Saturation of Fishbone Instability by Self-Generated Zonal Flows in Tokamak Plasmas.

Gyrokinetic simulations of the fishbone instability in DIII-D tokamak plasmas find that self-generated zonal flows can dominate the nonlinear saturation by preventing coherent structures from persisting or drifting in the energetic particle phase space when the mode frequency down-chirps. Results from the simulation with zonal flows agree quantitatively, for the first time, with experimental measurements of the fishbone saturation amplitude and energetic particle transport. Moreover, the fishbone-induced zonal flows are likely responsible for the formation of an internal transport barrier that was observed after fishbone bursts in this DIII-D experiment. Finally, gyrokinetic simulations of a related ITER baseline scenario show that the fishbone induces insignificant energetic particle redistribution and may enable high performance scenarios in ITER burning plasma experiments.

[Translated article] Glucagon-Like Peptide-1 Agonists for Treating Obesity in Patients With Immune-Mediated Skin Diseases / Agonistas del receptor de GLP-1 para el tratamiento de la obesidad en pacientes con dermatosis inmunomediadas

Psoriasis and hidradenitis suppurativa are often associated with obesity. Because chronic low-grade inflammation underlies these 2 diseases, they can progress to more severe forms in patients with obesity if weight-reduction measures are not taken. This review covers pharmacologic alternatives for treating obesity, with emphasis on the benefits associated with the novel use of glucagon-like peptide-1 (GLP-1) agonists that act on satiety receptors. These drugs have led to greater weight loss in clinical trials and real-world settings than orlistat, which until recently was the only drug approved for treating obesity in the European Union. Although experience with GLP-1 agonists in patients with obesity and inflammatory skin diseases is currently scarce, the promising results reported suggest they may offer a useful tool for managing obesity (AU)

La psoriasis (PsO) y la hidradenitis supurativa (HS) se asocian frecuentemente con la obesidad. La inflamación crónica de bajo grado subyace a estas condiciones, por lo que si no se adoptan medidas para reducir el peso del paciente con obesidad y PsO o HS, estas podrían evolucionar hacia formas más graves. Este trabajo revisa las opciones farmacológicas para tratar la obesidad, profundizando en los beneficios asociados al uso novedoso de agonistas del receptor de GLP-1 (arGLP-1), que actúan sobre los centros de la saciedad. Los resultados de ensayos y vida real demuestran que esta medicación consigue mayores pérdidas de peso que orlistat, hasta recientemente el único fármaco específico para la obesidad comercializado en la Unión Europea. Aunque la experiencia con arGLP-1 en pacientes con obesidad y dermatosis inflamatorias es escasa, los resultados son alentadores, por lo que podrían constituir una herramienta útil para el manejo de su obesidad (AU)

Agonistas del receptor de GLP-1 para el tratamiento de la obesidad en pacientes con dermatosis inmunomediadas / Glucagon-Like Peptide-1 Agonists for Treating Obesity in Patients With Immune-Mediated Skin Diseases

La psoriasis (PsO) y la hidradenitis supurativa (HS) se asocian frecuentemente con la obesidad. La inflamación crónica de bajo grado subyace a estas condiciones, por lo que si no se adoptan medidas para reducir el peso del paciente con obesidad y PsO o HS, estas podrían evolucionar hacia formas más graves. Este trabajo revisa las opciones farmacológicas para tratar la obesidad, profundizando en los beneficios asociados al uso novedoso de agonistas del receptor de GLP-1 (arGLP-1), que actúan sobre los centros de la saciedad. Los resultados de ensayos y vida real demuestran que esta medicación consigue mayores pérdidas de peso que orlistat, hasta recientemente el único fármaco específico para la obesidad comercializado en la Unión Europea. Aunque la experiencia con arGLP-1 en pacientes con obesidad y dermatosis inflamatorias es escasa, los resultados son alentadores, por lo que podrían constituir una herramienta útil para el manejo de su obesidad (AU)

