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PURPOSE: To compare the effects of insulin sensitizers metformin (MET) and myo-inositol (MI) on adiponectin levels and metabolic characteristics in women with polycystic ovary syndrome (PCOS) with respect to their body mass index (BMI). METHODS: In this open label, parallel randomized clinical trial, 66 women with PCOS (33 normal-weight and 33 overweight/obese) were randomized to either MI (4 g/day) or MET (1500 mg/day) for a period of 6 months. Serum concentration of adiponectin, hormonal and metabolic laboratory outcomes and clinical assessment of BMI, body composition and Ferriman-Gallwey score (FG score) were evaluated before and after treatment. RESULTS: After the 6-month intervention, comparison between MET and MI in time to treatment analysis showed no significant differences between the two treatments for all analyzed parameters. Only borderline significantly lower AUC glucose was found in the MET group in comparison to the MI group (p = 0.071). The main effect of treatment was shown for glucose concentration at 120 min OGTT (p = 0.032) and testosterone (p = 0.002). The main effect of time was shown for body mass (p = 0.004), waist circumference (p < 0.001), BMI (p = 0.003), body fat mass (p = 0.001), adiponectin (p = 0.020), fasting glucose (p = 0.001), testosterone (p = 0.015), SHBG (p = 0.013), 17OH progesterone (p = 0.008), LH (p = 0.004) and estradiol (p = 0.014). CONCLUSION: Our study showed similar effects of MET and MI on BMI, body composition, hormonal profile, metabolism of glucose and insulin, and adiponectin level. The two insulin sensitizers, MET and MI, were useful in reducing BMI and improving body composition without significant differences between the two treatments in PCOS women. TRIAL REGISTRATION: ISRCTN13199265. Trial registration date: 14.04.2021. (ISRCTN Registry), retrospectively registered.
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Adiponectina/sangre , Hormonas Esteroides Gonadales/sangre , Inositol/administración & dosificación , Metformina/administración & dosificación , Obesidad , Síndrome del Ovario Poliquístico , Adulto , Glucemia/análisis , Composición Corporal , Índice de Masa Corporal , Femenino , Humanos , Hipoglucemiantes/administración & dosificación , Insulina/sangre , Resistencia a la Insulina , Obesidad/complicaciones , Obesidad/diagnóstico , Obesidad/metabolismo , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/diagnóstico , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/metabolismo , Resultado del Tratamiento , Complejo Vitamínico B/administración & dosificaciónRESUMEN
AIMS: This research aimed to isolate and characterize nonrhizobial endophytic bacteria from root nodules of Medicago sativa L. and Lotus corniculatus L. with plant growth-promoting characteristics and to test its activity in a pot experiment with acid soil. METHODS AND RESULTS: Out of 44 nonrhizobial isolates, the majority exhibited indole-3-acetic acid (IAA) production; 29 produced siderophores, few isolates performed phosphate solubilization and/or produced lytic enzymes, while 30% of isolates showed notable antifungal activity. The most promising strains were identified as members of Bacillus, Pseudomonas and Serratia genera, based on 16S rRNA. Bacillus megaterium DZK1BH exhibited the overall best attributes for plant growth promotion and positively influenced the growth of L. corniculatus and Dactylis glomerata. CONCLUSIONS: Root nodule endophytic B. megaterium DZK1BH could potentially be used as a biofertilizer for growing L. corniculatus L. and D. glomerata L. in acid soils, while Bacillus mojavensis L3 is a candidate for further antifungal potential investigation. SIGNIFICANCE OF IMPACT OF THE STUDY: The use of root nodule endophytic bacteria with PGP traits may find its future application in organic agriculture, as their utilization could decrease the use of chemical fertilizers and pesticides and simultaneously promote plant growth, especially in soils with low production quality.
