ABSTRACT
Widespread gas venting along the Cascadia margin is investigated from acoustic water column data and reveals a nonuniform regional distribution of over 1100 mapped acoustic flares. The highest number of flares occurs on the shelf, and the highest flare density is seen around the nutrition-rich outflow of the Juan de Fuca Strait. We determine â¼430 flow-rates at â¼340 individual flare locations along the margin with instantaneous in situ values ranging from â¼6 mL min-1 to â¼18 L min-1. Applying a tidal-modulation model, a depth-dependent methane density, and extrapolating these results across the margin using two normalization techniques yields a combined average in situ flow-rate of â¼88 × 106 kg y-1. The average methane flux-rate for the Cascadia margin is thus estimated to â¼0.9 g y-1m-2. Combined uncertainties result in a range of these values between 4.5 and 1800% of the estimated mean values.
ABSTRACT
Methane seepage from the upper continental slopes of Western Svalbard has previously been attributed to gas hydrate dissociation induced by anthropogenic warming of ambient bottom waters. Here we show that sediment cores drilled off Prins Karls Foreland contain freshwater from dissociating hydrates. However, our modeling indicates that the observed pore water freshening began around 8 ka BP when the rate of isostatic uplift outpaced eustatic sea-level rise. The resultant local shallowing and lowering of hydrostatic pressure forced gas hydrate dissociation and dissolved chloride depletions consistent with our geochemical analysis. Hence, we propose that hydrate dissociation was triggered by postglacial isostatic rebound rather than anthropogenic warming. Furthermore, we show that methane fluxes from dissociating hydrates were considerably smaller than present methane seepage rates implying that gas hydrates were not a major source of methane to the oceans, but rather acted as a dynamic seal, regulating methane release from deep geological reservoirs.
ABSTRACT
InGaN/GaN nanowire heterostructures are presented as nanophotonic probes for the light-triggered photoelectrochemical detection of NADH. We demonstrate that photogenerated electron-hole pairs give rise to a stable anodic photocurrent whose potential- and pH-dependences exhibit broad applicability. In addition, the simultaneous measurement of the photoluminescence provides an additional tool for the analysis and evaluation of light-triggered reaction processes at the nanostructured interface. InGaN/GaN nanowire ensembles can be excited over a wide wavelength range, which avoids interferences of the photoelectrochemical response by absorption properties of the compounds to be analyzed by adjusting the excitation wavelength. The photocurrent of the nanostructures shows an NADH-dependent magnitude. The anodic current increases with rising analyte concentration in a range from 5µM to 10mM, at a comparatively low potential of 0mV vs. Ag/AgCl. Here, the InGaN/GaN nanowires reach high sensitivities of up to 91µAmM-1cm-2 (in the linear range) and provide a good reusability for repetitive NADH detection. These results demonstrate the potential of InGaN/GaN nanowire heterostructures for the defined conversion of this analyte paving the way for the realization of light-switchable sensors for the analyte or biosensors by combination with NADH producing enzymes.
Subject(s)
Biosensing Techniques/methods , NAD/isolation & purification , Nanowires/chemistry , Gallium/chemistry , Indium/chemistry , NAD/chemistry , Nanostructures/chemistryABSTRACT
The combination of the biocatalytic features of enzymes with the unique physical properties of nanoparticles in a biohybrid system provides a promising approach for the development of advanced bioelectrocatalytic devices. This study describes the construction of photoelectrochemical signal chains based on CdSe/ZnS quantum dot (QD) modified gold electrodes as light switchable elements, and low molecular weight redox molecules for the combination with different biocatalysts. Photoelectrochemical and photoluminescence experiments verify that electron transfer can be achieved between the redox molecules hexacyanoferrate and ferrocene, and the QDs under illumination. Since for both redox mediators a concentration dependent photocurrent change has been found, light switchable enzymatic signal chains are built up with fructose dehydrogenase (FDH) and pyrroloquinoline quinone-dependent glucose dehydrogenase ((PQQ)GDH) for the detection of sugars. After immobilization of the enzymes at the QD electrode the biocatalytic oxidation of the substrates can be followed by conversion of the redox mediator in solution and subsequent detection at the QD electrode. Furthermore, (PQQ)GDH has been assembled together with ferrocenecarboxylic acid on top of the QD electrode for the construction of a funtional biohybrid architecture, showing that electron transfer can be realized from the enzyme over the redox mediator to the QDs and subsequently to the electrode in a completely immobilized fashion. The results obtained here do not only provide the basis for light-switchable biosensing and bioelectrocatalytic applications, but may also open the way for self-driven point-of-care systems by combination with solar cell approaches (power generation at the QD electrode by enzymatic substrate consumption).
