how zebrafish are able to develop normally and survive into early adulthood without thrombin activity will provide important insight into its pleiotropic functions as well as the management of patients with bleeding disorders.


Hydrogen Gas Treatment Improves the Neurological Outcome After Traumatic Brain Injury Via Increasing miR-21 Expression.
Hydrogen gas (H2) exerts a beneficial effect against traumatic brain injury (TBI). microRNA-21 (miR-21) is one of the most highly expressed members of small non-coding microRNA family in mammalian cells. miR-21 can improve the neurological outcome after TBI. In the present study, we investigated whether H2 treatment could improve the neurological outcome after TBI via increasing miR-21 expression. TBI was induced by controlled cortical impact in rats. H2 treatment was given by exposure to 2% H2 from 30 min to 5 h after TBI operation. Here, we found that H2 treatment significantly increased the expression of miR-21 in brain from 6 h to 3 d after TBI. The level of miR-21 expression in brain was significantly decreased after intracerebroventricular infusion of miR-21 antagomir in TBI-challenged rats with or without H2 treatment. Moreover, we found that H2 treatment conferred a better neurological outcome after TBI by improving neurological dysfunction, alleviating brain edema as well as decreasing lesion volume and blood-brain barrier permeability, which were significantly prevented by miR-21 antagomir. Furthermore, intracerebroventricular infusion of miR-21 agomir increased the level of miR-21 expression and decreased the lesion volume after TBI. In addition, H2 treatment decreased the levels of oxidative products (malondialdehyde and 8-iso-prostaglandin F2α) and increased the activities of endogenous antioxidant enzymes (superoxide dismutase and catalase) in brain after TBI, which were prevented by miR-21 antagomir. Taken together, these data indicate that H2 treatment improves the neurological outcome after TBI via increasing miR-21 expression.


An Insight into the Phase Transformation of WS2 upon Fluorination.
The transformation from semiconducting to metallic phase, accompanied by a structural transition in 2D transition metal dichalcogenides has attracted the attention of the researchers worldwide. The unconventional structural transformation of fluorinated WS2 (FWS2 ) into the 1T phase is described. The energy difference between the two phases debugs this transition, as fluorination enhances the stability of 1T FWS2 and makes it energetically favorable at higher F concentration. Investigation of the electronic and optical nature of FWS2 is supplemented by possible band structures and bandgap calculations. Magnetic centers in the 1T phase appear in FWS2 possibly due to the introduction of defect sites. A direct consequence of the phase transition and associated increase in interlayer spacing is a change in friction behavior. Friction force microscopy is used to determine this effect of functionalization accompanied phase transformation.


Organic Anion Transporting Polypeptide-Mediated Hepatic Uptake of Glucuronide Metabolites of Androgens.
We previously established that androgen glucuronides are effluxed by multidrug resistance-associated proteins 2 and 3. However, no data exist on the mechanism of hepatic uptake of these metabolites. The first goal of this study was to explore the role of hepatic uptake transporters and characterize transport kinetics of glucuronides of testosterone (TG), dihydrotestosterone (DHTG), androsterone (AG), and etiocholanolone (EtioG) using cell lines overexpressing organic anion transporting polypeptides (OATP1B1, OATP1B3, and OATP2B1). Using a quantitative proteomics-guided approach, we then estimated the fractional contribution of individual OATPs in hepatic uptake of these glucuronides. The transport screening assays revealed that the glucuronides were primarily taken up by OATP1B1 and OATP1B3. The K m values for OATP1B1-mediated uptake were low for EtioG (6.2 µM) as compared with AG, TG, and DHTG (46.2, 56.7, and 71.3 µM, respectively), whereas the K m value for OATP1B3-mediated uptake for EtioG, AG, DHTG, and TG were 19.8, 29.3, 69.6, and 110.4 µM, respectively. Both OATP1B1 and OATP1B3 exhibited the highest transport rate toward AG as compared with other glucuronides. When adjusted for the transporter abundance in human livers, EtioG and DHTG were predicted to be transported by both OATP1B1 and OATP1B3, whereas TG and AG were preferentially (>68%) transported by OATP1B3. Collectively, this report elucidates the mechanisms of hepatic uptake of androgen glucuronides. Perturbation of these processes by genetic polymorphisms, disease conditions, or drug interactions can lead to changes in enterohepatic recycling of androgens. TG and AG can be further investigated as potential biomarkers of OATP1B3 inhibition. SIGNIFICANCE STATEMENT: This is the first study to elucidate the mechanism of hepatic uptake of androgen glucuronides and estimate the fractional contribution of individual OATPs using quantitative proteomics. Our results show that both OATP1B1 and OATP1B3 are responsible for the hepatic uptake of major circulating testosterone glucuronides. The apparent higher selectivity of OATP1B3 toward testosterone glucuronide and androsterone glucuronide can be leveraged for establishing these metabolites as clinical biomarkers of OATP1B3 activity.


Use of two-dimensional electrophoresis To study differential protein expression in divercin V41-resistant and wild-type strains of Listeria monocytogenes.
The use of bacteriocins from food-grade lactic acid bacteria to fight against the food-borne pathogen Listeria monocytogenes has been gaining interest. However, the emergence of resistant cells is frequently reported when Listeria is exposed to such antibacterials. A two-dimensional electrophoresis study of whole-cell protein expression of Listeria monocytogenes variants sensitive or resistant to the action of a bacteriocin produced by Carnobacterium divergens V41, divercin V41, is reported in this paper. The resistant variant obtained from the sensitive strain of L. monocytogenes P was also resistant to piscicocins V1 and SF668, but remained sensitive to nisin. Its growth rate was 50% less than the sensitive strain, and the MIC for it was 10(4) times higher. No reversion of the resistance was observed after 20 successive cultures in the absence of divercin V41. Comparison of the protein patterns by two-dimensional gel electrophoresis analysis showed clear differences. In the resistant variant pattern, at least nine spots had disappeared and eight new ones were observed. One of the newly synthesized proteins was identified as a flagellin of L. monocytogenes. Direct interaction between flagellin and divercin V41 was not evidenced. Intracellular synthesis of flagellin is probably an indirect effect of a modification in transcriptional regulation with widespread effects through a sigma factor. An intense protein, only present in the sensitive strain, was identified as a non-heme iron-binding ferritin displaying strong similarities to Dps proteins. Common modifications in the transcriptional regulation for these two proteins are discussed.


[Bromocriptine monotherapy of a prolactinoma causing erectile dysfunction].
A case of erectile dysfunction in a patient with prolactinoma is described herein. The literature on the incidence, diagnosis and therapeutic management of this condition is reviewed. Impotence may arise from several causes. It is widely accepted that 30-50% have an organic etiology, with vascular involvement being more prevalent than other causes (neurological, endocrinological, urological, iatrogenic, pharmacological, systemic diseases). Hyperprolactinemia, arising from a prolactinoma, is one of the endocrinological conditions causing impotence. In men, this endocrinological disorder is rarely accompanied by other clinical anomalies, such as gynecomastia, galactorrhea or signs of a pituitary tumor. The patient described herein presented with erectile dysfunction. During evaluation, he was found to be hyperprolactinemic. Subsequent assessment disclosed a pituitary adenoma. The patient was successfully treated with bromocriptine. Erectile dysfunction arising from hyperprolactinemia is uncommon. Serum prolactin levels, a lateral skull x-ray and CT/MRI are essential in the diagnosis and treatment of this condition. Treatment must be directed at the underlying cause. Bromocriptine has proved to be effective and carries a low risk of undesired effects.