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Lotus , Bacillus , Bacterias/genética , Dactylis , Endófitos/genética , Raíces de Plantas , ARN Ribosómico 16S/genéticaRESUMEN
CONTEXT: Cardiovascular risk is increased in women with polycystic ovary syndrome (PCOS). Do insulin sensitizing agents such as metformin (MET) and myoinositol (MI) ameliorate biomarkers of cardiovascular risk? OBJECTIVE: To compare the effects of MET and MI on blood pressure, lipid profile and high sensitive C-reactive protein (hs-CRP) in women with PCOS in respect to their body mass index (BMI). DESIGN: Open label, parallel randomized, single center study. SUBJECTS AND METHODS: Sixty six women with PCOS (33 normal-weight and 33 overweight/obese) were randomized to either MI (4 g/day) or MET (1500 mg/day) for a period of 6 months. Serum concentration of hormones, lipid profile, oxidized LDL (ox-LDL), hs-CRP, blood pressure measurement and clinical assessment of BMI, waist circumference (WC) and Ferriman Gallwey score (FG score) were performed before and after treatment. RESULTS: Thirty patients in each group completed the trial. Compared with MET, MI significantly decreased diastolic blood pressure (DBP) (p=0.036) and significantly increased serum hs-CRP (p=0.043). No differences between groups in total cholesterol (TC), HDL-cholesterol, LDL-cholesterol, ox-LDL and triglycerides were reported after 6 months. Treatment with MI reduced BMI (p=0.037), WC (p=0.005), DBP (p=0.021) and TC (p=0.008). During MET treatment a significant decrease in BMI (p=0.005), WC (p=0.004), FG score (p=0.001), testosterone (p=0.013) and free androgen index (FAI) (p=0.006) was observed. CONCLUSIONS: Our study showed an advantage of MI in reduction of DBP and TC thus predicting favorable metabolic and cardiovascular outcomes in PCOS women. MET more effectively decrease indices of hyperandrogenism.
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It is well known the use of ketamine and etomidate in clinical practice; however, the difference in the systemic effects of these two anesthetic agents is still debatable. Thus, in the present study we aimed to compare their effects on heart, and other organs through estimation of cardiodynamics, biochemical and hematological parameters. Male Wistar rats were divided in 2 groups containing of 2 subgroups (n = 7 in each subgroup, n = 28 in total): (1) bolus injection of anesthetic ketamine (40 mg/kg b.w., i.p. n = 14); (2) bolus injection of anesthetic etomidate (20 mg/kg b.w., i.p. n = 14). The experiments were done in vitro in one subgroup of each group: cardiodynamic variables (dp/dtmax, dp/dtmin, heart rate), coronary flow, oxidative stress in coronary effluent and cardiac tissue homogenate, and in vivo in another subgroup: biochemical and hematological parameters, and oxidative stress in haemolysate. Significantly increased left ventricular contractility (dp/dtmax) and relaxation (dp/dtmin) were noticed in etomidate group. Creatinine (CREA), HDL cholesterol and folate were significantly higher in etomidate group, whereas amylase (AMY) and eosinophils in ketamine group. Our results suggested that ketamine has more antioxidant potential compared to etomidate, and etomidate has more favorable effects regarding cardiac performance.
