Ensemble of global climate simulations for temperature in historical, 1.5 °C and 2.0 °C scenarios from HadAM4.

Large ensembles of global temperature are provided for three climate scenarios: historical (2006-16), 1.5 °C and 2.0 °C above pre-industrial levels. Each scenario has 700 members (70 simulations per year for ten years) of 6-hourly mean temperatures at a resolution of 0.833° ´ 0.556° (longitude ´ latitude) over the land surface. The data was generated using the climateprediction.net (CPDN) climate simulation environment, to run HadAM4 Atmosphere-only General Circulation Model (AGCM) from the UK Met Office Hadley Centre. Biases in simulated temperature were identified and corrected using quantile mapping with reference temperature data from ERA5. The data is stored within the UK Natural and Environmental Research Council Centre for Environmental Data Analysis repository as NetCDF V4 files.

TNFR1-mediated neuroinflammation is necessary for respiratory deficits observed in 6-hydroxydopamine mouse model of Parkinsons Disease.

Parkinson's Disease (PD) is characterized by classic motor symptoms related to movement, but PD patients can experience symptoms associated with impaired autonomic function, such as respiratory disturbances. Functional respiratory deficits are known to be associated with brainstem neurodegeneration in the mice model of PD induced by 6-hydroxydopamine (6-OHDA). Understanding the causes of neuronal death is essential for identifying specific targets to prevent degeneration. Many mechanisms can explain why neurons die in PD, and neuroinflammation is one of them. To test the influence of inflammation, mediated by microglia and astrocytes cells, in the respiratory disturbances associated with brainstem neurons death, we submitted wild-type (WT) and TNF receptor 1 (TNFR1) knockout male mice to the 6-OHDA model of PD. Also, male C57BL/6 animals were induced using the same PD model and treated with minocycline (45 mg/kg), a tetracycline antibiotic with anti-inflammatory properties. We show that degeneration of brainstem areas such as the retrotrapezoid nucleus (RTN) and the pre-Botzinger Complex (preBotC) were prevented in both protocols. Notably, respiratory disturbances were no longer observed in the animals where inflammation was suppressed. Thus, the data demonstrate that inflammation is responsible for the breathing impairment in the 6-OHDA-induced PD mouse model.

Intraspecific variation of long bone cross-sectional properties in Pan troglodytes troglodytes and Gorilla gorilla gorilla.

OBJECTIVES: Morphological intraspecific variation is due to the balance between skeletal plasticity and genetic constraint on the skeleton. Osteogenic responses to external stimuli, such as locomotion, have been well documented interspecifically across the primate order, but less so at the intraspecific level. Here, we examine the differences in cross-sectional variability of the femur, humerus, radius, and tibia in Pan troglodytes troglodytes versus Gorilla gorilla gorilla. We investigate whether there are sex, species, bone, and trait differences in response to variable body size and locomotion. MATERIALS AND METHODS: Adult male and female P. t. troglodytes and G. g. gorilla long bones from the Cleveland Museum of Natural History were scanned with a peripheral quantitative computer tomography system. Scans were taken at the midshaft of each bone according to functional bone length. Coefficients of variation were used to provide a size-independent measure of variation. We applied a Bonferroni correction to account for the multiple pairwise tests. RESULTS: There were limited significant differences between males and females, however, females tended to be more variable than males. Variation in Gorilla, when significant, was greater than in Pan, although significant differences were limited. There were no differences between bone variability in male and female Gorilla, and female Pan. DISCUSSION: Increased female variability may be due to more variable locomotor behavior, particularly during periods of pregnancy, lactation, and caring for an offspring compared to consistent locomotion over the life course by males. Body size may be a contributing factor to variability; more work is needed to understand this relationship.

Retrospective assessment of the impact of an education specialist on the care of children with hearing loss.