Production and characterization of a human recombinant monoclonal Fab fragment specific for influenza A viruses.
A human recombinant monoclonal Fab fragment that specifically recognizes all the influenza A virus strains tested was produced in transformed Escherichia coli using the phage display technique. No strain of influenza B virus reacted with it. It was purified after four cycles of panning and by a single passage through an immunoaffinity column. About 1 mg of pure monoclonal antibody was obtained from 1 liter of culture medium in 3 working days. The Fab fragment reacted with a viral 27-kDa protein, which could reasonably be a matrix protein. Indirect immunofluorescence tests performed on virus-infected MDCK cells showed that this Fab fragment was at least equally efficient as other commercial monoclonal antibody-based systems in detecting influenza A viral infections. The potential advantages of human recombinant Fabs on murine monoclonal antibodies are discussed.


Bacterial endocarditis after Hurst bougienage in a patient with a benign oesophageal stricture.
A case of bacterial endocarditis which proved fatal in a 65-year-old edentulous male Caucasian with rheumatic valvular heart disease is reported. This occurred following dilatation of a benign oesophageal stricture with a Hurst mercury bougie. Transient low grade bacteraemia following upper gastrointestinal intubation is well documented but we are not aware of any published reports on bacterial endocarditis following this procedure and the possible implications of this case are discussed.


Gandouling alleviates nerve injury through PI3K/Akt/FoxO1 and Sirt1/FoxO1 signaling pathway to inhibit autophagy in the rats model of Wilson's disease.
Previous studies have shown that Gandouling (GDL) may alleviate the nerve damage caused by Wilson's disease (WD) by inhibiting the autophagy of nerve cell mitochondria. However, its mechanisms are still unclear. Revealing the therapeutic mechanism of GDL is beneficial for its clinical application and provides theoretical support for the development of new formulations for treating WD. This time we found that the oxidative stress level in the body of the copper-overloaded WD rates increased, neurons in the hippocampus were damaged, and autophagy occurred. GDL reversed these situations and significantly improved the learning, memory, and spatial cognitive abilities of the high-copper-loaded WD rates. After GDL intervention, the expression of phosphatidylinositol-3 kinase (PI3K), phosphorylated serine-threonine protein kinase (AKT), and phosphorylated forkhead box protein O1 (FoxO1) significantly increased, whereas FoxO1 in the nucleus decreased and phosphorylated FoxO1 in the cytoplasm also significantly raised. In addition, the expression of Sirt1 significantly declined, and Ac-FoxO1 in the nucleus also significantly increased. These data indicated that GDL may promote the phosphorylation of FoxO1 and promote its nucleation by activating the PI3K/AKT/FoxO1 signaling pathway and inhibit Ac-FoxO1 hydrolysis in the nucleus through the Sirt1/FoxO1 signaling pathway to suppress the transcriptional activity of FoxO1. Furthermore, it inhibited the expression of autophagy genes Atg12 and Gabarapl1. In summary, our work provides new insights into the potential mechanisms of GDL repairing WD neuronal damage through autophagy pathways.


Pathology of hearts after aortocoronary saphenous vein bypass grafting for coronary artery disease, studied by post-mortem coronary angiography.
A detailed pathological study was made in 10 patients dying up to 13 months after aortocoronary saphenous vein bypass grafting for coronary atherosclerosis. The coronary arteries and vein grafts were investigated by injection with a radio-opaque mass, radiography, dissection, and histology. The report is to some extent historical since the patients died during a period when the operation was first being introduced into two cardiothoracic hospitals. About 80 operations were performed during the time the 10 deaths occurred, a mortality of 12-5 per cent (including cases followed up to 13 months after operation). Seven of the patients were operated on for intractable angina and 3 with a view to aneurysmectomy. All the patients selected for operation were severely disabled despite medical treatment. The main cause of death was extremely severe coronary artery disease and its effects on the left ventricle; in one case, over two-thirds of the left ventricle had been destroyed by infarction before operation. Other causes or contributing causes of death were pulmonary embolism, myocardial infarction complicating angiography (ostial stenosis), and cerebral damage. Ten of the 14 vein grafts (71%) were patent at necropsy. A free flow of injection medium usually occurred between patent grafts and coronary arteries. Thrombosis of a graft was thought to have contributed to death in 3 patients, but not in a fourth who died of pulmonary embolism. Since thrombosis of grafts was usually secondary to poor run-off blood into severely atheromatous coronary arteries, this was also an indirect effect of the advanced coronary arterial disease. In one case, thrombosis followed severe chronic intimal thickening of a graft in place for 13 months. The study of these deaths emphasizes that in some patients the pathological changes in the coronary arteries and left ventricle are too severe for them to benefit from surgery. Vein grafts cannot be expected to distribute blood effectively through grossly narrowed coronary arteries. In addition, when a large part of the left ventricle is infarcted or scarred, it is almost certain that improving the blood supply by grafting will not result in significant regeneration of cardiac muscle. Since the time when this study was made, there have been few deaths among the many vein graft operations subsequently carried out in the hospitals involved. The two most important factors thought responsible for the improvement are the selection of cases more suitable for surgery by continued improvement of diagnostic techniques, and also the employment of more radical surgical procedures in the form of coronary endarterectomy and the insertion of more grafts per patient.


Do photosynthetic bacteria contain cytochrome c1?
A method is described for characterizing, c-type cytochromes in bacterial membrane preparations according to molecular weight on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. Applied to the photosynthetic bacterium Rhodopseudomonas sphaeroides this technique is used, together with spectroscopic measurements, to demonstrate that a membrane-bound cytochrome c of mol.wt. 30000 is active in photosynthetic electron transport in addition to the well-known soluble cytochrome, cytochrome c2. The membrane cytochrome has a midpoint potential (E'0) at pH 7 of +290 mV, as compared with +360 mV for purified cytochrome c2. Its alpha-band has a peak near 552 nm, as compared with 550 nm for cytochrome c2. Evidence is presented that chromatophores contain roughly equal amounts of the two cytochromes.


Nuclear Receptor Nr4a1 Regulates Striatal Striosome Development and Dopamine D1 Receptor Signaling.
The GABAergic medium-size spiny neuron (MSN), the striatal output neuron, may be classified into striosome, also known as patch, and matrix, based on neurochemical differences between the two compartments. At this time, little is known regarding the regulation of the development of the two compartments. Nr4a1, primarily described as a nuclear receptor/immediate early gene involved in the homeostasis of the dopaminergic system, is a striosomal marker. Using Nr4a1-overexpressing and Nr4a1-null mice, we sought to determine whether Nr4a1 is necessary and/or sufficient for striosome development. We report that in vivo and in vitro, Nr4a1 and Oprm1 mRNA levels are correlated. In the absence of Nr4a, there is a decrease in the percentage of striatal surface area occupied by striosomes. Alterations in Nr4a1 expression leads to dysregulation of multiple mRNAs of members of the dopamine receptor D1 signal transduction system. Constitutive overexpression of Nr4a1 decreases both the induction of phosphorylation of ERK after a single cocaine exposure and locomotor sensitization following chronic cocaine exposure. Nr4a1 overexpression increases MSN excitability but reduces MSN long-term potentiation. In the resting state, type 5 adenylyl cyclase (AC5) activity is normal, but the ability of AC5 to be activated by Drd1 G-protein-coupled receptor inputs is decreased. Our results support a role for Nr4a1 in determination of striatal patch/matrix structure and in regulation of dopaminoceptive neuronal function.