Subject(s)
Carbohydrate Dehydrogenases/metabolism , Fructose/metabolism , Glucose Dehydrogenases/metabolism , Glucose/metabolism , Quantum Dots , NanoparticlesABSTRACT
BACKGROUND: Patients with psychosis display the so-called 'Jumping to Conclusions' bias (JTC) - a tendency for hasty decision-making in probabilistic reasoning tasks. So far, only a few studies have evaluated the JTC bias in 'at-risk mental state' (ARMS) patients, specifically in ARMS samples fulfilling 'ultra-high risk' (UHR) criteria, thus not allowing for comparisons between different ARMS subgroups. METHOD: In the framework of the PREVENT (secondary prevention of schizophrenia) study, a JTC task was applied to 188 patients either fulfilling UHR criteria or presenting with cognitive basic symptoms (BS). Similar data were available for 30 healthy control participants matched for age, gender, education and premorbid verbal intelligence. ARMS patients were identified by the Structured Interview for Prodromal Symptoms (SIPS) and the Schizophrenia Proneness Instrument - Adult Version (SPI-A). RESULTS: The mean number of draws to decision (DTD) significantly differed between ARM -subgroups: UHR patients made significantly less draws to make a decision than ARMS patients with only cognitive BS. Furthermore, UHR patients tended to fulfil behavioural criteria for JTC more often than BS patients. In a secondary analysis, ARMS patients were much hastier in their decision-making than controls. In patients, DTD was moderately associated with positive and negative symptoms as well as disorganization and excitement. CONCLUSIONS: Our data indicate an enhanced JTC bias in the UHR group compared to ARMS patients with only cognitive BS. This underscores the importance of reasoning deficits within cognitive theories of the developing psychosis. Interactions with the liability to psychotic transitions and therapeutic interventions should be unravelled in longitudinal studies.
Subject(s)
Cognitive Dysfunction/physiopathology , Decision Making/physiology , Schizophrenia/physiopathology , Adult , Female , Humans , Male , Middle Aged , Risk , Young AdultABSTRACT
The increasing use of ventricular assist devices (VADs) in terminal heart failure patients provides new challenges to cardiac rehabilitation physicians. Structured cardiac rehabilitation strategies are still poorly implemented for this special patient group. Clear guidance and more evidence for optimal modalities are needed. Thereby, attention has to be paid to specific aspects, such as psychological and social support and education (e.g., device management, INR self-management, drive-line care, and medication).In Germany, the post-implant treatment and rehabilitation of VAD Patients working group was founded in 2012. This working group has developed clear recommendations for the rehabilitation of VAD patients according to the available literature. All facets of VAD patients' rehabilitation are covered. The present paper is unique in Europe and represents a milestone to overcome the heterogeneity of VAD patient rehabilitation.