Psoriasis and hidradenitis suppurativa are often associated with obesity. Because chronic low-grade inflammation underlies these 2 diseases, they can progress to more severe forms in patients with obesity if weight-reduction measures are not taken. This review covers pharmacologic alternatives for treating obesity, with emphasis on the benefits associated with the novel use of glucagon-like peptide-1 (GLP-1) agonists that act on satiety receptors. These drugs have led to greater weight loss in clinical trials and real-world settings than orlistat, which until recently was the only drug approved for treating obesity in the European Union. Although experience with GLP-1 agonists in patients with obesity and inflammatory skin diseases is currently scarce, the promising results reported suggest they may offer a useful tool for managing obesity (AU)

Glucagon-Like Peptide-1 Agonists for Treating Obesity in Patients With Immune-Mediated Skin Diseases. / Agonistas del receptor de GLP-1 para el tratamiento de la obesidad en pacientes con dermatosis inmunomediadas.

Psoriasis and hidradenitis suppurativa are often associated with obesity. Because chronic low-grade inflammation underlies these 2 diseases, they can progress to more severe forms in patients with obesity if weight-reduction measures are not taken. This review covers pharmacologic alternatives for treating obesity, with emphasis on the benefits associated with the novel use of glucagon-like peptide-1 (GLP-1) agonists that act on satiety receptors. These drugs have led to greater weight loss in clinical trials and real-world settings than orlistat, which until recently was the only drug approved for treating obesity in the European Union. Although experience with GLP-1 agonists in patients with obesity and inflammatory skin diseases is currently scarce, the promising results reported suggest they may offer a useful tool for managing obesity.

[Translated article] Glucagon-Like Peptide-1 Agonists for Treating Obesity in Patients With Immune-Mediated Skin Diseases.

Psoriasis and hidradenitis suppurativa are often associated with obesity. Because chronic low-grade inflammation underlies these 2 diseases, they can progress to more severe forms in patients with obesity if weight-reduction measures are not taken. This review covers pharmacologic alternatives for treating obesity, with emphasis on the benefits associated with the novel use of glucagon-like peptide-1 (GLP-1) agonists that act on satiety receptors. These drugs have led to greater weight loss in clinical trials and real-world settings than orlistat, which until recently was the only drug approved for treating obesity in the European Union. Although experience with GLP-1 agonists in patients with obesity and inflammatory skin diseases is currently scarce, the promising results reported suggest they may offer a useful tool for managing obesity.

Drought conditions, aridity and forest structure control the responses of Iberian holm oak woodlands to extreme droughts: A large-scale remote-sensing exploration in eastern Spain.

Understanding how Mediterranean forests respond to the increasing frequency of extreme droughts and forest densification is crucial for effective land management in the present context of climate change and land abandonment. We study the responses of Iberian holm oak (Quercus ilex L.) woodlands to recent extreme droughts during 2000-2019 along broad gradients of climate aridity and forest structure. To this purpose, we apply large-scale remote-sensing using MODIS EVI as a primary production proxy in 5274 Q. ilex sites distributed within a 100,000 km2 region in eastern Spain. These woodlands were extensively affected by two extreme drought events in 2005 and 2012. Resistance, assessed as the capacity of the ecosystems to maintain primary production during drought, was significantly lower for semi-arid than for sub-humid and dry-transition conditions. Holm oak woodlands located in semi-arid areas of the region showed also poorer resilience to drought, characterized by low capacity to fully recover to their pre-drought production levels. Further, drought intensity and both pre- and post-drought hydric conditions controlled the variations of resistance, recovery and resilience between the two analyzed extreme drought events. Drought effects were particularly negative for dense Q. ilex stands under semi-arid climate conditions, where strong competition for scarce water resources reduced drought resistance. The observed drought vulnerability of semi-arid holm oak woodlands may affect the long-term stability of these dry forests. Adaptive management strategies, such as selective forest thinning, may be useful for improving drought responses in these more vulnerable semi-arid woodlands. Conversely, natural rewilding may more appropriately guide management actions for more humid areas, where densely developed Q. ilex woodlands show in general a high ability to maintain ecosystem primary production during drought.