OBJECTIVE: To assess the impact of an education specialist in a multidisciplinary pediatric hearing loss clinic. STUDY DESIGN: Retrospective review and cross-sectional survey. SETTING: Single tertiary care center. METHODS: Consultations held between an education specialist and families of pediatric deaf or hard of hearing (DHH) children within a two-year period were reviewed. Reasons for referral and services provided to each patient and family who subsequently worked with the educational specialist were assessed. Parents of patients who had previously worked with the education specialist were invited to complete a survey evaluating their experience. RESULTS: 102 patients were referred to the educational specialist in a two-year period. Most common reasons for referral included need for special education plans to accommodate their hearing deficit (32) or family request to support for revisions to such plans (37). 14 patient families completed our survey. 76.9 % of respondents confirmed that the education specialist recommended resources they had not been introduced to before. Given a scale of 1 ("completely dissatisfied") and 10 being "completely satisfied," the average rating of the 14 respondents was 9.0. CONCLUSION: The role of an education specialist in a pediatric hearing loss clinic is to optimize patient and family access to resources that could benefit their DHH child's academic development over time. Future studies should prospectively investigate the impact of education specialist services on the educational progress of DHH patients compared to outcomes without these supports.

The Pedunculopontine Tegmental Nucleus is not Important for Breathing Impairments Observed in a Parkinson's Disease Model.

Parkinson's disease (PD) is a motor disorder resulting from degeneration of dopaminergic neurons of substantia nigra pars compacta (SNpc), with classical and non-classical symptoms such as respiratory instability. An important region for breathing control, the Pedunculopontine Tegmental Nucleus (PPTg), is composed of cholinergic, glutamatergic, and GABAergic neurons. We hypothesize that degenerated PPTg neurons in a PD model contribute to the blunted respiratory activity. Adult mice (40 males and 29 females) that express the fluorescent green protein in cholinergic, glutamatergic or GABAergic cells were used (Chat-cre Ai6, Vglut2-cre Ai6 and Vgat-cre Ai6) and received bilateral intrastriatal injections of vehicle or 6-hydroxydopamine (6-OHDA). Ten days later, the animals were exposed to hypercapnia or hypoxia to activate PPTg neurons. Vglut2-cre Ai6 animals also received retrograde tracer injections (cholera toxin b) into the retrotrapezoid nucleus (RTN) or preBötzinger Complex (preBötC) and anterograde tracer injections (AAV-mCherry) into the SNpc. In 6-OHDA-injected mice, there is a 77% reduction in the number of dopaminergic neurons in SNpc without changing the number of neurons in the PPTg. Hypercapnia activated fewer Vglut2 neurons in PD, and hypoxia did not activate PPTg neurons. PPTg neurons do not input RTN or preBötC regions but receive projections from SNpc. Although our results did not show a reduction in the number of glutamatergic neurons in PPTg, we observed a reduction in the number of neurons activated by hypercapnia in the PD animal model, suggesting that PPTg may participate in the hypercapnia ventilatory response.

AAV-mediated interneuron-specific gene replacement for Dravet syndrome.

Dravet syndrome (DS) is a devastating developmental epileptic encephalopathy marked by treatment-resistant seizures, developmental delay, intellectual disability, motor deficits, and a 10-20% rate of premature death. Most DS patients harbor loss-of-function mutations in one copy of SCN1A , which has been associated with inhibitory neuron dysfunction. Here we developed an interneuron-targeting AAV human SCN1A gene replacement therapy using cell class-specific enhancers. We generated a split-intein fusion form of SCN1A to circumvent AAV packaging limitations and deliver SCN1A via a dual vector approach using cell class-specific enhancers. These constructs produced full-length Na V 1.1 protein and functional sodium channels in HEK293 cells and in brain cells in vivo . After packaging these vectors into enhancer-AAVs and administering to mice, immunohistochemical analyses showed telencephalic GABAergic interneuron-specific and dose-dependent transgene biodistribution. These vectors conferred strong dose-dependent protection against postnatal mortality and seizures in two DS mouse models carrying independent loss-of-function alleles of Scn1a, at two independent research sites, supporting the robustness of this approach. No mortality or toxicity was observed in wild-type mice injected with single vectors expressing either the N-terminal or C-terminal halves of SCN1A , or the dual vector system targeting interneurons. In contrast, nonselective neuronal targeting of SCN1A conferred less rescue against mortality and presented substantial preweaning lethality. These findings demonstrate proof-of-concept that interneuron-specific AAV-mediated SCN1A gene replacement is sufficient for significant rescue in DS mouse models and suggest it could be an effective therapeutic approach for patients with DS.