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Etomidato/farmacología , Corazón/efectos de los fármacos , Ketamina/farmacología , Estrés Oxidativo/efectos de los fármacos , Anestésicos Disociativos/farmacología , Anestésicos Intravenosos/farmacología , Animales , Fenómenos Fisiológicos Cardiovasculares , Masculino , Ratas , Ratas WistarRESUMEN
AIMS: The characterization of bacterial communities diversity on four local plum cultivars in two phenological stages using culture-dependent and culture-independent methods and screening among culturable plum community for indigenous bacteria active against phytopathogens. METHODS AND RESULTS: The bacterial communities associated with leaves and fruits of four local Serbian plum cultivars (Pozegaca, Ranka, Cacanska Lepotica and Cacanska Rodna) were investigated in two phenological stages during early (May) and late (July) fruit maturation. Metagenomic approach revealed Methylobacterium, Sphingomonas and Hymenobacter as dominant genera. The most frequently isolated representatives with cultivable approach were pseudomonads with Pseudomonas syringae and Pseudomonas graminis, the most likely resident species of plum community. Antagonistic Bacillus thuringiensis R3/3 isolate from plum phyllosphere had ability to produce exoenzymes, reduce the growth of phytopathogenic bacteria in co-culture environment and show quorum quenching activity. CONCLUSIONS: Plum cultivar and growth season contribute to the structure of the bacterial community associated with plum. Plum phyllosphere is good source of antagonists effective against phytopathogens. SIGNIFICANCE AND IMPACT OF STUDY: Knowledge of bacterial communities on plum will have an impact on studies related to phyllosphere ecology and biocontrol. The indigenous antagonistic isolate, B. thuringiensis R3/3, from plum could be further investigated for its potential use in biological control of plum diseases.
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Antibiosis , Bacillus thuringiensis/aislamiento & purificación , Bacillus thuringiensis/fisiología , Enfermedades de las Plantas/microbiología , Prunus domestica/microbiología , Bacillus thuringiensis/clasificación , Bacillus thuringiensis/genética , Hojas de la Planta/microbiología , Pseudomonas/clasificación , Pseudomonas/genética , Pseudomonas/aislamiento & purificación , Pseudomonas/fisiologíaRESUMEN
In this paper, we report the generation of an ultra-sharp asymmetric resonance spectrum through Fano-like interference. This generation is accomplished by weakly coupling a high-quality factor (Q factor) Fabry-Pérot (FP) cavity and a low-Q factor FP cavity through evanescent waves. The high-Q FP cavity is formed by Sagnac loop mirrors, whilst the low-Q one is built by partially transmitting Sagnac loop reflectors. The working principle has been analytically established and numerically modelled by using temporal coupled-mode-theory (CMT), and verified using a prototype device fabricated on the 340 nm silicon-on-insulator (SOI) platform, patterned by deep ultraviolet (DUV) lithography. Pronounced asymmetric resonances with slopes up to 0.77 dB/pm have been successfully measured, which, to the best of our knowledge, is higher than the results reported in state-of-the-art devices in on-chip integrated Si photonic studies. The established theoretical analysis method can provide excellent design guidelines for devices with Fano-like resonances. The design principle can be applied to ultra-sensitive sensing, ultra-high extinction ratio switching, and more applications.
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AIM: Assessment of biological control of Pseudomonas syringae pv. aptata using crude lipopeptide extracts (CLEs) of two Bacillus amyloliquefaciens strains (SS-12.6 and SS-38.4) and one Bacillus pumilus strain (SS-10.7). METHODS AND RESULTS: The minimum inhibitory concentration (MIC) of CLEs and their combinations against the pathogen and potential interaction between the extracts were determined in vitro. The most effective antibacterial activity was achieved with the CLE from B. amyloliquefaciens SS-12.6, with an MIC value of 0·63 mg ml-1 . Interactions between CLE combinations were mostly indifferent. The biocontrol potential of CLEs, mixtures of CLEs, and cell culture of B. amyloliquefaciens SS-12.6 was tested on sugar beet plants inoculated with P. syringae pv. aptata P53. The best result in inhibiting the appearance of tissue necrosis (up to 92%) was achieved with B. amyloliquefaciens SS-12.6 cell culture. CONCLUSION: This work demonstrated significant biocontrol potential of the CLE and cell culture of B. amyloliquefaciens SS-12.6 which successfully suppress leaf spot disease severity on sugar beet plants. SIGNIFICANCE AND IMPACT OF THE STUDY: The findings of biocontrol of sugar beet emerging pathogen will contribute to growers in terms of alternative disease control management. This study represents first assessment of biological control of P. syringae pv. aptata.
