Galactosaminoglycans (GalAGs) are sulfated glycans composed of alternating
-acetylgalactosamine and uronic acid units. Uronic acid epimerization, sulfation patterns and fucosylation are modifications ...observed on these molecules. GalAGs have been extensively studied and exploited because of their multiple biomedical functions. Chondroitin sulfates (CSs), the main representative family of GalAGs, have been used in alternative therapy of joint pain/inflammation and osteoarthritis. The relatively novel fucosylated chondroitin sulfate (FCS), commonly found in sea cucumbers, has been screened in multiple systems in addition to its widely studied anticoagulant action. Biomedical properties of GalAGs are directly dependent on the sugar composition, presence or lack of fucose branches, as well as sulfation patterns. Although research interest in GalAGs has increased considerably over the three last decades, perhaps motivated by the parallel progress of glycomics, serious questions concerning the effectiveness and potential side effects of GalAGs have recently been raised. Doubts have centered particularly on the beneficial functions of CS-based therapeutic supplements and the potential harmful effects of FCS as similarly observed for oversulfated chondroitin sulfate, as a contaminant of heparin. Unexpected components were also detected in CS-based pharmaceutical preparations. This review therefore aims to offer a discussion on (1) the current and potential therapeutic applications of GalAGs, including those of unique features extracted from marine sources, and (2) the potential drawbacks of this class of molecules when applied to medicine.
An epidemiological study of leishmaniasis was performed in Amazonian areas of Ecuador since little information on the prevalent Leishmania and sand fly species responsible for the transmission is ...available. Of 33 clinical specimens from patients with cutaneous leishmaniasis (CL), causative parasites were identified in 25 samples based on cytochrome b gene analysis. As reported previously, Leishmania (Viannia) guyanensis and L. (V.) braziliensis were among the causative agents identified. In addition, L. (V.) lainsoni, for which infection is reported in Brazil, Bolivia, Peru, Suriname, and French Guiana, was identified in patients with CL from geographically separate areas in the Ecuadorian Amazon, corroborating the notion that L. (V.) lainsoni is widely distributed in South America. Sand flies were surveyed around the area where a patient with L. (V.) lainsoni was suspected to have been infected. However, natural infection of sand flies by L. (V.) lainsoni was not detected. Further extensive vector searches are necessary to define the transmission cycle of L. (V.) lainsoni in Ecuador.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Constructal Design and Simulated Annealing were applied to optimize a Double T-shaped cavity.•The cavity was optimized for several height/length ratios of solid and cavity fraction areas.•The ...combination of Exhaustive Search and SA proved the best strategy to predict the design sensibility.•The height/length ratios of stem and branches had the highest sensibility over the performance.•For small height/length ratios of the solid, the Double T-shaped cavity led to the best performance.
Present numerical work comprises the application of Constructal Design (CD) and Simulated Annealing (SA) for the geometric optimization of a Double T-shaped cavity inserted into a solid wall with internal heat generation. The main goal is to minimize the dimensionless maximum excess of temperature in the solid domain. The cavity is subjected to four constraints and five degrees of freedom (DOF). The Exhaustive Search (ES) and SA methods are employed to optimize the first three DOFs, validating the SA algorithm. From the fourth level onward, new recommendations about the design influence over the system's performance are reached, combining ES and different versions of SA. Results obtained showed the importance of investigating the influence of the DOFs over thermal performance, and corresponding design, using combined SA versions and ES. The proposed methodology reduced the computational effort in comparison with purely ES. For design investigation, the highest insertion of stem and branches led to the best performance. For square solid domains, the Double T-shaped cavity obtained an intermediate performance compared with I, T, Y, H, and ψ shapes. For small height/length solid domain ratios, the best shape found here performed several times better than the best configurations found in the literature.