Subject(s)
Cardiology/standards , Heart Failure/rehabilitation , Heart-Assist Devices , Ventricular Function , Heart Failure/diagnosis , Heart Failure/physiopathology , Heart-Assist Devices/standards , Humans , Prosthesis Design , Recovery of Function , Rehabilitation/standards , Treatment OutcomeABSTRACT
Historically, the human frontal pole (FP) has been considered as a single architectonic area. Brodmann's area 10 is located in the frontal lobe with known contributions in the execution of various higher order cognitive processes. However, recent cytoarchitectural studies of the FP in humans have shown that this portion of cortex contains two distinct cytoarchitectonic regions. Since architectonic differences are accompanied by differential connectivity and functions, the frontal pole qualifies as a candidate region for exploratory parcellation into functionally discrete sub-regions. We investigated whether this functional heterogeneity is reflected in distinct segregations within cytoarchitectonically defined FP-areas using meta-analytic co-activation based parcellation (CBP). The CBP method examined the co-activation patterns of all voxels within the FP as reported in functional neuroimaging studies archived in the BrainMap database. Voxels within the FP were subsequently clustered into sub-regions based on the similarity of their respective meta-analytically derived co-activation maps. Performing this CBP analysis on the FP via k-means clustering produced a distinct 3-cluster parcellation for each hemisphere corresponding to previously identified cytoarchitectural differences. Post-hoc functional characterization of clusters via BrainMap metadata revealed that lateral regions of the FP mapped to memory and emotion domains, while the dorso- and ventromedial clusters were associated broadly with emotion and social cognition processes. Furthermore, the dorsomedial regions contain an emphasis on theory of mind and affective related paradigms whereas ventromedial regions couple with reward tasks. Results from this study support previous segregations of the FP and provide meta-analytic contributions to the ongoing discussion of elucidating functional architecture within human FP.
Subject(s)
Frontal Lobe/anatomy & histology , Frontal Lobe/physiology , Algorithms , Brain/anatomy & histology , Brain/physiology , Brain Mapping/methods , Cluster Analysis , Cognition/physiology , Emotions/physiology , Humans , Magnetic Resonance Imaging/methods , Neural Pathways/anatomy & histology , Neural Pathways/physiology , Positron-Emission Tomography/methodsABSTRACT
BACKGROUND: Affective disorders are associated with an increased risk of cardiovascular disease, which, at least partly, appears to be independent of psychopharmacological treatments used to manage these disorders. Reduced heart rate variability (SDNN) and a low Omega-3 Index have been shown to be associated with increased risk for death after myocardial infarction. Therefore, we set out to investigate heart rate variability and the Omega-3 Index in euthymic patients with bipolar disorders. METHODS: We assessed heart rate variability (SDNN) and the Omega-3 Index in 90 euthymic, mostly medicated patients with bipolar disorders (Bipolar-I, Bipolar-II) on stable psychotropic medication, free of significant medical comorbidity and in 62 healthy controls. Heart rate variability was measured from electrocardiography under a standardized 30 minutes resting state condition. Age, sex, BMI, smoking, alcohol consumption and caffeine consumption as potential confounders were also assessed. RESULTS: Heart rate variability (SDNN) was significantly lower in patients with bipolar disorders compared to healthy controls (35.4 msec versus 60.7 msec; P<0.0001), whereas the Omega-3 Index did not differ significantly between the groups (5.2% versus 5.3%). In a linear regression model, only group membership (patients with bipolar disorders versus healthy controls) and age significantly predicted heart rate variability (SDNN). CONCLUSION: Heart rate variability (SDNN) may provide a useful tool to study the impact of interventions aimed at reducing the increased risk of cardiovascular disease in euthymic patients with bipolar disorders. The difference in SDNN between cases and controls cannot be explained by a difference in the Omega-3 Index.