Effect of diet protein restriction on progression of chronic kidney disease: A systematic review and meta-analysis.
Dietary protein restriction has long been thought to play an important role in the progression of chronic kidney disease (CKD); however, the effect of dietary protein on the rate of decline in kidney function remains controversial. We undertook a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the influence of protein restriction on chronic kidney disease. Ovid MEDLINE (from 1946 to March 5, 2016), EMBASE (from 1966 to March 5, 2016), and the Cochrane Library (Inception to March 5, 2016) were searched to identify RCTs comparing different levels of protein intake for at least 24 weeks in adult patients with CKD. The outcomes included kidney failure events, the rate of change in estimated glomerular filtration rate (eGFR) per year, all cause death events, and changes in proteinuria, serum phosphorus concentration, serum albumin, and body mass index (BMI). Nineteen trials with 2492 subjects were analyzed. A low protein diet reduced the risk of kidney failure (odds ratio (OR) = 0.59, 95% CI: 0.41 to 0.85) and end-stage renal disease (ESRD) (OR = 0.64, 95% CI: 0.43 to 0.96), but did not produce a clear beneficial effect for all cause death events (OR = 1.17, 95% CI: 0.67 to 2.06). The change in the mean difference (MD) for the rate of decline in the eGFR was significant (MD: -1.85, P = 0.001), and for proteinuria (MD: -0.44, P = 0.02). A low protein diet also reduced the serum phosphorus concentration (MD: -0.37, 95% CI: -0.5 to -0.24) and BMI (MD: -0.61, 95% CI: -1.05 to -0.17). However the change in albumin presented no significant difference between two groups (MD: 0.23, 95% CI: -0.51 to 0.97). Based on the findings of our meta-analysis, protein-restricted diet may reduce the rate of decline in renal function and the risk of kidney failure for CKD populations, but did not produce a clear beneficial effect for all cause death events. Besides However, the optimal level of protein intake in different participants is left unanswered, and the nutritional status should be regarded with caution.


The impact of beyondblue: the national depression initiative on the Australian public's recognition of depression and beliefs about treatments.
To evaluate whether a campaign to increase public knowledge about depression (beyondblue: the national depression initiative) has influenced the Australian public's ability to recognize depression and their beliefs about treatments. Data from national surveys of mental health literacy in 1995 and 2003-04 were analysed to see if states and territories which funded beyondblue (the high exposure states) had greater change than those that did not (the low exposure states). In both surveys, participants were asked what was wrong with a person in a depression case vignette and to give opinions about the likely helpfulness for this person of a range of treatments. In the 2003-04 survey participants were also asked questions to assess awareness of beyondblue. Awareness of beyondblue in the states that provided funding was found to be around twice the level of those that did not. Using the low-exposure states as a control, the high-exposure states had greater change in beliefs about some treatments, particularly counselling and medication, and about the benefits of help-seeking in general. Recognition of depression improved greatly at a national level, but slightly more so in the high-exposure states. The data are consistent with beyondblue having had a positive effect on some beliefs about depression treatment.


[Epidemiology of tuberculosis in Moscow].
Tuberculous infection is no longer controllable in Moscow. Tuberculosis ranks first in the structure of morbidity caused by monoinfections. The prevalence of tuberculosis is increasing both among adults and children. Increasing incidence of forms with bacterial release is especially dangerous. Such patients represent the greatest epidemic hazard for the population. In Moscow the situation with tuberculosis is characterized by a notable reservoir of infection among socially maladapted subjects. A special department for this patient population was created in tuberculosis hospital No. 11; besides medical care, the patients are rendered social care there. The situation with tuberculosis in Russia and in Moscow requires urgent measures aimed at stabilization of the epidemiological process.


Frequency-dependent changes in cerebral metabolic rate of oxygen during activation of human visual cortex.
To test the hypothesis that brain oxidative metabolism is significantly increased upon adequate stimulation, we varied the presentation of a visual stimulus to determine the frequency at which the metabolic response would be at maximum. The authors measured regional CMR(O2) in 12 healthy normal volunteers with the ECAT EXACT HR+ (CTI/Siemens, Knoxville, TN, U.S.A.) three-dimensional whole-body positron emission tomograph (PET). In seven successive activating conditions, subjects viewed a yellow-blue annular checkerboard reversing its contrast at frequencies of 0, 1, 4, 8, 16, 32, and 50 Hz. Stimulation began 4 minutes before and continued throughout the 3-minute dynamic scan. In the baseline condition, the subjects began fixating a cross hair 30 seconds before the scan and continued to do so for the duration of the 3-minute scan. At the start of each scan, the subjects inhaled 20 mCi of (15)O-O2 in a single breath. The CMR(O2) value was calculated using a two-compartment, weighted integration method. Normalized PET images were averaged across subjects and coregistered with the subjects' magnetic resonance imaging in stereotaxic space. Mean subtracted image volumes (activation minus baseline) of CMR(O2) then were obtained and converted to z statistic volumes. The authors found a statistically significant focal change of CMR(O2) in the striate cortex (x = 9; y = -89; z = -1) that reached a maximum at 4 Hz and dropped off sharply at higher stimulus frequencies.


Role of cytochrome B5 in modulating peroxide-supported cyp3a4 activity: evidence for a conformational transition and cytochrome P450 heterogeneity.
The role of cytochrome b(5) (b(5)) in the alpha-naphthoflavone (alpha-NF)-mediated inhibition of H(2)O(2)-supported 7-benzyloxyquinoline (7-BQ) debenzylation by heterologously expressed and purified cytochrome P450 3A4 (CYP3A4) was studied. Although alpha-NF showed negligible effect in an NADPH-dependent reconstituted system, inhibition of 7-BQ oxidation was observed in the H(2)O(2) system. Analysis of the effect of various constituents of a standard reconstituted system on H(2)O(2)-supported activity showed that b(5) alone resulted in a 2.5-fold increase in the k(cat) value and reversed the inhibitory effect of alpha-NF. In addition, titration with b(5) suggested that only 65% of the CYP3A4 participated in the interaction with b(5), consistent with cytochrome P450 (P450) heterogeneity. Study of the influence of b(5) on the kinetics of H(2)O(2)-dependent destruction of the P450 heme moiety suggested two distinct conformers of CYP3A4 with different sensitivity to heme loss. In the absence of b(5), 66% of the wild-type enzyme was bleached in the fast phase, whereas the addition of b(5) decreased the fraction of the fast phase to 16%. Finally, to locate amino acid residues that might influence b(5) action, several active site mutants were tested. Substitution of Ser-119, Ile-301, Ala-305, Ile-369, or Ala-370 with the larger Phe or Trp decreased or even abolished the activation by b(5). Ser-119 is in the B'-C loop, a predicted b(5)-P450 interaction site, and Ile-301 and Ala-305 are closest to the heme. In conclusion, the interaction of b(5) with P450 apparently leads to a conformational transition, which results in redistribution of the CYP3A4 pool.