Mutation of the GABRA1 gene is associated with neurodevelopmental defects and epilepsy. GABRA1 encodes for the α1 subunit of the γ-aminobutyric acid type A receptor (GABAAR), which regulates the fast ...inhibitory impulses of the nervous system. Multiple model systems have been developed to understand the function of GABRA1, but these models have produced complex and, at times, incongruent data. Thus, additional model systems are required to validate and substantiate previous results. We sought to provide initial phenotypic analysis of a novel germline mutant allele. Our analysis provides a solid foundation for the future use of this allele to characterize gabra1 functionally and pharmacologically using zebrafish. We investigated the behavioral swim patterns associated with a nonsense mutation of the zebrafish gabra1 (sa43718 allele) gene. The sa43718 allele causes a decrease in gabra1 mRNA expression, which is associated with light induced hypermotility, one phenotype previously associated with seizure like behavior in zebrafish. Mutation of gabra1 was accompanied by decreased mRNA expression of gabra2, gabra3, and gabra5, indicating a reduction in the expression of additional α sub-units of the GABAAR. Although multiple sub-units were decreased, larvae continued to respond to pentylenetetrazole (PTZ), indicating that a residual GABAAR exists in the sa43718 allele. Proteomics analysis demonstrated that mutation of gabra1 is associated with abnormal expression of proteins that regulate synaptic vesicle fusion, vesicle transport, synapse development, and mitochondrial protein complexes. These data support previous studies performed in a zebrafish nonsense allele created by CRISPR/Cas9 and validate that loss of function mutations in the gabra1 gene result in seizure-like phenotypes with abnormal development of the GABA synapse. Our results add to the existing body of knowledge as to the function of GABRA1 during development and validate that zebrafish can be used to provide complete functional characterization of the gene.
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To determine the frequency and interhospital variation of bilirubin testing and identified hyperbilirubinemia in a large health maintenance organization.
Retrospective cohort study.
Eleven Northern ...California Kaiser Permanente hospitals.
A total of 51,387 infants born in 1995-1996 at >/= 36 weeks' gestation and >/= 2000 g.
Bilirubin tests and maximum bilirubin levels recorded in the first month after birth.
The proportion of infants receiving >/= 1 bilirubin test varied across hospitals from 17% to 52%. The frequency of bilirubin levels >/= 20 mg/dL (342 micromol/L) varied from .9% to 3.4% (mean: 2.0%), but was not associated with the frequency of bilirubin testing (R(2) = .02). Maximum bilirubin levels >/= 25 mg/dL (428 micromol/L) were identified in.15% of infants and levels >/= 30 mg/dL (513 micromol/L) in .01%.
Significant interhospital differences exist in bilirubin testing and frequency of identified hyperbilirubinemia. Bilirubin levels >/=20 mg/dL were commonly identified, but levels >/= 25 mg/dL were not.
The SA (Simulated Annealing) is a meta-heuristic to combinatorial and optimization problems. The main purpose here is to investigate several cooling schedules (main parameter of SA) combined with ...Constructal Design for geometric optimization of an isothermal Y-shaped cavity intruded into a solid conducting wall with internal heat generation. This shape was optimized with Exhaustive Search and Genetic Algorithm in previous studies of literature. The problem has four degrees of freedom (H/L, L1/L0, t1/t0, α) and two constraints: the cavity and auxiliary fraction cavity areas (ϕ and ψ). Five different cooling schedules are evaluated: Fast, Exponential, Boltz, BoltzExp and ConstExp1. The first three methods are default, while the others are hybrid proposed here. Firstly, it is evaluated the percentage of simulations in which the global optimal point is achieved for the case with square solid wall. Algorithms hybrid and Fast lead to the highest and lowest reliabilities to find global optimal geometries. Posteriorly, a complete optimization of the Y-shaped cavity evaluating the effect of constraints ϕ and ψ over four times optimized Y-shaped cavity are performed. Results are compared with those previously obtained with GA (Genetic Algorithm). The combination of the best cooling schedules improves even more the achievement of the global optimal shapes.
•Constructal Design and Simulated Annealing were used to optimize Y-shaped cavities.•Different cooling schedules were evaluated for prediction of optimal shapes.•Simulated Annealing predictions were compared with Exhaustive Search and Genetic Algorithm.•Hybrid cooling schedules improved the probability to achieve optimal geometries.•Combination of different cooling schedules led to the best thermal performance.