Electrospun Poly(acrylic acid-co-4-styrene sulfonate) as Potential Drug-Eluting Scaffolds for Targeted Chemotherapeutic Delivery Systems on Gastric (AGS) and Breast (MDA-Mb-231) Cancer Cell Lines.

Potential drug-eluting scaffolds of electrospun poly(acrylic acid-co-styrene sulfonate) P(AA-co-SS) in clonogenic assays using tumorigenic gastric and ovarian cancer cells were tested in vitro. Electrospun polymer nanofiber (EPnF) meshes of PAA and PSSNa homo- and P(AA-co-SS) copolymer composed of 30:70, 50:50, 70:30 acrylic acid (AA) and sodium 4-styrene sulfonate (SSNa) units were performed by electrospinning (ES). The synthesis, structural and morphological characterization of all EPnF meshes were analyzed by optical and electron microscopy (SEM-EDS), infrared spectroscopy (FTIR), contact angle, and X-ray diffraction (XRD) measurements. This study shows that different ratio of AA and SSNa of monomers in P(AA-co-SS) EPnF play a crucial role in clonogenic in vitro assays. We found that 50:50 P(AA-co-SS) EPnF mesh loaded with antineoplastic drugs can be an excellent suppressor of growth-independent anchored capacities in vitro assays and a good subcutaneous drug delivery system for chemotherapeutic medication in vivo model for surgical resection procedures in cancer research.

Regulation of blood vessels by ATP in the ventral medullary surface in a rat model of Parkinson's disease.

Parkinson's disease (PD) patients often experience impairment of autonomic and respiratory functions. These include conditions such as orthostatic hypotension and sleep apnea, which are highly correlated with dysfunctional central chemoreception. Blood flow is a fundamental determinant of tissue CO2/H+, yet the extent to which blood flow regulation within chemoreceptor regions contributes to respiratory behavior during neurological disease remains unknown. Here, we tested the hypothesis that 6-hydroxydopamine injection to inducing a known model of PD results in dysfunctional vascular homeostasis, biochemical dysregulation, and glial morphology of the ventral medullary surface (VMS). We show that hypercapnia (FiCO2 = 10%) induced elevated VMS pial vessel constriction in PD animals through a P2-receptor dependent mechanism. Similarly, we found a greater CO2-induced vascular constriction after ARL67156 (an ectonucleotidase inhibitor) in control and PD-induced animals. In addition, we also report that weighted gene correlational network analysis of the proteomic data showed a protein expression module differentially represented between both groups. This module showed that gene ontology enrichment for components of the ATP machinery were reduced in our PD-model compared to control animals. Altogether, our data indicate that dysfunction in purinergic signaling, potentially through altered ATP bioavailability in the VMS region, may compromise the RTN neuroglial vascular unit in a PD animal model.

Interaction of obesity polygenic score with lifestyle risk factors in an electronic health record biobank.