Dominant trait linked to chromosome 1 in DBA/2 mice for the resistance to autoimmune gastritis appears in bone marrow cells.
Neonatal thymectomy (NTx) induces autoimmune gastritis (AIG) in BALB/c mice, a model for human type A chronic atrophic gastritis, but not in DBA/2 mice and rarely in CDF1 mice (a hybrid of BALB/c and DBA/2 mice). The aim of this study was to clarify the mechanisms of AIG-resistance in mice bearing the dominant trait of DBA/2. Linkage groups associated with, and cells related to AIG resistance were examined with CDF1-BALB/c backcrosses. Intracellular staining and flow-cytometric bead array for several cytokines were performed on NTx BALB/c mice and NTx DBA/2-chimeric BALB/c mice receiving DBA/2-bone marrow cells. In NTx BALB/c mice, IFN-γ-secreting CD4(+) T cells were increased, but not in NTx DBA/2 mice. Because Vβ6(+) T cell-bearing mice of half of their backcrosses developed AIG, but the other half of Vβ6(+) T cell-negative mice developed scarcely, resistance for AIG generation is associated with the presence of the Mls-1a locus on chromosome 1 in DBA/2 mice, which deletes Vβ6(+) T cells. NTx DBA/2-chimera BALB/c mice showed dominant production of IL-10 and resistance for AIG, although the deletion of Vβ6(+) T cells was found not to be a cause of AIG-resistance from Mls-1a locus segregation experiments. Although NTx DBA/2-chimeric BALB/c mice did not suffer from AIG, they brought immediate precursors of T cells for AIG. It is concluded that DBA/2 mice generate bone marrow-derived cells that produce anti-inflammatory cytokines to prevent the activation of AIG-T cells.


[Leather bags production: organization study, general identification of hazards, biomechanical overload risk pre-evaluation using an easily applied evaluation tool].
Craft industries are the backbone of the Italian manufacturing system and in this sector the leather trade plays a crucial role. The aim of the study was to experiment with a risk pre-mapping data sheet in leather bag manufacture by analyzing the production cycle. The prevalence of biomechanical, organizational and physical factors was demonstrated in tanneries. With regard to chemical agents the lack of any priority of intervention could be due to the lack of information on the chemicals used. In the 2 enterprises that used mechanical processes the results showed different priorities for intervention and a different level of the extent of such intervention. In particular in the first enterprise biomechanical overload was a top priority, while in the second the results were very similar to those of the tannery. The analysis showed in both companies that there was a high prevalence of risk of upper limb biomechanical overload in leather bag manufacture. Chemical risk assessment was not shown as a priority because the list of chemicals used was neither complete nor sufficient. The risk pre-mapping data sheet allowed us to obtain a preliminary overview of all the major existing risks in the leather industry. Therefore the method can prove a useful tool for employers as it permits instant identification of priorities for intervention for the different risks.


Behavioral drive versus behavioral inertia in evolution: a null model approach.
Some biologists embrace the classical view that changes in behavior inevitably initiate or drive evolutionary changes in other traits, yet others note that behavior sometimes inhibits evolutionary changes. Here we develop a null model that quantifies the impact of regulatory behaviors (specifically, thermoregulatory behaviors) on body temperature and on performance of ectotherms. We apply the model to data on a lizard (Anolis cristatellus) and show that thermoregulatory behaviors likely inhibit selection for evolutionary shifts in thermal physiology with altitude. Because behavioral adjustments are commonly used by ectotherms to regulate physiological performance, regulatory behaviors should generally constrain rather than drive evolution, a phenomenon we call the "Bogert effect." We briefly review a few other examples that contradict the classical view of behavior as the inevitable driving force in evolution. Overall, our analysis and brief review challenge the classical view that behavior is invariably the driving force in evolution, and instead our work supports the alternative view that behavior has diverse--and sometimes conflicting--effects on the directions and rates at which other traits evolve.


Photosynthetic responses of Halimeda scabra (Chlorophyta, Bryopsidales) to interactive effects of temperature, pH, and nutrients and its carbon pathways.
In this study, we evaluated the interactive effects of temperature, pH, and nutrients on photosynthetic performance in the calcareous tropical macroalga Halimeda scabra. A significant interaction among these factors on gross photosynthesis (Pgross ) was found. The highest values of Pgross were reached at the highest temperature, pH, and nutrient enrichment tested and similarly in the control treatment (no added nutrients) at 33 °C at the lowest pH. The Q 10 Pgross values confirmed the effect of temperature only under nutrient enrichment scenarios. Besides the above, bicarbonate (HCO3 -) absorption was assessed by the content of carbon stable isotope (δ13C) in algae tissue and by its incorporation into photosynthetic products, as well as by carbonic anhydrase (CA) inhibitors (Acetazolamide, AZ and Ethoxyzolamide, EZ) assays. The labeling of δ13C revealed this species uses both, CO2 and HCO3 - forms of Ci relying on a CO2 Concentration Mechanism (CCM). These results were validated by the EZ-AZ inhibition assays in which photosynthesis inhibition was observed, indicating the action of internal CA, whereas AZ inhibitor did not affect maximum photosynthesis (Pmax ). The incorporation of 13C isotope into aspartate in light and dark treatments also confirmed photosynthetic and non-photosynthetic the HCO3 -uptake.


Practical Guidelines on Implementing Hypofractionated Radiotherapy for Prostate Cancer in Africa.
Among a growing body of literature in global oncology, several articles project increased cost savings and radiotherapy access by adopting hypofractionated radiotherapy (HFRT) in low- and middle-income countries (LMICs) like those in Africa. Clinical trials in Europe and the USA have demonstrated HFRT to be non-inferior to conventional radiotherapy for eligible patients with several cancers, including prostate cancer. This could be a highly recommended option to battle a severely large and growing cancer burden in resource-limited regions. However, a level of implementation research may be needed in limited resource-settings like in Africa. In this article, we present a list of evidence-based recommendations to practice HFRT on eligible prostate cancer patients. As literature on HFRT is still developing, these guidelines were compiled from review of several clinical trials and professionally accredited material with minimal resource requirements in mind. HFRT guidelines presented here include patient eligibility, prescription dose schedules, treatment planning and delivery techniques, and quality assurance procedures. The article provides recommendations for both moderately hypofractionated (2.4-3.4Gy per fraction) and ultrahypofractionated (5Gy or more per fraction) radiation therapy when administered by 3D-Conformal Radiotherapy, Intensity Modulated Radiation Therapy, or Image-Guided Radiotherapy. In each case radiation oncology health professionals must make the ultimate judgment to ensure safety as more LMIC centers adopt HFRT to combat the growing scourge of cancer.


Appropriate head position for nasotracheal intubation by using lightwand device (Trachlight).
The purpose of this study was to determine the relationship between the head position and the subsequent ease of nasotracheal intubation by using the lightwand device Trachlight (TL). Patients requiring nasotracheal intubation were subdivided into 3 groups according to the intubated head position (group S: sniffing position; group E: extension position; and group N: neutral position). The number of attempts, the total intubation time, and the failures of the TL intubation were recorded. Intubation difficulty by means of TL was assessed by the ordinal 6-point scale. Of the 300 patients enrolled in the study, TL intubation was successful in 91.3% of them. There was no significant difference in the success rate of the first attempt between the groups. No correlation between the ordinal scale and the head position was observed. The total intubation time and the ratio of "unsuccessful" cases were not significantly different among the 3 groups. TL is an effective alternative for patients who require nasotracheal intubation. Our study did not determine the most favorable head position for nasotracheal intubation with the TL, so we recommend that nasotracheal intubation with TL be started with the head in the neutral position and then changed to a more appropriate position, if necessary, on an individual basis.