Diabetes might not be a risk factor for worse prognosis among hospitalized patients due to COVID-19 in a Mediterranean area / La presencia de diabetes entre los pacientes ingresados por COVID-19 podría no ser un factor de peor pronóstico

Aim: type-2 diabetes (T2DM) seems to worsen the prognosis of patients admitted for COVID-19, although most studies included Asiatic patients. We aimed to assess whether this condition applies for Mediterranean patients. Methods: a total of 90 patients admitted for COVID-19 with T2DM were retrospectively compared with 50 patients without T2DM. Results: subjects with T2DM were older than their counterparts (73.3 ± 12.4 vs 53 ± 15.7 years; p < 0.0001). Either absolute lymphocyte count (1.1 ± 0.6 vs 1.3 ± 0.7 x 109/L; p = 0.005) or hemoglobin (11.9 ± 1.6 vs 13.1 ± 2.1 g/dL; p < 0.0001) were lower among subjects with T2DM. CRP and procalcitonin were higher among subjects with T2DM (91.9 ± 71.2 vs 70.1 ± 63.3 mg/L; p = 0.002 and 0.8 ± 0.3 vs 0.4 ± 0.1 ng/mL; p < 0.0001, respectively). Albumin was lower among patients with T2DM (3.4 ± 0.5 vs 3.8 ± 0.5 g/L: p < 0.001). Length of stay was longer among subjects with T2DM (11.7 ± 7.7 vs 9.7 ± 8.6 days; p = 0.01). However, both groups were comparable regarding both the proportion of subjects who were admitted to the ICU (16.5 % vs 8 %; p = 0.1) and mortality (11 % vs 4 %; p = 0.2). Conclusions: in a Mediterranean sample, despite of age, comorbidities, nutritional status, and inflammatory markers, subjects with T2DM with a proper glycemic control admitted for COVID-19 had similar prognostic outcomes than patients without this metabolic condition (AU)

Objetivo: la diabetes de tipo 2 (DM2) parece empeorar el pronóstico de los pacientes ingresados por COVID-19, aunque la mayoría de los estudios incluyeron pacientes asiáticos. Nuestro objetivo fue evaluar si esto se aplica a los pacientes de una población Mediterránea. Métodos: un total de 90 pacientes ingresados por COVID-19 con DM2 se compararon retrospectivamente con 50 pacientes sin DM2. Resultados: los sujetos con DM2 eran mayores que sus contrapartes (73,3 ± 12,4 frente a 53 ± 15,7 años; p < 0,0001). El recuento absoluto de linfocitos (1,1 ± 0,6 vs. 1,3 ± 0,7 x 109/L; p = 0,005) o la hemoglobina (11,9 ± 1,6 vs. 13,1 ± 2,1 g/dL; p < 0,0001) fueron menores entre los sujetos con DM2. La PCR y la procalcitonina fueron mayores entre los sujetos con DM2 (91,9 ± 71,2 frente a 70,1 ± 63,3 mg/L; p = 0,002 y 0,8 ± 0,3 frente a 0,4 ± 0,1 ng/ml; p < 0,0001, respectivamente). La albúmina fue menor entre los pacientes con DM2 (3,4 ± 0,5 vs. 3,8 ± 0,5 g/L: p < 0,001). La estancia hospitalaria fue mayor entre los sujetos con DM2 (11,7 ± 7,7 frente a 9,7 ± 8,6 días; p = 0,01). Sin embargo, ambos grupos fueron comparables en cuanto a la proporción de sujetos con ingreso en la UCI (16,5 % vs. 8 %; p = 0,1) y la mortalidad (11 % vs. 4 %; p = 0,2). Conclusiones: en una muestra mediterránea, a pesar de la edad, las comorbilidades, el estado nutricional y los marcadores inflamatorios, los sujetos con DM2 con un adecuado control glucémico ingresados por COVID-19 tuvieron resultados pronósticos similares a los de los pacientes sin esta condición metabólica (AU)

Regulation of Alfvén Eigenmodes by Microturbulence in Fusion Plasmas.