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Bacillus amyloliquefaciens/química , Bacillus pumilus/química , Beta vulgaris/microbiología , Lipopéptidos/farmacología , Enfermedades de las Plantas/microbiología , Pseudomonas syringae/efectos de los fármacos , Bacillus amyloliquefaciens/metabolismo , Bacillus pumilus/metabolismo , Lipopéptidos/metabolismo , Pruebas de Sensibilidad Microbiana , Enfermedades de las Plantas/prevención & control , Pseudomonas syringae/fisiologíaRESUMEN
This study aimed to investigate the effects of propofol through evaluating its interaction with nitric oxide (NO), hydrogen sulfide (H2S), and carbon monoxide (CO). Wistar male rats were divided in 4 groups: (1) bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.); (2) Nω-nitro-l-arginine methyl ester (L-NAME; NO synthase inhibitor, 60 mg/kg bw, i.p.) + bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.); (3) DL-propargylglycine (DL-PAG; H2S synthase inhibitor, 50 mg/kg bw, i.p.) + bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.); (4) zinc protoporphyrin IX (ZnPPIX; CO synthase inhibitor, 50 µmol/kg bw, i.p.) + bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.). Increased levels of albumins, low-density lipoproteins, alkaline phosphatase, amylase, high-sensitivity Troponin T, and fibrinogen were found in L-NAME + propofol group. Platelet crit, platelet count, total cholesterol, and high-density lipoproteins were elevated in ZnPPIX + propofol group. Hydrogen peroxide was increased in all groups treated with gasotransmitters inhibitors. Reduced glutathione was reduced in all groups, superoxide dismutase activity only in L-NAME + propofol. The effect of propofol on various biochemical, haematological, and oxidative stress markers may be at least in part mediated through interaction with 3 estimated gasotransmitters.
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Anestésicos/farmacología , Gasotransmisores/antagonistas & inhibidores , Pruebas Hematológicas , Estrés Oxidativo/efectos de los fármacos , Propofol/farmacología , Animales , Biomarcadores/sangre , Hemostasis/efectos de los fármacos , Homocisteína/sangre , Masculino , Ratas , Ratas WistarRESUMEN
Considering the well-known antioxidant properties of statins, it seems important to assess their impact on major markers of oxidative stress (superoxide anion radical, nitric oxide, and index of lipid peroxidation) to compare the antioxidative potentials of atorvastatin and simvastatin during the different degrees of hyperhomocysteinemia (HHcy) in rats. This study was conducted on adult male Wistar albino rats (n = 90; 4 weeks old; 100 ± 15 g body mass) in which HHcy was achieved by dietary manipulation. For 4 weeks, the animals were fed with one of the following diets: standard rodent chow, diet enriched in methionine with no deficiency in B vitamins (folic acid, B6, and B12), or diet enriched in methionine and deficient in B vitamins (folic acid, B6, and B12). At the same time, animals were treated with atorvastatin at doses of 3 mg/kg/day i.p. or simvastatin at doses of 5 mg/kg/day i.p. Levels of superoxide anion radical and TBARS were significantly decreased by administration of simvastatin in normal and high-homocysteine (Hcy) groups (p < 0.05). At 4 weeks after feeding with purified diets, the concentrations of the GSH, CAT, and SOD antioxidants were significantly affected among all groups (p < 0.05). Our results indicated that statin therapy had variable effects on the redox status in hyperhomocysteinemic rats, and simvastatin demonstrated stronger antioxidant effects than did atorvastatin.