Subject(s)
Bipolar Disorder/physiopathology , Fatty Acids, Omega-3/blood , Heart Rate/physiology , Adult , Aged , Bipolar Disorder/blood , Electrocardiography , Female , Humans , Male , Middle AgedABSTRACT
BACKGROUND: Aim was to examine depressive symptoms in acutely ill schizophrenia patients on a single symptom basis and to evaluate their relationship with positive, negative and general psychopathological symptoms. METHODS: Two hundred and seventy-eight patients suffering from a schizophrenia spectrum disorder were analysed within a naturalistic study by the German Research Network on Schizophrenia. Using the Calgary Depression Scale for Schizophrenia (CDSS) depressive symptoms were examined and the Positive and Negative Syndrome Scale (PANSS) was applied to assess positive, negative and general symptoms. Correlation and factor analyses were calculated to detect the underlying structure and relationship of the patient's symptoms. RESULTS: The most prevalent depressive symptoms identified were depressed mood (80%), observed depression (62%) and hopelessness (54%). Thirty-nine percent of the patients suffered from depressive symptoms when applying the recommended cut-off of a CDSS total score of >6 points at admission. Negligible correlations were found between depressive and positive symptoms as well as most PANSS negative and global symptoms despite items on depression, guilt and social withdrawal. The factor analysis revealed that the factor loading with the PANSS negative items accounted for most of the data variance followed by a factor with positive symptoms and three depression-associated factors. LIMITATIONS: The naturalistic study design does not allow a sufficient control of study results for the effect of different pharmacological treatments possibly influencing the appearance of depressive symptoms. CONCLUSION: Results suggest that depressive symptoms measured with the CDSS are a discrete symptom domain with only partial overlap with positive or negative symptoms.
Subject(s)
Depression/diagnosis , Guilt , Schizophrenia/diagnosis , Schizophrenic Psychology , Acute Disease , Adult , Affect , Factor Analysis, Statistical , Female , Germany , Hospitalization , Humans , Male , Middle Aged , Prevalence , Psychiatric Status Rating Scales , Research Design , Severity of Illness IndexABSTRACT
OBJECTIVE: Obsessive-compulsive symptoms (OCS) constitute a major comorbidity in schizophrenia. Prevalence estimations of OCS for patients with at-risk mental states (ARMS) for psychosis vary largely. It is unclear how ARMS patients with or without comorbid OCS differ regarding general psychosocial functioning, psychotic and affective symptoms and neurocognitive abilities. METHOD: At-risk mental states patients (n = 233) from the interventional trial PREVENT (Secondary Prevention of Schizophrenia) were stratified according to the presence or absence of comorbid OCS and compared on several clinical variables. RESULTS: Patients, who fulfilled the criteria for obsessive-compulsive disorder (OCD) or presented with subclinical OCS (ARMSposOCS sample), did not significantly differ from patients without OCS (ARMSnegOCS) with regard to gender, age, premorbid verbal intelligence and levels of education. Furthermore, similar severity of depressive syndromes, basic cognitive, attenuated psychotic and brief limited intermittent psychotic symptoms were found. However, ARMSposOCS patients showed more impairment of psychosocial functioning and higher general psychopathology. In contrast, they scored higher in cognitive tasks measuring working memory and immediate verbal memory. CONCLUSION: Findings extend upon previous results due to the multidimensional assessment. Subsequent longitudinal studies might elucidate how comorbid OCS influence differential treatment response, especially to cognitive behavioural interventions and the transition rates to psychosis.
Subject(s)
Obsessive-Compulsive Disorder/diagnosis , Psychotic Disorders/diagnosis , Schizophrenia/diagnosis , Adult , Comorbidity , Female , Humans , Male , Memory, Short-Term/physiology , Mental Recall/physiology , Obsessive-Compulsive Disorder/epidemiology , Obsessive-Compulsive Disorder/physiopathology , Prodromal Symptoms , Psychotic Disorders/epidemiology , Psychotic Disorders/physiopathology , Risk , Schizophrenia/epidemiology , Schizophrenia/physiopathology , Severity of Illness Index , Young AdultABSTRACT
AIDS clinical trials (ACTs) are critical to the development of new treatments for HIV infection. However, people of color living with HIV/AIDS are involved in ACTs at disproportionally low rates, with African-Americans experiencing the greatest under-representation. In this article, we describe the core elements and key characteristics of a highly efficacious multi-component peer-driven intervention (PDI) designed to increase rates of screening for and enrollment into ACTs among African-American and Latino/Hispanic individuals, by addressing the main complex, multi-level barriers they experience to ACTs. We discuss the process of developing the intervention, the theoretical models guiding its delivery format and content, and provide an overview of the intervention's components. We then use brief case studies to illustrate a number of key issues that may arise during intervention implementation. Finally, we describe lessons learned and provide recommendations for the PDI's uptake in clinical and clinical trials settings.