Global gyrokinetic simulations of mesoscale reversed shear Alfven eigenmodes (RSAE) excited by energetic particles (EP) in fusion plasmas find that RSAE amplitude and EP transport are much higher than experimental levels at nonlinear saturation, but quickly diminish to very low levels after the saturation if background microturbulence is artificially suppressed. In contrast, in simulations coupling micro-meso scales, the RSAE amplitude and EP transport decrease drastically at the initial saturation but later increases to the experimental levels in the quasisteady state with bursty dynamics due to regulation by thermal ion temperature gradient (ITG) microturbulence. The quasisteady state EP transport is larger for a stronger microturbulence. The RSAE amplitude in the quasisteady state ITG-RSAE turbulence from gyrokinetic simulations, for the first time, agrees very well with experimental measurements.

Thyroid as a target of adjuvant autoimmunity/inflammatory syndrome due to mRNA-based SARS-CoV2 vaccination: from Graves' disease to silent thyroiditis.

BACKGROUND: As COVID-19 became a pandemic, the urgent need to find an effective treatment vaccine has been a major objective. Vaccines contain adjuvants which are not exempt from adverse effects and can trigger the autoimmune/inflammatory syndrome induced by adjuvants (ASIA). There is very little information about autoimmune endocrine disease and the ASIA after the use of mRNA-based SARS-CoV2 vaccination. CASE SERIES: We report three cases and also review the literature showing that the thyroid gland can be involved in the ASIA induced by the mRNA-based SARS-CoV2 vaccination. We present the first case to date of silent thyroiditis described in the context of SARS-CoV2 vaccination with Pfizer/BioNTech. Also, we discuss the first subacute thyroiditis in the context of SARS-CoV2 vaccination with the Moderna's vaccine. Finally, we provide another case to be added to existing evidence on Graves' disease occurring post-vaccination with the Pfizer/BioNTech vaccine. DISCUSSION: Adjuvants play an important role in vaccines. Their ability to increase the immunogenicity of the active ingredient is necessary to achieve the desired immune response. Both the Moderna and the Pfizer/BioNTech vaccines use mRNA coding for the SARS-CoV2 S protein enhanced by adjuvants. In addition, the cross-reactivity between SARS-CoV2 and thyroid antigens has been reported. This would explain, at least, some of the autoimmune/inflammatory reactions produced during and after SARS-CoV2 infection and vaccination. CONCLUSION: The autoimmune/inflammatory syndrome induced by adjuvants involving the thyroid could be an adverse effect of SARS-CoV2 vaccination and could be underdiagnosed.

Fermentative volatile fatty acid production and recovery from grass using a novel combination of solids separation, pervaporation, and electrodialysis technologies.

A novel combination of solids screening, centrifugation, microfiltration, pervaporation, and electrodialysis were used for the targeted and exclusive recovery of volatile fatty acids (VFAs) from an 80L bioreactor. The bioreactor was continually-fed with grass waste, containing 40gL-1 total solids, over three, seven-day, hydraulic retention times. A VFA solution with a concentration up to 4,500 mgL-1 was recovered. VFA yields were also increased from 707 to 875 mg of VFA per gram of volatile solids by alleviating end-product inhibition. Both these accomplishments are significant step-changes in adding value to waste, and increased substrate utilisation rates will be attractive from a waste remediation perspective.

Clinically significant intra-day variability of serum progesterone levels during the final day of oocyte maturation: a prospective study with repeated measurements.