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Atorvastatina/farmacología , Dieta/efectos adversos , Estrés Oxidativo/efectos de los fármacos , Simvastatina/farmacología , Animales , Catalasa/sangre , Hiperhomocisteinemia/sangre , Hiperhomocisteinemia/inducido químicamente , Hiperhomocisteinemia/tratamiento farmacológico , Masculino , Ratas , Ratas Wistar , Superóxido Dismutasa/sangre , Superóxidos/sangre , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
Using cultivation-dependant method, we isolated 184 strains from fresh and old bee bread, pollen, larvae and adults of solitary bee Osmia cornuta. The 16S rDNA sequencing of 79 selected isolates gave the final species-specific identification of strains. Phylogenetic analysis indicated that microbiota isolated from five different sources were represented with 29 species within three different phyla, Firmicutes with 25 species, Actinobacteria with only one species and Proteobacteria with three species of Enterobacteriaceae. Bacterial biodiversity presented with Shannon-Wiener index (H') was highest in the alimentary tract of adults and old bee bread (H' = 2.43 and H' = 2.53, respectively) and in the same time no dominance of any species was scored. On the contrary, results obtained for Simpson index (D) showed that in pollen samples the dominant species was Pantoea agglomerans (D = 0.42) while in fresh bee bread that was Staphylococcus sp. (D = 0.27). We assume that microbial diversity detected in the tested samples of solitary bee O. cornuta probably come from environment.
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Bacterias/aislamiento & purificación , Abejas/microbiología , Polen/microbiología , Própolis , Animales , Bacterias/genética , ADN Bacteriano/genética , Genotipo , Larva/microbiologíaRESUMEN
AIM: To isolate and characterize bacteriocin, licheniocin 50.2, from soil bacteria identified as Bacillus licheniformis. METHODS AND RESULTS: The strain B. licheniformis VPS50.2 was identified as bacteriocin producer, effective against Gram-positive bacteria, including Listeria monocytogenes, methicillin-resistant Staphylococcus aureus (MRSA) and ß-haemolytic streptococci. The start of bacteriocin production coincides with the beginning of sporulation. Ammonium sulfate precipitation, chloroform extraction and ultrafiltration were used for bacteriocin purification. MALDI TOF/TOF mass spectrometry of purified sample detected the protein with molecular mass of 3253·209 Da. N-terminal sequencing recognized first 15 amino acids with the sequence: W E E Y N I I X Q L G N K G Q. We named the newly characterized bacteriocin as subclass II.3 bacteriocin, licheniocin 50·2. The bacteriocin activity was insensitive to lysozyme and proteinase K, heat stable after incubation at 100°C for 30 min and over wide range of pH (2-12). MICs of crude bacteriocin extract were determined for L. monocytogenes and MRSA. Time-kill study showed that licheniocin had bactericidal effect to L. monocytogenes. CONCLUSION: A novel, thermostable, pH-tolerant bacteriocin active against Gram-positive bacteria was isolated. SIGNIFICANCE AND IMPACT OF THE STUDY: Attributes of new, stable licheniocin 50.2 make it a promising agent for application as biopreservative in food industry.
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Antibacterianos/biosíntesis , Antibacterianos/farmacología , Bacillus/metabolismo , Bacteriocinas/biosíntesis , Bacteriocinas/farmacología , Antibacterianos/aislamiento & purificación , Bacillus/aislamiento & purificación , Bacteriocinas/aislamiento & purificación , Listeria monocytogenes/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Datos de Secuencia Molecular , Peso Molecular , Microbiología del SueloRESUMEN
OBJECTIVES: We aimed to (1) develop a novel instrument, suitable for the general population, capturing intentional non-adherence (iNAR), consisting of non-adherence to prescribed therapy, self-medication and avoidance of seeking medical treatment; (2) differentiate it from other forms of non-adherence, for example, smoking; and (3) relate iNAR to patient-related factors, such as sociodemographics, health status and endorsement of irrational beliefs (conspiratorial thinking and superstitions) and to healthcare-related beliefs and experiences ((mis)trust and negative experiences with the healthcare system, normalisation of patient passivity). DESIGN: То generate iNAR items, we employed a focus group with medical doctors, supplemented it with a literature search and invited a public health expert to refine it further. We examined the internal structure and predictors of iNAR in an observational study. SETTING: Data were collected online using snowball sampling and social networks. PARTICIPANTS: After excluding those who failed one or more out of three attention checks, the final sample size was n=583 adult Serbian citizens, 74.4% female, mean age 39.01 years (SD=12.10). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary, planned outcome is the iNAR Questionnaire, while smoking was used for comparison purposes. RESULTS: Factor analysis yielded a one-factor solution, and the final 12-item iNAR Questionnaire had satisfactory internal reliability (alpha=0.72). Health condition and healthcare-related variables accounted for 14% of the variance of iNAR behaviours, whereas sociodemographics and irrational beliefs did not additionally contribute. CONCLUSIONS: We constructed a brief yet comprehensive measure of iNAR behaviours and related them to health and sociodemographic variables and irrational beliefs. The findings suggest that public health interventions should attempt to improve patients' experiences with the system and build trust with their healthcare practitioners rather than aim at specific demographic groups or at correcting patients' unfounded beliefs. STUDY REGISTRATION: The design and confirmatory analyses plan were preregistered (https://osf.io/pnugm).