In the present work, it was phenotyped 29
Coffea canephora
clones for resistance to
Hemileia vastatrix
races II and XXXIII and investigated the presence of molecular markers associated with Coffee ...Leaf Rust (CLR) and Coffee Berry Disease (CBD) resistance loci in 67 clones. Phenotyping for resistance was performed by evaluating six components of quantitative resistance using the leaf disc technique. The averages of the components were submitted to the Scott-Knott test and to the multivariate analysis to obtain the generalized Mahalanobis distance, which was used to group the clones by the unweighted pair-group method using arithmetic averages. In screening resistance to CLR, molecular markers were evaluated associated with two resistance loci. Three sequence characterized amplified regions (SCAR) and a simple sequence repeats (SSR) markers associated with the locus of S
H
3 gene (Locus A); a SCAR and a cleaved amplified polymorphic site (CAPS) associated with a locus of resistance to races I, II and pathotype 001 of
H. vastatrix
(Locus B). For screening resistance to CBD, two SSRs were associated with the locus of the resistance Ck-1 gene (Locus C) were evaluated. The phenotyped clones were grouped into five resistance classes for each
H. vastatrix
race. Fifteen clones have locus of resistance to races I, II, and the pathotype 001 of
H. vastatrix
. Three clones have the Ck-1 gene. These results support growers to choose resistant clones for crop composition and indicate potential sources of CLR and CBD resistance for
C. canephora
breeding programs.
ABSTRACT
BACKGROUND
Patients admitted to general medicine inpatient services are increasingly cared for by hospital-based physicians rather than their primary care providers (PCPs). This separation ...of hospital and ambulatory care may result in important care discontinuities after discharge. We sought to determine whether communication between hospital-based physicians and PCPs influences patient outcomes.
METHODS
We approached consecutive patients admitted to general medicine services at six US academic centers from July 2001 to June 2003. A random sample of the PCPs for consented patients was contacted 2 weeks after patient discharge and surveyed about communication with the hospital medical team. Responses were linked with the 30-day composite patient outcomes of mortality, hospital readmission, and emergency department (ED) visits obtained through follow-up telephone survey and National Death Index search. We used hierarchical multi-variable logistic regression to model whether communication with the patient’s PCP was associated with the 30-day composite outcome.
RESULTS
A total of 1,772 PCPs for 2,336 patients were surveyed with 908 PCPs responses and complete patient follow-up available for 1,078 patients. The PCPs for 834 patients (77%) were aware that their patient had been admitted to the hospital. Of these, direct communication between PCPs and inpatient physicians took place for 194 patients (23%), and a discharge summary was available within 2 weeks of discharge for 347 patients (42%). Within 30 days of discharge, 233 (22%) patients died, were readmitted to the hospital, or visited an ED. In adjusted analyses, no relationship was seen between the composite outcome and direct physician communication (adjusted odds ratio 0.87, 95% confidence interval 0.56 – 1.34), the presence of a discharge summary (0.84, 95% CI 0.57–1.22), or PCP awareness of the index hospitalization (1.08, 95% CI 0.73–1.59).
CONCLUSION
Analysis of communication between PCPs and inpatient medical teams revealed much room for improvement. Although communication during handoffs of care is important, we were not able to find a relationship between several aspects of communication and associated adverse clinical outcomes in this multi-center patient sample.
To evaluate the acceptability, practicality, and short-term efficacy of a health education program to improve disease self-management in patients with symptomatic HIV/AIDS.
Randomized controlled ...trial, baseline and 3-month follow-up questionnaire assessments.
San Francisco Bay communities.
Seventy-one men with symptomatic HIV or AIDS were randomly assigned to a seven-session group educational intervention (N=34) or a usual-care control group (N=37).
Interactive health education groups were used to teach wide-ranging disease self-management skills and information: symptom assessment and management, medication use, physical exercise, relaxation, doctor-patient communication, and nutrition. Each group was led by two trained peer-leaders (one of whom was HIV-positive) recruited from the community.
The primary outcome of interest was symptom status. Secondary outcomes were self-efficacy and health behaviors. Analysis of covariance was used to compare experimental and control group mean outcomes, adjusting for baseline value differences.
The symptom severity index (number of symptoms moderate or greater severity) decreased in the experimental, and increased in the control group (-0.9 versus +0.5; p < .03). Pain, fatigue, and psychological symptoms were not significantly different between groups. Self-efficacy for controlling symptoms improved in the experimental, and decreased in the control group (+4 versus -7; p < .02). Changes in stress/relaxation exercises and HIV/AIDS knowledge were not different between groups. A trend was shown toward more frequent physical exercise in the experimental group compared with less in the control group (+1.3 versus -0.5 times/week; p=.06).
Health education emphasizing self-management skills for HIV/AIDS patients can be implemented and evaluated and was accepted by patients, peer-leaders, and health care providers. Whether this educational program can lead to prolonged improvement in HIV symptoms and behaviors can be adequately addressed only by a larger trial of longer duration.
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