STUDY QUESTION: Is there significant variability in progesterone levels during the final day of oocyte maturation in women undergoing ovarian stimulation? SUMMARY ANSWER: Progesterone levels drop from the basal level up to 44% during the final day of oocyte maturation in women undergoing ovarian stimulation. WHAT IS KNOWN ALREADY: It has been suggested that elevated progesterone levels on the final day of ovarian stimulation may be related to poorer outcomes in in vitro fertilization fresh cycles due to a negative impact on the endometrium. However, despite conflicting results regarding the actual effect of progesterone on pregnancy rates and the lack of a well-established cut off, currently many IVF patients have their embryo transfer deferred when progesterone values surpass a threshold of 1.5 ng/ml on the day of ovulation triggering. STUDY DESIGN, SIZE, DURATION: This was a prospective cohort study conducted in 22 oocyte donors of a university-affiliated fertility centre between November 2017 and January 2018. We calculated the sample size to detect a difference of 15% between the first and last progesterone measurements with a 5% false-positive rate in a two-sided test with 80% statistical power and a 95% confidence interval (CI). PARTICIPANTS/MATERIALS, SETTING, METHODS: Progesterone circulating levels were evaluated at four different times during the final day of oocyte maturation (08:00, 12:00, 16:00 and 20:00) before ovulation triggering in healthy oocyte donors. A flexible antagonist protocol was used, and ovarian stimulation was achieved with recombinant follicle-stimulating hormone (FSH) in all cases. The pairwise percentage differences in progesterone levels for each patient were calculated. Univariate linear regression analysis was adopted in order to evaluate variables associated with progesterone levels on the first measurement. The intra-day variability of progesterone was analysed using mixed models. MAIN RESULTS AND THE ROLE OF CHANCE: Mean serum progesterone values at 08:00, 12:00, 16:00 and 20:00 were 1.75 ng/ml, 1.40 ng/ml, 1.06 ng/ml and 0.97 ng/ml. The progesterone difference between 08:00 and 20:00 was 0.77 (95% CI, 0.56-0.99), which is equivalent to a 44% decline in the mean progesterone values between the first (08:00) and the last determination (20:00; P < 0.001). Among those patients with basal (08:00) progesterone levels >1.5 ng/ml (n = 10), 70% (n = 7) showed levels reduced to <1.5 ng/ml on the last determination of the day (20:00). A mixed model analysis revealed that the progesterone reduction during the day was significantly associated with time and total recombinant FSH dose administered. LIMITATIONS, REASONS FOR CAUTION: Only young healthy oocyte donors stimulated with an antagonist protocol using recombinant FSH were included. Extrapolation to the general IVF population, with different stimulation protocols and gonadotropins, needs to be confirmed. WIDER IMPLICATIONS OF THE FINDINGS: This study suggests that a single progesterone determination on the final day of oocyte maturation is not reliable enough to make clinical decisions due to the enormous variation in progesterone during the day. Further studies are needed to better define the impact of the follicular progesterone rise on the endometrium of IVF cycles. STUDY FUNDING/COMPETING INTEREST(S): Funding was granted from Fundació Santiago Dexeus Font. N.P.P. received unrestricted grants and/or lectures fees from Roche Diagnostics, MSD, Merck, Ferring Pharmaceuticals, IBSA, Theramex and BESINS International, not associated with the current study. The remaining authors have no competing interests. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT03366025.

Differences in the cluster of depressive symptoms between subjects with type 2 diabetes and individuals with a major depressive disorder and without diabetes.