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Atención a la Salud , Estado de Salud , Adulto , Humanos , Femenino , Masculino , Serbia , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
People resort to various questionable health practices to preserve or regain health - they intentionally do not adhere to medical recommendations (e.g. self-medicate or modify the prescribed therapies; iNAR), or use traditional/complementary/alternative (TCAM) medicine. As retrospective reports overestimate adherence and suffer from recall and desirability bias, we tracked the variations in daily questionable health behaviors and compared them to their retrospectively reported lifetime use. We also preregistered and explored their relations to a wide set of psychological predictors - distal (personality traits and basic thinking dispositions) and proximal (different unfounded beliefs and biases grouped under the term irrational mindset). A community sample (N = 224) tracked daily engagement in iNAR and TCAM use for 14 days, resulting in 3136 data points. We observed a high rate of questionable health practices over the 14 days; daily engagement rates roughly corresponded to lifetime ones. Both iNAR and TCAM were weakly, but robustly positively related. Independent of the assessment method, an irrational mindset was the most important predictor of TCAM use. For iNAR, however, psychological predictors emerged as relevant only when assessed retrospectively. Our study offers insight into questionable health behaviors from both a within and between-person perspective and highlights the importance of their psychological roots.
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Ansiedad , Evaluación Ecológica Momentánea , Humanos , Estudios Retrospectivos , Conductas Relacionadas con la Salud , Recuerdo MentalRESUMEN
BACKGROUND: Exposure to hand-arm vibrations is a known cause of the Hand-arm vibration syndrome (HAVS), a progressive syndrome beginning with sensory loss and leading to gangrene, making timely diagnosis essential. OBJECTIVES: Assessment of the usefulness of 9 diagnostic parameters claimed as being of greatest value in the diagnosis of HAVS, and examination of the complementary diagnostic value of the curve shapes. METHODS: Three groups of subjects (HAVS cases, exposed workers without irreversible changes, and controls) were examined by cold provocation followed by thermographic imaging, obtainment of rewarming curves for four preselected regions and calculation of parameters. The discriminative value of individual parameters and the discriminative power of a combination of all the parameters were assessed. Qualitative curve shape analysis was included. RESULTS: The greatest individual discriminative ability is associated with RT (rewarming time to pre-cooling value, p < 0.001), Tmax (maximum temperature during the 10-minute recovery, p < 0.001), k (rewarming rate, p < 0.012) and RD (rewarming delay, p < 0.031). The discriminant analysis yielded one significant discriminant function (Wilks' lambda = 0.278, chi2 (18) = 48.67, p < 0.001, canonical R2 = 0.63). Four types of rewarming curves were identified. CONCLUSIONS: RT, Tmax, k and RD appear to be the most suitable individual parameters for group discrimination. When linearly combined, the parameters can be useful for discriminating HAVS cases from both Controls and Claimants, which constitutes the main task of an occupational health physician. Additional information is available from the qualitative assessment of the rewarming curve shape.