BACKGROUND: Genetic and lifestyle factors have considerable effects on obesity and related diseases, yet their effects in a clinical cohort are unknown. This study in a patient biobank examined associations of a BMI polygenic risk score (PRS), and its interactions with lifestyle risk factors, with clinically measured BMI and clinical phenotypes. METHODS: The Mass General Brigham (MGB) Biobank is a hospital-based cohort with electronic health record, genetic, and lifestyle data. A PRS for obesity was generated using 97 genetic variants for BMI. An obesity lifestyle risk index using survey responses to obesogenic lifestyle risk factors (alcohol, education, exercise, sleep, smoking, and shift work) was used to dichotomize the cohort into high and low obesogenic index based on the population median. Height and weight were measured at a clinical visit. Multivariable linear cross-sectional associations of the PRS with BMI and interactions with the obesity lifestyle risk index were conducted. In phenome-wide association analyses (PheWAS), similar logistic models were conducted for 675 disease outcomes derived from billing codes. RESULTS: Thirty-three thousand five hundred eleven patients were analyzed (53.1% female; age 60.0 years; BMI 28.3 kg/m2), of which 17,040 completed the lifestyle survey (57.5% female; age: 60.2; BMI: 28.1 (6.2) kg/m2). Each standard deviation increment in the PRS was associated with 0.83 kg/m2 unit increase in BMI (95% confidence interval (CI) =0.76, 0.90). There was an interaction between the obesity PRS and obesity lifestyle risk index on BMI. The difference in BMI between those with a high and low obesogenic index was 3.18 kg/m2 in patients in the highest decile of PRS, whereas that difference was only 1.55 kg/m2 in patients in the lowest decile of PRS. In PheWAS, the obesity PRS was associated with 40 diseases spanning endocrine/metabolic, circulatory, and 8 other disease groups. No interactions were evident between the PRS and the index on disease outcomes. CONCLUSIONS: In this hospital-based clinical biobank, obesity risk conferred by common genetic variants was associated with elevated BMI and this risk was attenuated by a healthier patient lifestyle. Continued consideration of the role of lifestyle in the context of genetic predisposition in healthcare settings is necessary to quantify the extent to which modifiable lifestyle risk factors may moderate genetic predisposition and inform clinical action to achieve personalized medicine.

Respiratory disorders of Parkinson's disease.

Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra, mainly affecting people over 60 yr of age. Patients develop both classic symptoms (tremors, muscle rigidity, bradykinesia, and postural instability) and nonclassical symptoms (orthostatic hypotension, neuropsychiatric deficiency, sleep disturbances, and respiratory disorders). Thus, patients with PD can have a significantly impaired quality of life, especially when they do not have multimodality therapeutic follow-up. The respiratory alterations associated with this syndrome are the main cause of mortality in PD. They can be classified as peripheral when caused by disorders of the upper airways or muscles involved in breathing and as central when triggered by functional deficits of important neurons located in the brainstem involved in respiratory control. Currently, there is little research describing these disorders, and therefore, there is no well-established knowledge about the subject, making the treatment of patients with respiratory symptoms difficult. In this review, the history of the pathology and data about the respiratory changes in PD obtained thus far will be addressed.

Synergistic Effect of Composite Nickel Phosphide Nanoparticles and Carbon Fiber on the Enhancement of Salivary Enzyme-Free Glucose Sensing.

An electrospinning method was used for the preparation of an in situ composite based on Ni2P nanoparticles and carbon fiber (FC). The material was tested for the first time against direct glucose oxidation reaction. The Ni2P nanoparticles were distributed homogeneously throughout the carbon fibers with a composition determined by thermogravimetric analysis (TGA) of 40 wt% Ni2P and 60 wt% carbon fiber without impurities in the sample. The electrochemical measurement results indicate that the GCE/FC/Ni2P in situ sensor exhibits excellent catalytic activity compared to the GCE/Ni2P and GCE/FC/Ni2P ex situ electrodes. The GCE/FC/Ni2P in situ sensor presents a sensitivity of 1050 µAmM-1cm-2 in the range of 5-208 µM and a detection limit of 0.25 µM. The sensor was applied for glucose detection in artificial saliva, with a low interference observed from normally coexisting electroactive species. In conclusion, our sensor represents a novel and analytical competitive alternative for the development of non-enzymatic glucose sensors in the future.

Duration of neonatal intensive care unit exposure associated with decreased risk of atopic dermatitis.