BACKGROUND: Depressive disorder encompasses a wide spectrum of somatic and psychological symptoms. It is not known whether there are differences regarding the cluster of depressive symptomatology between subjects with depression with and without T2DM. PURPOSE: To explore whether the cluster of depression that prevails among depressive subjects with T2DM differs from individuals with depression, but without T2DM. METHODS: 87 T2DM patients with a pathological Beck Depression Inventory test (BDI) were compared with 50 age- and gender-matched individuals with a major depressive disorder. All 21 items expressed in the BDI were compared between the two groups. RESULTS: The score obtained after administering the BDI was comparable between patients with T2DM and significant depressive symptoms and the control group (18.8 ± 2.7 vs 18.9 ± 3.4; p = 0.9). Subjects with T2DM had higher scores compared with the control group in the following items: sadness (1.4 ± 0.9 vs 0.9 ± 0.9; p = 0.011), difficulty in concentration (1.3 ± 0.8 vs 0.8 ± 0.8; p = 0.01), indecisiveness (1.1 ± 0.8 vs 0.5 ± 0.9; p = 0.012), worries about their health (1.3 ± 0.9 vs 0.6 ± 0.9; p < 0.0001), fatigue (1.2 ± 0.6 vs 0.8 ± 0.7; p = 0.003) and loss of sexual appetite (2.7 ± 0.6 vs 1.2 ± 1.3; p = 0.0001). Suicidal ideation was significantly lower among subjects with T2DM compared with the control group (0.1 ± 0.3 vs 0.6 ± 0.8; p = 0.0001). CONCLUSIONS: Subjects with T2DM and a positive screening for depression presented a different cluster of depression compared with depressed subjects without T2DM, with a predominance of somatic-biological depressive symptoms rather than psychological-cognitive cluster and negative emotions, such as suicidal ideation.

[The REDSIAM network]. / Le réseau REDSIAM (Réseau données Sniiram) ­ Spécial REDSIAM.

The French national health database (SNIIRAM) proved to be very useful for epidemiology, health economics, evaluation, surveillance or public health. However, it is a complex database requiring important resources and expertise for being used. The REDSIAM network has been set up for promoting the collaboration of teams working on the Sniiram. The main aim of REDSIAM is to develop and validate methods for analyzing the Sniiram database for research, surveillance, evaluation and public health purposes by sharing the knowledge and experience of specialized teams in the fields of diseases identification from the Sniiram data. The work conducted within the network is devoted to the development and the validation of algorithms using Sniiram data for identifying specific diseases. The REDSIAM governance includes the Steering Committee composed of the main organizations in charge of producing and using the Sniiram data, the Bureau and the Technical Committee. The network is organized in thematic working groups focused on specific pathological domains, and a charter defines the rules for participation in the network, the functioning of the thematic working groups, the rules for publishing and making available algorithms. The articles in this special issue of the journal present the first results of some of the thematic working groups.

Prevalence and Clinical Correlators of Undiagnosed Significant Depressive Symptoms Among Individuals with Type 2 Diabetes In A Mediterranean Population.

Objective: To determine the frequency and clinical parameters, of clinically significant depressive symptoms among a type 2 diabetes (T2DM) sample from a Mediterranean area without an established diagnosis of depressive disorder (DD). Methods: 320 subjects with T2DM were recruited randomly from Primary-Care settings and the Endocrine Department from a tertiary center in Mallorca (Spain). 91 healthy individuals matched by age, gender and BMI were used as controls. All participating patients graded by the presence of DD by using the "Beck Depression Inventory" (BDI), considering pathological a cut-off score equal or greater than 16. Results: 27.2% T2DM subjects had significant symptoms of DD compared with 12.1% in the control group (p<0.01). BDI score was higher among T2DM when compared with controls (12±9.6 vs. 7.4±5, p<0.0001). The proportion of females (68% vs. 37%, p<0.0001), subjects without an active job (68% vs. 45%, p=0.01) and singles (38% vs. 18%, p=0.007) was greater among T2DM with a BDI≥16. Subjects with criteria for DD had a higher BMI (31.99±5.96 vs. 30.53±5.62, p=0.03). Fasting plasma glucose was higher among T2DM with a BDI≥16 (162±70 vs. 147±45 mg/dl, p=0.02) as well as HbA1c levels (7.9±1.8% vs. 7.4±1.4%, p=0.01), triglycerides (203±183 vs. 161±103 mg/dl; p=0.03) and LDL-cholesterol (112±31 vs. 104±35 mg/dl; p=0.03). Gender, marital status, BMI and triglycerides were independently related to the presence of DD after a logistic regression model. Conclusions: Relevant depressive symptoms are more prevalent among Mediterranean T2DM subjects than in general population. Main clinical correlators of significant depressive symptoms are gender, marital status and BMI.