Subject(s)
Acquired Immunodeficiency Syndrome/drug therapy , Black or African American/psychology , Clinical Trials as Topic/psychology , Health Knowledge, Attitudes, Practice/ethnology , Hispanic or Latino/psychology , Patient Selection , Acquired Immunodeficiency Syndrome/diagnosis , Acquired Immunodeficiency Syndrome/ethnology , Black or African American/education , Black or African American/statistics & numerical data , Attitude of Health Personnel , Clinical Trials as Topic/standards , Clinical Trials as Topic/statistics & numerical data , Fear/psychology , Female , Hispanic or Latino/education , Hispanic or Latino/statistics & numerical data , Humans , Male , Mass Screening/psychology , Patient Education as Topic/methods , Patient Navigation/methods , Patient Navigation/organization & administration , Peer Group , Selection Bias , Trust/psychologyABSTRACT
BACKGROUND: Most older adults wish to stay in their own homes even after the onset of care dependency, which is enabled by different care arrangements. General life satisfaction can serve as a criterion for assessing the functionality of these arrangements. METHODS: The study is based on a standardized survey (face-to-face interviews; n=712) performed in 2009/2010. The population consisted of persons aged ≥70 years, with a need for care, living in one of three selected Swiss German-speaking cantons. The dataset is a representative sample of the population. RESULTS: The following results were found with regard to the surveyed target group of persons aged ≥70 years, living at home and receiving formal and/or informal care: the need for care of persons ≥80 is not greater than that of persons aged 70-79 years and is not decisive for general life satisfaction. Strength of social network, presence (or absence) of pain, and satisfaction with care are more important. The odds of being satisfied with life are greater with increasing age. The social network of persons ≥80 is weaker than that of persons aged 70-79 years but contributes nonetheless to satisfaction with life.
Subject(s)
Custodial Care/statistics & numerical data , Home Care Services/statistics & numerical data , Patient Satisfaction/statistics & numerical data , Quality of Life , Age Distribution , Aged , Aged, 80 and over , Female , Germany , Humans , Male , Sex Distribution , Surveys and Questionnaires , Switzerland/epidemiologyABSTRACT
OBJECTIVE: To evaluate the predictive validity of early response in first-episode schizophrenia within a 1-year follow-up trial and to compare the resulting cutoff to the currently proposed early response definition (20% improvement by week 2). METHOD: Receiver operator characteristic (ROC) analyses were used to identify the predictive validity of the psychopathological improvement of treatment from week 1 to week 8, regarding the maintenance of response until week 52 as well as to define the most reasonable cutoff in 132 first-episode patients. The Youden Index (maximum of sensitivity and specificity) was used to compare the newly developed and the commonly used early response definition. RESULTS: Starting with week 6, a reasonable validity to predict the maintenance of response was found (area under the curve = 0.721) with the best fitting cutoff being a 51.6% PANSS total score improvement. Using this cutoff 74 patients (56%) were correctly identified to become responder and maintain response during follow-up (sensitivity: 0.747). The Youden Index was higher applying the newly developed early response cutoff featuring higher specificity compared to the commonly used early response definition. CONCLUSION: Regarding long-term treatment, it seems more appropriate to base predictions of the patient's maintenance of response not before 6 weeks of treatment.