BACKGROUND/OBJECTIVES: Premature infants have lower rates of atopic dermatitis (AD) compared with full-term infants, though little is known about the factors contributing to this association. We explored the infant and environmental factors that may contribute to the association between prematurity and atopic dermatitis, including mode of delivery, birthweight, gestation, and duration of stay in the neonatal intensive care unit (NICU). METHODS: This was a single-center retrospective study. Independent samples t tests or chi-square tests were used to compare groups on continuous and categorical variables, respectively. Logistic regression then examined the association of the predictor variables with AD. RESULTS: Four thousand sixteen mother-infant dyads were included. Infants had a higher risk of developing AD if they were delivered vaginally (P = .013), did not stay in the NICU (P < .001), had a longer gestation (P = .001), or had a higher birthweight (P = .002). In modeling atopic dermatitis with the predictor variables, only NICU length of stay remained significantly associated with a lower risk of AD (P = .004). CONCLUSION: Infants had a lower risk of developing AD if they had a longer stay in the NICU.

Activity and Exercise Intolerance After Concussion: Identification and Management of Postural Orthostatic Tachycardia Syndrome.

BACKGROUND AND PURPOSE: Postural orthostatic tachycardia syndrome (POTS) is increasingly recognized as a complication affecting recovery from concussion. Individuals with POTS demonstrate refractory dizziness, lightheadedness, cognitive dysfunction, fatigue, headache, chronic pain, nausea and gastrointestinal dysmotility, activity and exercise intolerance, syncope, and tachycardia. Subtypes of POTS may include hypovolemia, hyperadrenergic states, autonomic neuropathy, and underlying autoimmunity, which may variably impact response to rehabilitation in varying ways. The subtle presentation of POTS postconcussion is often mistaken for underlying anxiety, conversion disorder, or lack of motivation for recovery. This article will present clinical features of POTS that may arise after concussion, and propose a role for physical therapists in the diagnosis and management of POTS during concussion recovery. SUMMARY OF KEY POINTS: Data recorded and entered into a database during clinic visits from a large pediatric institution indicate that 11.4% of individuals diagnosed with POTS report onset of symptoms within 3 months of sustaining a concussion. Activation of the sympathetic nervous system can result in lightheadedness, shortness of breath, chest pain, tachycardia, palpitations on standing or with exertion, and activity and exercise intolerance. Identified comorbidities in people with POTS such as joint hypermobility and autoimmune disorders can further influence recovery. RECOMMENDATIONS FOR CLINICAL PRACTICE: Physical therapists may identify signs and symptoms of POTS in a subset of individuals who remain refractory to typical interventions and who exhibit symptom exacerbation with orthostatic activity. Incorporation of an individualized POTS exercise program into current established concussion interventions may be useful, with emphasis on initial recumbent exercises and ongoing physical therapy assessment of exercise tolerance for dosing of activity intensity and duration.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A211).

Flegmón cervical, ¿Enfermedad de Kawasaki?: a propósito de un caso / Cervical phlegmon, Kawasaki disease? Regarding a clinical case

La enfermedad de Kawasaki es una vasculitis sistémica de etiología aún desconocida.Afecta principalmente a niñosmenores de 5 años y se considera una enfermedad rara, sin tener una prueba diagnóstica específica, siendo diagnosticada con el cumplimiento de una serie de criterios establecidos por la SociedadAmericana de Cardiología. Por otra parte, existe también la presentación atípica de esta enfermedad dificultando aún más su diagnóstico. A continuación, se presenta el caso de una paciente de 8 años que debutó de forma abrupta con fiebre intermitente asociado a impotencia funcional cervical sin otros hallazgos al examen físico, destacando en imágenes compromiso flegmonoso cervical, evolucionando tórpidamente con fiebre prolongada e intermitente y disminución de la lesión flegmonosa asociada a una serie de signos y síntomas, que finalmente pudieron ser agrupados diagnosticándose una enfermedad de Kawasaki. Lo anterior confirma la gran variabilidad en la manifestación de esta enfermedad y refuerza la idea de la dificultad diagnóstica que enfrenta elmédico ante estos casos, a la vez que invita a tenerpresentela sospechadiagnósticaen pacientescon aparentescuadrosinfecciososde evoluciónatípica.