Factors explaining limitations in activities and restrictions in participation in rheumatoid arthritis.
The objectives of this study were to examine which factors, according to the International Classification of Functioning, Disability and Health (ICF) framework contribute to the explanation of activity limitations measured by the Health Assessment Questionnaire (HAQ - model I) and which factors contribute to the explanation of participation restrictions measured by the Social Function Scale of SF-36 (model II) in patients with rheumatoid arthritis (RA). Cross-sectional data collection of variables concerning the health status of 239 consecutively included patients with RA at the outpatient Departments of Physical Medicine and Rehabilitation of the University Hospital of Zurich and of the University Hospital of Munich was conducted. Measures included: disease activity score (DAS-28), Rheumatoid Arthritis Disease Activity Index (RADAI), HAQ, Short-form-36 (SF-36), Sociodemo-graphy Questionnaire, Comorbidity Questionnaire (SCQ), Muscle Strength Index (MSI), range of motion (EPM-ROM), grip strength, Sequentional Occupational and Dexterity Assessment (SODA), radiologic score (Ratingen Score). Multivariate regression analyses were conducted building models of explanation. Model I included vitality, RADAI, DAS, SODA PAIN Score, MSI and EPM-ROM as explaining variables with a globally explained variance of 53%. Model II included vitality, mental health, the HAQ and living alone as explaining variables with a globally explained variance of 42.4%. Activity limitations in RA were mainly explained by vitality and disease activity factors. Restrictions in participation in RA were mainly explained by vitality and mental health.


Evaluation of the Long-Term Cost-Effectiveness of the Dexcom G6 Continuous Glucose Monitor versus Self-Monitoring of Blood Glucose in People with Type 1 Diabetes in Canada.
The Dexcom G6 real-time continuous glucose monitoring (RT-CGM) system is one of the most sophisticated RT-CGM systems developed to date and became available in Canada in 2019. A health economic analysis was performed to determine the long-term cost-effectiveness of the Dexcom G6 RT-CGM system versus SMBG in adults with type 1 diabetes (T1D) in Canada. The analysis was performed using the IQVIA Core Diabetes Model. Based on clinical trial data, patients with mean baseline HbA1c of 8.6% were assumed to have a HbA1c reduction of 1.0% with RT-CGM versus 0.4% reduction with SMBG. RT-CGM was also associated with a quality of life (QoL) benefit owing to reduced incidence of hypoglycemia, reduced fear of hypoglycemia (FoH) and elimination of fingerstick testing. Direct medical costs were sourced from published literature, and inflated to 2019 Canadian dollars (CAD). Dexcom G6 RT-CGM was projected to improve mean quality-adjusted life expectancy by 2.09 quality-adjusted life years (QALYs) relative to SMBG (15.52 versus 13.43 QALYs) but mean total lifetime cots were CAD 35,353 higher with RT-CGM (CAD 227,357 versus CAD 192,004) resulting in an incremental cost-effectiveness ratio (ICER) of CAD 16,931 per QALY gained. Sensitivity analyses revealed that assumptions relating to the QoL benefit associated with reduced FoH and the elimination of fingerstick testing with RT-CGM as well as SMBG usage and change in HbA1c were the key drivers of cost-effectiveness. For adults with T1D in Canada, RT-CGM is associated with improved glycemic control and QoL benefits owing to a reduced FoH and elimination of the requirement for fingerstick testing and over a lifetime time horizon is cost-effective relative to SMBG.


Liver transplantation for intrahepatic cholangiocarcinoma.
Although hepatocellular carcinoma (HCC) has become a common indication for liver transplantation (LT), intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) are historically contraindicated due to their aggressive behavior. On the basis of recent experiences, some groups have proposed a clinical trial investigating the role of LT for patients with early cholangiocarcinoma (CCA), defined as a single lesion ≤ 2 cm. The purpose of this study is to assess the clinicopathologic features and outcomes following LT for patients who were initially diagnosed with HCC and subsequently found to have either ICC or cHCC-CCA on explant. Patients with the diagnosis of primary liver cancer (PLC) after LT from a single center were retrospectively reviewed. Outcomes for patients with early CCA were compared with patients with HCC within Milan criteria (MC). Out of 618 patients transplanted with PLC, 44 patients were found to have CCA on explant. On the basis of preoperative imaging, 12 patients met criteria for early CCA and were compared with 319 patients who had HCC within MC. The 1- and 5-year overall survival for early CCA versus HCC was 63.6% versus 90.0% and 63.6% versus 70.3% (log-rank, P = 0.25), respectively. Overall recurrence was 33.3% for early CCA versus 11% for HCC. On explant the patients with CCA were more likely understaged with higher tumor grade and vascular invasion. In conclusion, patients with CCA present a diagnostic challenge, which often leads to the finding of more aggressive lesions on explant after LT, higher recurrence rates, and worse post-LT survival. Careful consideration of this diagnostic conundrum needs to be made before a clinical trial is undertaken. Liver Transplantation 24 634-644 2018 AASLD.


Role of serotonin and dopamine receptor binding in antipsychotic efficacy.
In an effort to analyse the contribution of individual serotonin and dopamine receptor subtypes to antipsychotic medication response, we analysed the correlation between clinically effective antipsychotic drug dose and binding affinity to cloned serotonin and dopamine receptor subtypes. Clinically effective dosage and binding affinity to the D(2) dopamine receptor subtype were moderately correlated for typical antipsychotic medications (r=0.57, p=0.04), and were similarly modestly correlated for atypical antipsychotic drugs (r=0.66, p=0.07). Surprisingly for typical antipsychotic medications, a stronger inverse correlation was observed between drug dosage and 5-HT(2C) affinity (r=-0.65, p=0.03). The strongest correlation observed for typical antipsychotic medications was between medication dose and 5-HT(2C)/D(2) binding affinity ratio (r=-0.81, p=0.002). For atypical antipsychotic medications, highly significant correlations were observed between medication dose and receptor-binding affinity to D(3) dopamine receptor (r=0.78, p=0.02), and with the ratios of D(2)/5-HT(1A) (r=0.85, p=0.009), D(3)/5-HT(1A) (r=0.78, p=0.021), D(2) (5-HT(2A)/5-HT(1A)) (r=0.75, p=0.033) and D(3) (5-HT(2A)/5-HT(1A)) (r=0.75, p=0.03) receptor-binding affinities. The correlation between medication dose and D(2) (5-HT(2C)/5-HT(1A)) receptor-binding affinity ratio was of similar magnitude (r=0.70, p=0.055). No significant correlations were identified between atypical antipsychotic medication dose and 5-HT(1A), 5-HT(2A), 5-HT(2C), 5-HT(2C)/D(2) or 5-HT(2A)/D(2) receptor-binding affinities. These observations suggest an interaction between D(2) and 5-HT(2C) receptor-binding effects contributing to the therapeutic response achieved following treatment with typical antipsychotic medications. This suggests that for typical antipsychotic medications, constitutive serotonin 5-HT(2C) receptor signalling interacts with and facilitates the antipsychotic benefit achieved through dopamine D(2) receptor blockade. Additionally, this analysis demonstrates that, in contrast to typical antipsychotic medications, the therapeutic effectiveness of atypical antipsychotic medications results from opposing interactions among three distinct domains: (1) antipsychotic potency is enhanced by increased D(2) and D(3) dopamine receptor-binding affinity; (2) antipsychotic efficacy is also facilitated by increased binding affinity to serotonin 5-HT(2C) and 5-HT(2A) receptors; (3) in contrast, antipsychotic potency is reduced by elevations in 5-HT(1A) receptor-binding affinity.


Public health in central and eastern Europe and the role of environmental pollution.
The central and eastern European countries that composed the former Eastern Bloc have experienced an alarming decline in public health since the dissolution of the Soviet Union. Death rates have increased in most age groups. Life expectancy, especially among males, has decreased in many countries; in Russia, male life expectancy dropped by six years between 1989 and 1994. By 2020, these countries are projected to have smaller increases in life expectancy than any other geographic region. The conditions responsible for the excess mortality are cardiovascular disease, cancer, and injuries among adults. The major factors in the sharp increase are poverty, social disintegration, and crime, overlaid on historically high rates of smoking, alcohol use, and psychosocial stress. Environmental pollution, although common and sometimes severe in the former Eastern Bloc, is another, albeit not the chief, cause of the sharp decline in public health since 1989.