Subject(s)
Antipsychotic Agents/therapeutic use , Haloperidol/therapeutic use , Risperidone/therapeutic use , Schizophrenia/drug therapy , Adult , Disease Progression , Double-Blind Method , Female , Humans , Longitudinal Studies , Male , ROC Curve , Schizophrenia/diagnosis , Time Factors , Treatment Outcome , Young AdultABSTRACT
Akathisia as well as younger age, early illness onset and discharge are important risk factors for suicidality in patients with first-episode schizophrenia. The aim of the present study was to analyze on a single case basis the relationship between a sudden increase in suicidality, anxiety symptoms, medication dosing and clinician- and patient-rated akathisia. A small subsample of patients demonstrated a positive relationship between suicidality and akathisia scores within the titration period of the study medication.
Subject(s)
Akathisia, Drug-Induced/psychology , Haloperidol/adverse effects , Risperidone/adverse effects , Schizophrenia/drug therapy , Schizophrenic Psychology , Suicidal Ideation , Adolescent , Adult , Age Factors , Antipsychotic Agents/adverse effects , Antipsychotic Agents/therapeutic use , Anxiety/chemically induced , Female , Haloperidol/therapeutic use , Humans , Male , Middle Aged , Psychiatric Status Rating Scales/statistics & numerical data , Risk Factors , Risperidone/therapeutic useABSTRACT
BACKGROUND: To analyse insight of illness during the course of inpatient treatment, and to identify influencing factors and predictors of insight. METHODS: Insight into illness was examined in 399 patients using the item G12 of the Positive and Negative Syndrome Scale ("lack of insight and judgement"). Ratings of the PANSS, HAMD, UKU, GAF, SOFAS, SWN-K and Kemp's compliance scale were performed and examined regarding their potential association with insight. The item G12 was kept as an ordinal variable to compare insight between subgroups of patients. RESULTS: Almost 70% of patients had deficits in their insight into illness at admission. A significant improvement of impairments of insight during the treatment (p<0.0001) was observed. At admission more severe positive and negative symptoms, worse functioning and worse adherence were significantly associated with poorer insight. Less depressive symptoms (p=0.0004), less suicidality (p=0.0218), suffering from multiple illness-episodes (p<0.0001) and worse adherence (p=0.0012) at admission were identified to be significant predictors of poor insight at discharge. CONCLUSION: The revealed predictors might function as treatment targets in order to improve insight and with it outcome of schizophrenia.
Subject(s)
Awareness/physiology , Schizophrenia/physiopathology , Acute Disease , Adult , Female , Humans , Male , Predictive Value of Tests , Psychiatric Status Rating Scales , Schizophrenia/diagnosis , Schizophrenia/therapy , Schizophrenic PsychologyABSTRACT
BACKGROUND: Self-ratings of psychotic experiences might be biased by depressive symptoms. METHOD: Data from a large naturalistic multicentre trial on depressed inpatients (n=488) who were assessed on a biweekly basis until discharge were analyzed. Self-rated psychotic symptoms as assessed with the 90-Item Symptom Checklist (SCL-90) were correlated with the SCL-90 total score, the SCL-90 depression score, the Beck Depression Inventory (BDI), the Hamilton Depression Rating Scale 21 item (HAMD-21) total score, the Montgomery Åsberg Depression Rating Scale (MADRS) total score and the clinician-rated paranoid-hallucinatory score of the Association for Methodology and Documentation in Psychiatry (AMDP) scale. RESULTS: At discharge the SCL-90 psychosis score correlated highest with the SCL-90 depression score (0.78, P<0.001) and with the BDI total score (0.64, P<0.001). Moderate correlations were found for the MADRS (0.34, P<0.001), HAMD (0.37, P<0.001) and AMDP depression score (0.33, P<0.001). Only a weak correlation was found between the SCL-90 psychosis score and the AMDP paranoid-hallucinatory syndrome score (0.15, P<0.001). Linear regression showed that change in self-rated psychotic symptoms over the treatment course was best explained by a change in the SCL-90 depression score (P<0.001). The change in clinician-rated AMDP paranoid-hallucinatory score had lesser influence (P=0.02). CONCLUSIONS: In depressed patients self-rated psychotic symptoms correlate poorly with clinician-rated psychotic symptoms. Caution is warranted when interpreting results from epidemiological surveys using self-rated psychotic symptom questionnaires as indicators of psychotic symptoms. Depressive symptoms which are highly prevalent in the general population might influence such self-ratings.