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Frío , Dedos , Síndrome por Vibración de la Mano y el Brazo/diagnóstico , Temperatura Cutánea/fisiología , Termografía , Análisis Discriminante , Femenino , Dedos/irrigación sanguínea , Síndrome por Vibración de la Mano y el Brazo/fisiopatología , Humanos , Masculino , Nervio Mediano/fisiopatología , Angioscopía Microscópica , Uñas/irrigación sanguínea , Conducción Nerviosa , Exposición Profesional , Pletismografía , Factores de Tiempo , Nervio Cubital/fisiopatologíaRESUMEN
BACKGROUND: Pimavanserin is a 5-HT2A receptor inverse agonist/antagonist and is approved in the United States for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis. OBJECTIVE: Evaluate the efficacy of pimavanserin on symptoms of psychosis in patients with Alzheimer's disease (AD). DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Nursing home residents. PARTICIPANTS: Patients with AD psychosis. INTERVENTIONS: Pimavanserin 34 mg or placebo daily for 12 weeks. MEASUREMENTS: The primary endpoint was mean change from baseline at Week 6 on the Neuropsychiatric Inventory-Nursing Home Version psychosis score (NPI-NH-PS). In the prespecified subgroup analysis, the mean change in NPI-NH-PS and the responder rates among those with baseline NPI-NH-PS ≥12 were evaluated. RESULTS: Of 181 patients randomized (n=90 pimavanserin; n=91 placebo), 57 had baseline NPI-NH-PS ≥12 (n=27 pimavanserin; n=30 placebo). In this severe subgroup, large treatment effects were observed (delta=-4.43, Cohen's d=-0.73, p=0.011), and ≥30% improvement was 88.9% vs. 43.3% (p<0.001) and ≥50% improvement was 77.8% vs. 43.3% (p=0.008) for pimavanserin and placebo, respectively. The rate of adverse events (AEs) in the severe subgroup was similar between treatment groups, and urinary tract infection, fall, and agitation were most frequent. Serious AEs was similar with pimavanserin (17.9%) and placebo (16.7%) with fewer discontinuations due to AEs with pimavanserin (7.1%) compared to placebo (10.0%). Minimal change from baseline occurred for the mean MMSE score over 12 weeks. CONCLUSIONS: Pimavanserin demonstrated significant efficacy in AD psychosis in patients with higher baseline severity of psychotic symptoms (NPI-NH-PS ≥12). Treatment with pimavanserin showed an acceptable tolerability profile.
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Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/psicología , Piperidinas/uso terapéutico , Trastornos Psicóticos/complicaciones , Trastornos Psicóticos/tratamiento farmacológico , Urea/análogos & derivados , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/complicaciones , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Casas de Salud , Piperidinas/efectos adversos , Antagonistas del Receptor de Serotonina 5-HT2/efectos adversos , Antagonistas del Receptor de Serotonina 5-HT2/uso terapéutico , Resultado del Tratamiento , Urea/efectos adversos , Urea/uso terapéuticoRESUMEN
Psychosis is common across dementia types with a prevalence of 20% to 70%. Currently, no pharmacologic treatment is approved for dementia-related psychosis. Atypical antipsychotics are frequently used to treat these disorders, despite significant safety concerns. Pimavanserin, a selective 5-HT2A inverse agonist/antagonist, was approved in the U.S. for treating hallucinations and delusions associated with Parkinson's disease psychosis (PDP). Patients in the pimavanserin group experienced a significant (p=0.001) improvement in Scale for the Assessment of Positive Symptoms - Parkinson's disease (SAPS-PD) scores vs. placebo. In a subgroup analysis of patients with cognitive impairment (MMSE score ≥21 but ≤24), the observed improvement on the SAPS-PD with pimavanserin (N=50) was also significant (p=0.002) and larger than in the overall study population without an adverse effect on cognition. In a Phase 2 study with pimavanserin in Alzheimer's disease psychosis, pimavanserin significantly (p=0.045) improved psychosis at Week 6 vs. placebo on the NPI-NH Psychosis Score (PS). In a prespecified subgroup of patients with a baseline NPI-NH PS ≥12, a substantively larger treatment effect (p=0.011) was observed vs. participants with NPI-NH PS <12. The results of these studies in cognitively impaired patients with PDP provided the scientific foundation for an ongoing study of pimavanserin for treating patients with dementia-related psychosis associated with the most common neurodegenerative disorders. The study uses a relapse-prevention design with the endpoint of time-to-relapse of psychosis to evaluate the long-term efficacy and safety of pimavanserin as a potential treatment for hallucinations and delusions of dementia-related psychosis.