Genetic analysis of age at first service, return rate, litter size, and weaning-to-first service interval of gilts and sows.
The aim of this study was to estimate genetic parameters of seven traits related to sow reproductive performance. Data on all Norwegian Landrace pigs (NL) born in nucleus herds and raised in nucleus or multiplying herds from 1990 to 2000 were extracted from the Norwegian national recording scheme. Reproductive traits investigated were age at first service (AFS), return rate in gilts (RRg), age at first farrowing (AFF), live-born piglets in the first litter (NBA1), interval from weaning to first service after first litter (WTS1), return rate after first litter (RR1), live-born piglets in the second litter (NBA2), and interval from weaning to first service after second litter (WTS2). After editing, the data set comprised 12,583 to 56,042 records, depending on the trait. A mixed linear and a joint linear threshold animal model were used to estimate (co)variance components. A full Bayesian approach via Gibbs sampling was adopted. The statistical model used for analysis included contemporary groups of herd-year (-season), purebred or crossbred litter, single or double insemination, mating type, parity in which the animal was born, a regression on lactation length, and an additive genetic effect. Neither the estimated heritabilities nor the genetic correlations differed much between the two approaches, but there was a tendency for higher genetic correlations using the joint linear threshold model approach. Average heritabilities were as follows: AFS = 0.31; RRg = 0.03; RR1 = 0.02; NBA1 = 0.12; NBA2 = 0.14; WTS1 = 0.08; and WTS2 = 0.03. The highest genetic correlations were estimated between NBA1 and NBA2 (r(g) = 0.95), RR1 and WTS1 (r(g) = 0.93), and between WTS1 and WTS2 (r(g) = 0.78). The estimated genetic correlation between NBA and WTS were close to zero. Selection for increased NBA will slightly increase AFS and reduce the probability of a return. Selection for decreased AFS will have a favorable effect on WTS intervals; however, selection for decreased AFS seems to have an unfavorable effect on return rate both on gilts and sows. Conversely, selection for decreased WTS intervals will reduce the probability of a return. Potential selection candidates to include in a multivariate fertility index are AFS, NBA, and WTS1. Due to the low heritability and low, but favorable, genetic correlations to NBA and WTS, RR is not recommended as a selection candidate.


Needle-stick injuries in the National Health Service: a culture of silence.
Injury by contaminated sharp instruments and needles constitutes a major occupational hazard for healthcare workers. In a confidential survey at a district general hospital, 300 healthcare professionals were asked about their personal experience of needle-stick injury and their attitudes to reporting. 279 individuals responded, of whom 38% had experienced at least one needle-stick (mean 1.8) in the past year and 74% had sustained such an injury during their careers (mean 3.0). Although 80% of respondents were aware that such incidents should be notified, only 51% of those affected had reported all needle-stick injuries. Doctors were less likely to report than nurses, despite a higher liability to injury. This survey adds to evidence of a culture of silence pertaining to needle-stick injuries. The consequent risks to health, and the ethical and financial implications, remain uncertain.


rgs-CaM Detects and Counteracts Viral RNA Silencing Suppressors in Plant Immune Priming.
Primary infection of a plant with a pathogen that causes high accumulation of salicylic acid in the plant typically via a hypersensitive response confers enhanced resistance against secondary infection with a broad spectrum of pathogens, including viruses. This phenomenon is called systemic acquired resistance (SAR), which is a plant priming for adaption to repeated biotic stress. However, the molecular mechanisms of SAR-mediated enhanced inhibition, especially of virus infection, remain unclear. Here, we show that SAR against cucumber mosaic virus (CMV) in tobacco plants (Nicotiana tabacum) involves a calmodulin-like protein, rgs-CaM. We previously reported the antiviral function of rgs-CaM, which binds to and directs degradation of viral RNA silencing suppressors (RSSs), including CMV 2b, via autophagy. We found that rgs-CaM-mediated immunity is ineffective against CMV infection in normally growing tobacco plants but is activated as a result of SAR induction via salicylic acid signaling. We then analyzed the effect of overexpression of rgs-CaM on salicylic acid signaling. Overexpressed and ectopically expressed rgs-CaM induced defense reactions, including cell death, generation of reactive oxygen species, and salicylic acid signaling. Further analysis using a combination of the salicylic acid analogue benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH) and the Ca2+ ionophore A23187 revealed that rgs-CaM functions as an immune receptor that induces salicylic acid signaling by simultaneously perceiving both viral RSS and Ca2+ influx as infection cues, implying its autoactivation. Thus, secondary infection of SAR-induced tobacco plants with CMV seems to be effectively inhibited through 2b recognition and degradation by rgs-CaM, leading to reinforcement of antiviral RNA silencing and other salicylic acid-mediated antiviral responses.IMPORTANCE Even without an acquired immune system like that in vertebrates, plants show enhanced whole-plant resistance against secondary infection with pathogens; this so-called systemic acquired resistance (SAR) has been known for more than half a century and continues to be extensively studied. SAR-induced plants strongly and rapidly express a number of antibiotics and pathogenesis-related proteins targeted against secondary infection, which can account for enhanced resistance against bacterial and fungal pathogens but are not thought to control viral infection. This study showed that enhanced resistance against cucumber mosaic virus is caused by a tobacco calmodulin-like protein, rgs-CaM, which detects and counteracts the major viral virulence factor (RNA silencing suppressor) after SAR induction. rgs-CaM-mediated SAR illustrates the growth versus defense trade-off in plants, as it targets the major virulence factor only under specific biotic stress conditions, thus avoiding the cost of constitutive activation while reducing the damage from virus infection.


Inhibitor of apoptosis proteins as therapeutic targets in multiple myeloma.
The inhibitor of apoptosis (IAP) proteins have a critical role in the control of apoptotic machinery, and has been explored as a therapeutic target. Here, we have examined the functional importance of IAPs in multiple myeloma (MM) by using a Smac (second mitochondria-derived activator of caspases)-mimetic LCL161. We observed that LCL161 was able to potently induce apoptosis in some MM cell lines but not in others. Examining the levels of X-linked inhibitor of apoptosis protein (XIAP), cellular inhibitor of apoptosis protein 1 (cIAP1) and cellular inhibitor of apoptosis protein 2 (cIAP2) post LCL161 treatment indicated clear downregulation of both XIAP activity and cIAP1 levels in both the sensitive and less sensitive (resistant) cell lines. cIAP2, however, was not downregulated in the cell line resistant to the drug. Small interfering RNA-mediated silencing of cIAP2 significantly enhanced the effect of LCL161, indicating the importance of downregulation of all IAPs simultaneously for induction of apoptosis in MM cells. LCL161 induced marked up regulation of the Jak2/Stat3 pathway in the resistant MM cell lines. Combining LCL161 with a Jak2-specific inhibitor resulted in synergistic cell death in MM cell lines and patient cells. In addition, combining LCL161 with death-inducing ligands clearly showed that LCL161 sensitized MM cells to both Fas-ligand and TRAIL.