Subject(s)
Depression/complications , Depressive Disorder/complications , Inpatients/psychology , Psychotic Disorders/diagnosis , Adult , Checklist , Depression/psychology , Depressive Disorder/psychology , Diagnostic Self Evaluation , Female , Humans , Male , Middle Aged , Psychiatric Status Rating Scales , Psychometrics , Psychotic Disorders/complications , Psychotic Disorders/psychologyABSTRACT
AIMS/HYPOTHESIS: In adult human islets, insulin and glucagon production is largely restricted to individual cell populations. The production of these hormones is less segregated during development and during the differentiation of human pluripotent stem cells towards pancreatic lineages. We therefore sought to characterise the transcription factor profile of these cells that co-produce insulin and glucagon in the developing human pancreas, and thus to gain insight into their potential fate during normal pancreas development. METHODS: An immunohistochemical analysis was performed on human pancreas sections from fetal donors aged 9 to 21 weeks and from adult donors between the ages of 17 and 55 years. RESULTS: Endocrine cells were observed within the pancreas at all ages examined, with cells co-producing insulin and glucagon observed as early as 9 weeks of fetal age. The population of cells that co-produce insulin and glucagon generally decreased in prevalence with age, with negligible numbers in adult pancreas. From 9 to 16 weeks, the population of glucagon-only cells increased, while the insulin-only cells decreased in abundance. Cells that co-produced insulin and glucagon also produced the alpha cell transcription factor, aristaless related homeobox (ARX), and lacked the beta cell transcription factors pancreatic and duodenal homeobox 1 (PDX1), NK6 homeobox 1 (NKX6.1) and v-maf musculoaponeurotic fibrosarcoma oncogene homologue A (MAFA). CONCLUSIONS/INTERPRETATION: Our results indicate that cells co-producing insulin and glucagon in the developing human pancreas share a transcription factor profile that is similar to that of mature alpha cells and suggest that some maturing alpha cells briefly exhibit ectopic insulin expression. Thus cells that co-produce insulin and glucagon may represent a transient cell population, which gives rise to mature alpha cells.
Subject(s)
Glucagon/metabolism , Immunohistochemistry/methods , Insulin/metabolism , Pancreas/metabolism , Adolescent , Adult , Animals , Apoptosis , Cell Proliferation , Humans , Image Processing, Computer-Assisted , Mice , Microscopy, Fluorescence/methods , Middle Aged , Pluripotent Stem Cells/cytology , Time FactorsABSTRACT
Type-I diabetes is a chronic disease mediated by autoimmune destruction of insulin-producing ß-cells. Although progress has been made towards improving diabetes-associated pathologies and the quality of life for those living with diabetes, no therapy has been effective at eliminating disease manifestations or reversing disease progression. Here, we examined whether double-stranded adeno-associated virus serotype 8 (dsAAV8)-mediated gene delivery to endogenous ß-cells of interleukin (IL)-4 in combination with ß-cell growth factors can reverse early-onset diabetes in NOD mice. Our results demonstrate that a single treatment with dsAAV8 vectors expressing IL-4 in combination with glucagon-like peptide-1 or hepatocyte growth factor/NK1 under the regulation of the insulin promoter enhanced ß-cell proliferation and survival in vivo, significantly delaying diabetes progression in NOD mice, and reversing disease in â¼10% of treated NOD mice. These results demonstrate the ability to reverse hyperglycemia in NOD mice with established diabetes by in vivo gene transfer to ß-cells of immunomodulatory factors and ß-cell growth factors.