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Demencia/complicaciones , Piperidinas/uso terapéutico , Trastornos Psicóticos/tratamiento farmacológico , Antagonistas del Receptor de Serotonina 5-HT2/uso terapéutico , Urea/análogos & derivados , Enfermedad de Alzheimer/complicaciones , Ensayos Clínicos como Asunto , Humanos , Pruebas de Estado Mental y Demencia , Enfermedad de Parkinson/complicaciones , Trastornos Psicóticos/etiología , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Urea/uso terapéuticoRESUMEN
BACKGROUND: Although urea kinetic modeling indices for measuring dialysis dose are recommended by world expert groups, it is not quite clear whether some of these are superior in predicting the outcome over others. This prospective, single-center study was carried out with the aim to compare predictive value of different indices and methods of measuring dialysis dose. METHODS: The analysis included 93 anuric patients having been on hemodialysis for at least 2 years who were followed-up for 75-months. The dialysis dose was measured by Kt/V (formal UKM, 3 and 2 urea samples), Kt/V (Daugirdas), Kt/V (Lowrie), eKt/V (Daugirdas), URR and TAC urea. RESULTS: Correlations between dialysis indices and survival time were significant for all indices (p<0.01) except for TAC. All indices, except for TAC urea, were significant predictors of mortality (multivariate Cox regression analysis; p<0.01) and differences of significant levels among these colinear parameters were small. CONCLUSION: All examined indices except for TAC urea were highly predictive of patient mortality. Daugirdas and Lowrie simplified Kt/V indices are as predictive of all-cause mortality as more complex formal UKM methods in long-term patients on a 3x4h/week schedule.
Asunto(s)
Anuria/mortalidad , Soluciones para Hemodiálisis/administración & dosificación , Modelos Biológicos , Diálisis Renal/métodos , Adulto , Factores de Edad , Anciano , Anuria/terapia , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Fósforo/metabolismo , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Análisis de Supervivencia , Urea/metabolismo , Yugoslavia/epidemiologíaRESUMEN
We have demonstrated a bidirectional wavelength division (de)multiplexer (WDM) on the silicon-on-insulator platform using two 4-channel angled multimode interferometers (AMMIs) sharing the same multimode interference waveguide. An excellent match of the peak transmission wavelength of each channel between the two AMMIs was achieved. The input and output access waveguides were arranged in a configuration such that the propagation of light of one AMMI in the multimode interference waveguide suffered minimal perturbation by the input and output waveguides of the other AMMI. This type of device is ideal for the WDM system for datacom or telecom applications, e.g. an integrated optical transceiver, where the transmission wavelengths are required to match with the receiving wavelengths. The device also benefits from simple fabrication (as only a single lithography and etching step is required), improved convenience for the transceiver layout design, a reduction in tuning power and circuitry and efficient use of layout space. A low insertion loss of 3-4 dB, and low crosstalk of -15 to -20 dB, was achieved.
RESUMEN
In the presence of catalytic amounts of MTO, methyltrioxorhenium, methyl trimethylsilyl ketene acetals are oxidized with urea hydrogen peroxide to afford alpha-hydroxy and alpha-siloxy esters. On treatment with potassium fluoride, the alpha-hydroxy esters are obtained in high yields.