Kawasaki disease is a systemic vasculitis of unknown etiology. It affectsmainly the under-fives, is considered rare and has no specific diagnostic test but rather is diagnosed through fulfilling diagnostic criteria set down by the American Cardiology Society. Atypical presentations of the disease further complicate its diagnosis. Wepresent the case of an eight year old presenting with sudden intermittent fever and functional impairment of the neck with no other physical signs. Images showed a cervical phlegmon. The patient responded poorly with prolonged intermittent fever. As the phlegmon slowly reduced in size a number of signs and symptoms appeared which finally fulfilled the diagnostic criteria for Kawasaki´s disease. This confirms the great variability in the manifestation of this disease, reinforcing the diagnostic difficulty facing the clinician in these cases and at the same time underlines the importance of keeping the disease in mind when faced by apparent infectionswith poor response to treatment.

Percepção de estudantes de Odontologia sobre metodologias ativas no processo de ensino-aprendizagem / Undergraduate dental students' perceptions regarding active methodologies in the teaching-learning process

O objetivo do estudo foi avaliar a percepção dos graduandos em Odontologia da Faculdade de Ciências Médicas e da Saúde de Juiz de Fora (SUPREMA) frente à utilização da articulação interdisciplinar e do portfólio no processo de ensino-aprendizagem. Trata-se de estudo observacional e transversal. Foram avaliados 160 estudantes selecionados aleatoriamente, 20 de cada período, os quais responderam a um questionário. Dos participantes incluídos na pesquisa, 82% (130) eram do gênero feminino e 18% (29) do masculino; 64% (102) dos participantes concordaram totalmente e 30% (47) concordaram parcialmente que a metodologia da articulação interdisciplinar contribuiu para o desenvolvimento da capacidade de aprender e atualizar conhecimentos de forma autônoma. Em relação ao portfólio, 89% (88) dos estudantes do quarto ao oitavo período concordaram totalmente que houve maior estímulo para aperfeiçoar o seu desempenho ao receber conceito suficiente no portfólio e/ou comentários elogiosos; nenhum aluno discordou. Em conclusão, os acadêmicos possuem uma visão favorável quanto à utilização da articulação interdisciplinar e do portfólio clínico. Entretanto, o oitavo período foi o que mais concordou parcialmente e/ou discordou de questões formuladas sobre essas metodologias. O sentimento de não estarem plenamente capacitados para o exercício profissional, sem o respaldo do professor é uma preocupação dos alunos do último período do curso. Isso pode explicar, em parte, os resultados obtidos pelos participantes do oitavo período (AU).

The recent process of teaching and learning involves active and more autonomous participation of the students. Therefore, the student is able to achieve technical excellence associated to critical reasoning. This study aimed to evaluate the perception of the students in Dentistry, of the Faculdade de Ciências Médicas e Saúde de Juiz de Fora (SUPREMA), facing the use of multidisciplinary articulation and portfolio in the teaching-learning process. This is an observational and transversal study, in which 160 students were evaluated, 20 of each semester were randomly selected and answers obtained through the proposed questionnaire. 82% (130) of the participants included in the research were women and 18% (29) were men. 64% (102) of the participants totally agree and 30% (47) partially agree that the multidisciplinary articulation contributed in order to increase the capability of communication in both oral and written forms. About the portfolio, 89% (88) of the students, from the fourth to the eighth semesters, totally agreed that there was greater incentive to improve their development when they received enough in the portfolio and/or rave reviews; none of the students disagreed. In conclusion, it was possible to notice that the students have a satisfactory vision about the use of both the multidisciplinary articulation and the clinical portfolio. However, generally, the students of the eighth semester were the ones who agreed the most partially and/or disagreed about some questions on this methodology. One cause of concern of the last period students of undergraduate courses may be the feeling of not being fully prepared for professional practice without the teacher's support. This may explain, in part, the results obtained in this study by the participants of the eighth period (AU).

Morris Water Maze Test: Optimization for Mouse Strain and Testing Environment.