Phosphoric acid concentration affects dentinal MMPs activity.

OBJECTIVES: To evaluate whether the concentration of phosphoric acid (PA) has an effect on the proteolytic activity of sound human demineralized dentin. It is hypothesized that the activity of matrix-bound and extracted enzymes depends on the PA concentration used to demineralize dentin. METHODS: One-gram aliquots of mid-coronal human dentin powder were demineralized with 1wt%, 10wt% and 37wt% PA. Concentrations of released calcium were measured for each set of demineralization. Extracted MMP-2 was immunologically identified by western blot and its activity was determined by conventional gelatin zymography. Analysis of released hydroxyproline (HYP) and in situ zymography were performed to evaluate the activity of insoluble, bound-matrix enzymes. RESULTS: The amount of released calcium from dentin powder treated with 37wt% PA was significantly higher (p≤0.05) than that obtained by dentin demineralization with 10wt% and 1wt% PA. Expression and activity of endogenous enzymes, extracted from or bound to dentin matrix, were detected for all samples regardless of the PA concentration. However, the expression and activity of extracted MMP-2 were significantly higher when dentin was treated with 10wt% PA (p<0.05), followed by 1wt% and 37wt% PA. Similarly, the highest concentration of released HYP (i.e. meaning higher percentage of collagen degradation) and the highest activity in in situ zymography were observed when dentin samples were treated with 10wt% PA (p<0.05). CONCLUSIONS: It was confirmed that PA does not denature endogenous enzymes of dentin matrices, but it may somehow modulate the expression and activity of these enzymes in a concentration-dependent manner. CLINICAL SIGNIFICANCE: Endogenous proteases have been identified and suggested to be responsible for the digestion of dentin matrix when activated by the acidic components of dental adhesives. Proteolytic activity of dentinal MMPs showed to be dependent on phosphoric acid concentration. The clinically-used concentration (37%) does not inhibit MMPs activity, but slows it.

Lithium Induces Glycogen Accumulation in Salivary Glands of the Rat.

Lithium is administered for the treatment of mood and bipolar disorder. The aim of this study was to verify whether treatment with different concentrations of lithium may affect the glycogen metabolism in the salivary glands of the rats when compared with the liver. Mobilization of glycogen in salivary glands is important for the process of secretion. Two sets of experiments were carried out, that is, in the first, the rats received drinking water supplemented with LiCl (38,25 and 12 mM of LiCl for 15 days) and the second experiment was carried out by intraperitoneal injection of LiCl solution (12 mg/kg and 45 mg LiCl/kg body weight) for 3 days. The active form of glycogen phosphorylase was not affected by treatment with LiCl considering the two experiments. The active form of glycogen synthase presented higher activity in the submandibular glands of rats treated with 25 and 38 mM LiCl and in the liver, with 25 mM LiCl. Glycogen level was higher than that of control in the submandibular glands of rats receiving 38 and 12 mM LiCl, in the parotid of rats receiving 25 and 38 mM, and in the liver of rats receiving 12 mM LiCl. The absolute value of glycogen for the submandibular treated with 25 mM LiCl, and the liver treated with 38 mM LiCl, was higher than the control value, although not statistically significant for these tissues. No statistically significant difference was found in the submandibular and parotid salivary glands for protein concentration when comparing experimental and control groups. We concluded that LiCl administered to rats influences the metabolism of glycogen in salivary glands.

Health economic analysis of ticagrelor in patients with acute coronary syndromes intended for non-invasive therapy.