Soft tissue foreign body removal technique using portable ultrasonography.
Retained foreign objects account for as much as 2% of soft tissue injuries sustained in the wilderness. Subcutaneously embedded fragments are often missed during the initial medical evaluation and may result in morbidity secondary to delayed removal. Although the utility of ultrasonography in the emergency department for the detection of retained objects is established, the potential use of point-of-care ultrasound to aid with foreign body removal in the field has not been well described. We present 2 case reports that demonstrate the value of ultrasonography in detecting and successfully removing foreign bodies sustained in the wilderness, and outline a procedural technique that minimizes morbidity and uses equipment available in wilderness medical field kits. We propose that with the advent of portable and handheld ultrasound units, foreign body removal in the field has become feasible and may decrease the morbidity of soft tissue injuries, particularly in austere and wilderness environments with limited access to immediate medical care.


Cost-Effectiveness of Prefusion F Protein-Based Vaccines Against Respiratory Syncytial Virus Disease for Older Adults in the United States.
Two prefusion F protein-based vaccines, Arexvy and Abrysvo, have been authorized by the US Food and Drug Administration for protecting older adults against Respiratory Syncytial Virus (RSV)-associated lower respiratory tract illness. We evaluated the health benefits and cost-effectiveness of these vaccines. We developed a discrete-event simulation model, parameterized with the burden of RSV disease including outpatient care, hospitalization, and death for adults aged 60 years or older in the US. Taking into account the costs associated with these RSV-related outcomes, we calculated the net monetary benefit using quality-adjusted life-years (QALY) gained as a measure of effectiveness, and determined the range of price-per-dose (PPD) for Arexvy and Abrysvo vaccination programs to be cost-effective from a societal perspective. Using a willingness-to-pay of $95,000 per QALY gained, we found that vaccination programs could be cost-effective for a PPD under $120 with Arexvy and $111 with Abrysvo over the first RSV season. Achieving an influenza-like vaccination coverage of 66% for the population of older adults in the US, the budget impact of these programs at the maximum PPD ranged from $5.74 to $6.10 billion. If the benefits of vaccination extend to a second RSV season as reported in clinical trials, we estimated a maximum PPD of $250 for Arexvy and $233 for Abrysvo, with two-year budget impacts of $11.59 and $10.89 billion, respectively. Vaccination of older adults would provide substantial direct health benefits by reducing outcomes associated with RSV-related illness in this population.


[Clinical reasoning and decision-making in practice. A man with jaundice, renal function disorder, thrombocytopenia, muscular pain and confusion].
A 51-year-old man became jaundiced, after experiencing flu-like symptoms for a week. On admission anaemia, thrombocytopenia, and hepatic and renal function disorders were present. One month previously he had had sinusitis. Thrombotic thrombocytopenic purpura (TTP)/haemolitic-uraemic syndrome (HUS) was suspected, but the thrombocyte count rose spontaneously. The leukocytosis indicated an infectious cause of the symptoms and the jaundice appeared to originate from intrahepatic cholestasis. All symptoms could be traced to leptospirosis icterohaemorrhagica (known as 'Weil's disease'). The source was possibly the patient's fishpond. He recovered spontaneously and was also treated with antibiotics. Leptospirosis, a multi-organ disease is seen ever more infrequently as an occupational disease in stock farmers and increasingly frequently in people whose hobbies involved animals.


cobB function is required for catabolism of propionate in Salmonella typhimurium LT2: evidence for existence of a substitute function for CobB within the 1,2-propanediol utilization (pdu) operon.
The cobB function of Salmonella typhimurium LT2 was defined in vivo as an alternative activity for the nicotinic acid mononucleotide:5,6-dimethylbenzimidazole phosphoribosyltransferase enzyme (CobT), which is involved in the assembly of the nucleotide loop of cobalamin in this bacterium (J. R. Trzebiatowski, G. A. O'Toole, and J. C. Escalante-Semerena, J. Bacteriol. 176:3568-3575, 1994). In this paper we document that, independent of their inability to substitute for CobT function, cobB mutants are unable to use propionate as a carbon and energy source. A plasmid carrying only a wild-type copy of cobB complemented the cobalamin biosynthesis and propionate catabolism phenotypes of cobB mutants, indicating that a lack of CobB was responsible for both phenotypes. We demonstrate the existence of a function encoded by the 1,2-propanediol utilization (pdu) operon, which when induced by 1,2-propanediol compensated for the lack of CobB during propionate catabolism but failed to compensate for CobT in the assembly of the nucleotide loop of cobalamin in a cobB cobT double mutant.


Endothelial dysfunction and low grade chronic inflammation in subclinical hypothyroidism due to autoimmune thyroiditis.
The relationship between subclinical hypothyroidism (SH) and cardiovascular disease has been one of the most popular topics recently. There is still some controversy concerning its cardiovascular impact and management protocols. Our study aims to investigate the presence of the well known preceding clinical situations of atherosclerosis like endothelial dysfunction and inflammation in subclinical hypothyroidism. Thirty-seven patients with subclinical hypothyroidism (29 women, 8 men) and 23 healthy volunteers (19 women, 4 men) were recruited for the study. Endothelial dysfunction was measured by examining brachial artery responses to endothelium-dependent (flow mediated dilation, FMD) and endothelium-independent stimuli (sublingual nitroglycerin (NTG)). Serum TNF-alpha, interleukin-6, and hs-CRP were measured. The estimate of insulin resistance by HOMA score was calculated with the formula: fasting serum insulin (µIU/mL) x fasting plasma glucose (µM/L) / 22.5. There were no significant differences in age, body mass index, waist circumference, HOMA scores. There was a statistically significant difference in endothelium-dependent (FMD) and endothelium-independent vascular responses (NTG) between the patients with subclinical hypothyroidism and the normal healthy controls. The groups were well matched for baseline brachial artery diameter. The TSH and LDL, IL-6, TNF-alpha and hs-CRP levels in the patient group were significantly higher than those in control group. A positive correlation was found only between endothelium-dependent vasodilation and TNF-alpha, hs-CRP and IL-6, TSH, total cholesterol, LDL and triglycerides. Endothelium-independent vascular response was not correlated with any of the metabolic or hormonal parameters. Neither of the groups were insulin resistant and there was not any difference either in fasting insulin or in glucose levels. We found endothelial dysfunction in subclinical hypothyroidism group. Endothelium-dependent (FMD) and endothelium-independent vascular responses (NTG) were lower in patient group. Our findings suggest that there is endothelial dysfunction and low grade chronic inflammation in SH due to autoimmune thyroiditis. There are several contributing factors which can cause endothelial dysfunction in SH such as changes in lipid profile, hyperhomocysteinemia. According to our results low grade chronic inflammation may be one of these factors.


Amendment performance of an apodized tilted fiber Bragg grating for a quasi-distributed-based sensor.
In this work, the characteristics of reflectivity spectra produced inside a reflective-tilted fiber Bragg grating (R-TFBG) are investigated, seeking a remarkable performance that could be able to upgrade the sensitivity range for temperature-strain sensors of quasi-distribution type. We introduce an optimized performance through a comparative investigation among different evaluation parameters, such as core radius, tilt angle, and the elite selection of apodization profiles, in addition to the traditional parameters, such as grating length, L, and index modulation amplitude, Δn. Regarding the tilt angle, its increase affects the full width at half-maximum (FWHM) affirmatively, while having a negative impact on the maximum reflectivity. By controlling L and Δn, a compromised solution is achieved to retrieve the maximum reflectivity to be around 1.0. Regarding the sidelobes, the Kaiser profile is the best candidate that minimized the main sidelobe level (MSL) and raised the sidelobe suppression ratio (SLSR) at any tilt angle, while tanh apodization is the best choice from the perspective of raising the ramp down sidelobes asymptotic decay. The contrasts in the optimization process are examined through investigating the R-TFBG quasi-distributed sensors to be applied to a temperature-strain sensing system. The objective is to evaluate an assessment for the performance of a sensor system that extends the range and efficiency of temperature-strain ranges. Based on our analysis, the sensitivity range is upgraded for a temperature change to reach 179°C and for strain to be 3000 μϵ at a tilt angle of 10° with a FWHM of 0.063 nm, attenuation of -154 dB for an MSL of 75.5%, and an SLSR of -60 dB/nm.