The Morris water maze (MWM) is a commonly used task to assess hippocampal-dependent spatial learning and memory in transgenic mouse models of disease, including neurocognitive disorders such as Alzheimer's disease. However, the background strain of the mouse model used can have a substantial effect on the observed behavioral phenotype, with some strains exhibiting superior learning ability relative to others. To ensure differences between transgene negative and transgene positive mice can be detected, identification of a training procedure sensitive to the background strain is essential. Failure to tailor the MWM protocol to the background strain of the mouse model may lead to under- or over- training, thereby masking group differences in probe trials. Here, a MWM protocol tailored for use with the F1 FVB/N x 129S6 background is described. This is a frequently used background strain to study the age-dependent effects of mutant P301L tau (rTg(TauP301L)4510 mice) on the memory deficits associated with Alzheimer's disease. Also described is a strategy to re-optimize, as dictated by the particular testing environment utilized.

Meta-analysis of greenhouse gas emissions from anaerobic digestion processes in dairy farms.

This meta-analysis quantifies the changes in greenhouse gas (GHG) emissions from dairy farms, caused by anaerobically digesting (AD) cattle manure. As this is a novel quantifiable synthesis of the literature, a database of GHG emissions from dairy farms is created. Each case in the database consists of a baseline (reference with no AD system) and an AD scenario. To enable interstudy comparison, emissions are normalized by calculating relative changes (RCs). The distributions of RCs are reported by specific GHGs and operation units. Nonparametric tests are applied to the RCs in order to identify a statistical difference of AD with respect to baseline scenarios (Wilcoxon rank test), correlations (Spearman test), and best estimation for changes in emissions (Kernel density distribution estimator). From 749 studies identified, 30 papers yield 89 independent cases. The median reductions in emissions from the baseline scenarios, according to operation units, are -43.2% (n.s.) for storage, -6.3% for field application of slurries, -11.0% for offset of energy from fossil fuel, and +0.4% (n.s.) for offset of inorganic fertilizers. The leaks from digesters are found to significantly increase the emissions from baseline scenarios (median = +1.4%).

Pharmacokinetics of selected chiral flavonoids: hesperetin, naringenin and eriodictyol in rats and their content in fruit juices.

The majority of pharmacokinetic studies of individual flavonoids or after ingestion of foodstuffs have overlooked the chirality of some of these xenobiotics. In order to characterize for the first time the stereoselective pharmacokinetics of three flavonoids, hesperetin, naringenin and eriodictyol were intravenously administered (20 mg/kg) to male Sprague-Dawley rats, and their stereospecific content was assessed in various fruit juices. Concentrations in serum, urine and fruit juices were characterized via HPLC and verified by LC/MS. Short half-lives (3-7 h) in serum were observed, while a better estimation of half-life (12-48 h) and the other pharmacokinetic parameters was observed using urinary data. The three flavonoids are predominantly excreted via non-renal routes (fe values of 3-7%), and undergo rapid and extensive phase II metabolism. The (2S)-epimers of the flavonoid glycosides and the S(-)-enantiomers of the aglycones were predominant and in some instances the organic fruit juices had higher concentrations than the conventional fruit juices. This study reports for the first time the stereospecific pharmacokinetics of three chiral flavonoids and their stereospecific content in fruit juices. It also reports for the first time the stereospecific pharmacokinetics of flavonoids employing urine as a more reliable biological matrix.

Stereospecific high-performance liquid chromatographic analysis of eriodictyol in urine.

A stereospecific method of analysis of eriodictyol [5,7,3',4'-tetrahydroxyflavanone] in biological fluids is necessary to study the kinetics of in vitro and in vivo metabolism, and tissue distribution in fruits and humans. A simple high-performance liquid chromatographic method was developed for the stereospecific determination of eriodictyol in rat and human urine. Separation was achieved on a Chiralpak OJ-RH column with UV detection at 288 nm. The stereospecific calibration curves were linear ranging from 0.5 to 100 microg/ml. The mean extraction efficiency was >98.8%. Precision of the assay was <15% (CV), and was within 12% at the limit of quantitation (0.5 microg/ml). Bias of the assay was lower than 8%, and was within 6% at the limit of quantitation. The assay was applied successfully to the urinary excretion of eriodictyol in rats and humans, and to the stereospecific quantification of eriodictyol in raw lemon juice, conventional and organic lemonade.