Subject(s)
Dependovirus/genetics , Diabetes Mellitus, Experimental/therapy , Diabetes Mellitus, Type 1/therapy , Genetic Therapy , Glucagon-Like Peptide 1/genetics , Hepatocyte Growth Factor/genetics , Insulin-Secreting Cells/metabolism , Interleukin-4/genetics , Animals , Diabetes Mellitus, Type 1/genetics , Female , Gene Transfer Techniques , Genetic Vectors , Glucagon-Like Peptide 1/metabolism , Hepatocyte Growth Factor/metabolism , Interleukin-4/metabolism , Mice , Mice, Inbred NODABSTRACT
Methane release from seafloor sediments is moderated, in part, by the anaerobic oxidation of methane (AOM) performed by consortia of archaea and bacteria. These consortia occur as isolated cells and aggregates within the sulfate-methane transition (SMT) of diffusion and seep-dominant environments. Here we report on a new SMT setting where the AOM consortium occurs as macroscopic pink to orange biofilms within subseafloor fractures. Biofilm samples recovered from the Indian and northeast Pacific Oceans had a cellular abundance of 10(7) to 10(8) cells cm(-3). This cell density is 2 to 3 orders of magnitude greater than that in the surrounding sediments. Sequencing of bacterial 16S rRNA genes indicated that the bacterial component is dominated by Deltaproteobacteria, candidate division WS3, and Chloroflexi, representing 46%, 15%, and 10% of clones, respectively. In addition, major archaeal taxa found in the biofilm were related to the ANME-1 clade, Thermoplasmatales, and Desulfurococcales, representing 73%, 11%, and 10% of archaeal clones, respectively. The sequences of all major taxa were similar to sequences previously reported from cold seep environments. PhyloChip microarray analysis detected all bacterial phyla identified by the clone library plus an additional 44 phyla. However, sequencing detected more archaea than the PhyloChip within the phyla of Methanosarcinales and Desulfurococcales. The stable carbon isotope composition of the biofilm from the SMT (-35 to -43) suggests that the production of the biofilm is associated with AOM. These biofilms are a novel, but apparently widespread, aggregation of cells represented by the ANME-1 clade that occur in methane-rich marine sediments.
Subject(s)
Archaea/metabolism , Bacteria/metabolism , Biofilms/growth & development , Geologic Sediments/microbiology , Methane/metabolism , Microbial Consortia/physiology , Anaerobiosis , Archaea/classification , Archaea/isolation & purification , Bacteria/classification , Bacteria/isolation & purification , Cluster Analysis , DNA, Archaeal/chemistry , DNA, Archaeal/genetics , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , DNA, Ribosomal/chemistry , DNA, Ribosomal/genetics , Genes, rRNA , Molecular Sequence Data , Oxidation-Reduction , Pacific Ocean , Phylogeny , RNA, Archaeal/genetics , RNA, Bacterial/genetics , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Sequence Homology, Nucleic Acid , Sulfates/metabolismABSTRACT
AIM OF THE STUDY: To assess the value of the coronary flow reserve (CFR) in the left anterior descending artery (LAD) during dobutamine stress echocardiography in the diagnosis of significant LAD stenosis (more than 70%). METHOD: Retrospective study of 81 patients with a positive stress echocardiography who underwent a coronarography. RESULTS: Measurement of coronary flow reserve was able in half echocardiographic exams. Medium Pic diastolic velocity was 0.33 m/s (SD 0.20), medium maximal diastolic velocity during stress was 0.62 m/s (SD 0.20), medium CFR was 2.25 (SD 0.65). In 50 patients LAD was not seen; in five of them LAD was occluded. The predictive positive value (PPV) of a low coronary flow reserve to detect LAD stenosis is 66.7% and the negative predictive value (NPV) is 65.4%. An abnormal anterior contraction during stress echo with a low reserve has a PPV of 75% for the diagnosis of significant IVA stenosis and a normal contraction during stress with normal coronary flow reserve means a NPV of 65%. We did not show a significant correlation between low coronary flow and abnormal contraction during stress echocardiography (kappa 0.51). CONCLUSION: Coronary flow reserve of LAD during stress echo is feasible but does not really improve exam performance to detect significant IVA stenosis. This measurement remains to be clear in coronary patients management.