The effects of different degrees of head-of-bed elevation on the respiratory pattern and drainage following thyroidectomy: a randomized controlled trial.
The patient's position is important for ensuring patient comfort and preventing complications after thyroidectomy. This study was carried out to determine the effects of different degrees of head-of-bed elevation (HOBE) on the respiratory pattern and drainage following thyroidectomy and to provide suggestions for evidence-based clinical practice. The sample of this prospective, parallel arm, randomized controlled trial included 114 patients undergoing thyroidectomy in a university hospital in Turkey. The patients were randomly assigned (1:1:1) to supine 0° (baseline), 30° and 45° HOBE groups. Respiratory pattern including respiratory rate (RR), peripheral oxygen saturation (SpO2) and dyspnea, and drainage including amount of drainage and hematoma formation were evaluated at the 1rd, 2rd, 3rd and 4th hours following thyroidectomy. The majority of the patients (83.3%) were female and 84.2% had undergone total thyroidectomy. The mean RR (18.47, 95% CI=17.85-19.09) of the patients in the supine 30° HOBE group at the 1rd hour was significantly higher than that of the patients in the supine 0° group (17.32, 95% CI=16.88-17.76; p<0.05). There was no significant difference between the SpO2 values of the patients in the groups (p>0.05). The amount of drainage was significantly higher in the supine 0° group at the 2nd hour than that of the patients in the supine 45° HOBE group (5.92±5.18; 3.34±5.56 respectively; p<0.05). None of the patients in the groups had hematoma formation. While no patient in the supine 30° HOBE group had dyspnea, dyspnea occurred in 9 patients in the supine 0° group and in 3 patients in the supine 45° HOBE group. This study showed that different HOBE positions resulted in clinically insignificant changes on the RR and amount of drainage during the first 4 hours following thyroidectomy but did not affect SpO2 value.


Survival outcomes of First Nations patients with oral cavity squamous cell carcinoma (Poliquin 2014).
Oral cavity squamous cell carcinoma (OCSCC) is the most common head and neck cancer, affecting approximately 2000 Canadians yearly. Analysis of Canadian Cancer Registry data has shown that the incidence of oral cavity cancer is decreasing and survival outcomes are improving. There are significant health disparities in First Nations (FN) people in Canada. The incidence of cancer in FN groups is significantly lower when compared to the general population, but the cancer-related morbidity and mortality is significantly higher. There is no Canadian literature currently for OCSCC, or any other head and neck cancer, that compares survival outcomes of FN to the overall population. Therefore, the objective of this study is to determine whether there is a difference in epidemiology and survival outcomes between FN and non-FN patients with OCSCC. This is a retrospective study of a population-based, prospectively-collected database from Alberta Cancer Registry (ACR). Patients with OCSCC, diagnosed and treated in Alberta between 1998 and 2009 were included. ACR data collected included patient gender, age at diagnosis, tobacco and alcohol use, FN status, TNM staging, performance status, date of death, cause of death, and follow-up. FN status was identified through the Alberta Health and Wellness registry and through postal code correlation for those who live on reserves. A total of 583 patients with OCSCC were included in this study. Of these, 19 were identified as being FN, leaving 564 non-FN patients. When comparing the FN and non-FN groups, there is no significant difference in baseline demographics. Estimated yearly incidences for OCSCC in the Alberta population (all ages) and FN patients are 1.74/100,000 and 1.32/100,000 respectively (p = 0.23). Significant differences are seen in overall survival (OS) (5-year OS 58.1% for non-FN and 33.7% for FN) and for disease-specific survival (DSS) (5-year DSS 67.8% for non-FN and 44.5% for FN). Multivariate analysis confirmed FN patients have a significant increase risk of death in OS and DSS, with hazard ratios of 4.20 (p = 0.01) and 4.57 (p = 0.02), respectively. The overall survival and disease specific survival are significantly lower in FN patients compared to non-FN patients with OCSCC.


Disparities between Aboriginal and non-Aboriginal perinatal mortality rates in Western Australia from 1980 to 2015.
Perinatal mortality rates are typically higher in Aboriginal than non-Aboriginal populations of Australia. This study aimed to examine the pattern of stillbirth and neonatal mortality rate disparities over time in Western Australia, including an evaluation of these disparities across gestational age groupings. All singleton births (≥20 weeks gestation) in Western Australia between 1980 and 2015 were included. Linked data were obtained from core population health datasets of Western Australia. Stillbirth and neonatal mortality rates and percentage changes in the rates over time were calculated by Aboriginal status and gestational age categories. From 1980 to 2015, data were available for 930 926 births (925 715 livebirths, 5211 stillbirths and 2476 neonatal deaths). Over the study period, there was a substantial reduction in both the Aboriginal (19.6%) and non-Aboriginal (32.3%) stillbirth rates. These reductions were evident in most gestational age categories among non-Aboriginal births and in Aboriginal term births. Concomitantly, neonatal mortality rates decreased in all gestational age windows for both populations, ranging from 32.1% to 77.5%. The overall stillbirth and neonatal mortality rate differences between Aboriginal and non-Aboriginal birth decreased by 0.6 per 1000 births and 3.9 per 1000 livebirths, respectively, although the rate ratios (RR 2.51, 95% CI 2.14, 2.94) and (RR 2.94, 95% CI 2.24, 3.85), respectively reflect a persistent excess of Aboriginal perinatal mortality across the study period. Despite steady improvements in perinatal mortality rates in Western Australia over 3½ decades, the gap between Aboriginal and non-Aboriginal rates remains unchanged in relative terms. There is a continuing, pressing need to address modifiable risk factors for preventable early mortality in Aboriginal populations.


Life history traits of Sirex noctilio F. (Hymenoptera: Siricidae) can explain outbreaks independently of environmental factors.
The woodwasp Sirex noctilio is a major pest of pine plantations worldwide. Economically significant damage is however limited to outbreak populations. To understand what determines outbreaks dynamics in this species, we developed an individual based model for a wasp population developing within a pine plantation. We show that outbreaks may be the result of the insect's life history. Specifically we show that limited dispersal may not only increase population persistence but also create the conditions for eruptive dynamics. When the probability of long distance dispersal is greater than zero, but relatively small (P(LDD) = 0.1) large outbreaks are the norm, with all of the suitable trees dead at the end of the simulation. For P(LDD) = 0 (only local dispersal allowed) outbreaks are smaller in size, and in some cases not well defined and spread over longer periods. For P(LDD) = 1 (only long distance dispersal allowed), the frequency of local population extinction (without outbreaks) increases significantly. Aggregated attacks may induce physiological changes in the trees which could allow other wasps to detect them. These changes may in turn trigger an outbreak. In contrast, healthy, vigorous trees are not suitable for wasp oviposition. In our model the density of suitable trees (healthy trees but yet suitable for oviposition) are a key factor determining population persistence before outbreaks. From an applied perspective, our results emphasize the importance of adequate plantation management in preventing woodwasp infestation.