OBJECTIVE: To investigate the cost effectiveness of ticagrelor versus clopidogrel in patients with acute coronary syndromes (ACS) in the Platelet Inhibition and Patient Outcomes (PLATO) study who were scheduled for non-invasive management. METHODS: A previously developed cost effectiveness model was used to estimate long-term costs and outcomes for patients scheduled for non-invasive management. Healthcare costs, event rates and health-related quality of life under treatment with either ticagrelor or clopidogrel over 12 months were estimated from the PLATO study. Long-term costs and health outcomes were estimated based on data from PLATO and published literature sources. To investigate the importance of different healthcare cost structures and life expectancy for the results, the analysis was carried out from the perspectives of the Swedish, UK, German and Brazilian public healthcare systems. RESULTS: Ticagrelor was associated with lifetime quality-adjusted life-year (QALY) gains of 0.17 in Sweden, 0.16 in the UK, 0.17 in Germany and 0.13 in Brazil compared with generic clopidogrel, with increased healthcare costs of €467, €551, €739 and €574, respectively. The cost per QALY gained with ticagrelor was €2747, €3395, €4419 and €4471 from a Swedish, UK, German and Brazilian public healthcare system perspective, respectively. Probabilistic sensitivity analyses indicated that the cost per QALY gained with ticagrelor was below conventional threshold values of cost effectiveness with a high probability. CONCLUSIONS: Treatment of patients with ACS scheduled for 12 months' non-invasive management with ticagrelor is associated with a cost per QALY gained below conventional threshold values of cost effectiveness compared with generic clopidogrel. TRIAL REGISTRATION NUMBER: NCT000391872.

Sensitivity and specificity of serological tests, histopathology and immunohistochemistry for detection of Toxoplasma gondii infection in domestic chickens.

Since free-range chickens are important for the epidemiology of toxoplasmosis, this study evaluated the sensitivity and specificity of different laboratory techniques for the diagnosis of Toxoplasma gondii in these animals. Serum samples from 135 adult domestic chickens were tested for anti-T. gondii antibodies by the indirect fluorescent antibody test (IFAT), enzyme-linked immunosorbent assay (ELISA), modified agglutination test (MAT), and indirect hemagglutination test (IHAT). Tissue samples from all animals were analyzed by histopathology, immunohistochemistry and mouse bioassay (gold standard). Fifty-four chickens were positive for T. gondii in the bioassay. The sensitivity and specificity of the different tests were, respectively, 85% and 56% for ELISA; 80% and 52% for IFAT; 76% and 68% for MAT; 61% and 80% for IHAT; 7% and 98% for immunohistochemistry, and 6% and 98% for histopathology. The MAT was the most effective method for the diagnosis of T. gondii infection in chickens, followed by ELISA. Histopathology and immunohistochemistry are useful tools for the diagnosis of T. gondii infection in chickens due to their specificity.

[Admissions for pediatric asthma in France]. / Les hospitalisations pour asthme chez l'enfant en France, 2002-2010.

INTRODUCTION: Most hospital admissions for asthma exacerbation are avoidable with adequate disease management. The objective of this study was to describe admissions for asthma in children in France using data from the French nationwide hospital database. METHODS: We selected admissions having either a main diagnosis of asthma or a main diagnosis of acute respiratory failure (ARF) with asthma as an associated diagnosis, occurring in children (age<15years) between 2002 and 2010 in France (excluding French Guyana). RESULTS: In 2010, 35,004 asthma admissions and 1381 cases of asthma-related ARF were recorded (crude admission rate, 30.1/10,000 children); the mean length of stay was 2days. The in-hospital lethality rate ranged from 0.01% to 0.03% depending on the year. The annual age-standardized admission rate increased between 2002 and 2010 (+2.5% per year on average in metropolitan France). In 2010, 11.8% of children admitted for asthma or asthma-related ARF were readmitted for asthma or asthma-related ARF at least once within the same calendar year, and 1.3% were readmitted within the week following admission. The proportion of children aged less than 5 years who were readmitted within the same calendar year increased between 2002 and 2010. CONCLUSION: The increase in admission and readmission rates indicates non-optimal management of asthma in children in France.