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pubmed_472_1504 | Integrins αMβ2 and αXβ2 are homologous adhesive receptors that are expressed on many of the same leukocyte populations and bind many of the same ligands. Although αMβ2 was extensively characterized and implicated in leukocyte inflammatory and immune functions, the roles of αXβ2 remain largely obscure. Here, we tested the ability of mice deficient in integrin αMβ2 or αXβ2 to deal with opportunistic infections and the capacity of cells derived from these animals to execute inflammatory functions. The absence of αMβ2 affected the recruitment of polymorphonuclear neutrophils (PMN) to bacterial and fungal pathogens as well as to model inflammatory stimuli, and αMβ2-deficient PMN displayed defective inflammatory functions. In contrast, deficiency of αXβ2 abrogated intraperitoneal recruitment and adhesive functions of monocytes and macrophages (Mϕ) and the ability of these cells to kill/phagocytose Candida albicans or Escherichia coli cells both ex vivo and in vivo During systemic candidiasis, the absence of αXβ2 resulted in the loss of antifungal activity by tissue Mϕ and inhibited the production of tumor necrosis factor alpha (TNF-α)/interleukin-6 (IL-6) in infected kidneys. Deficiency of αMβ2 suppressed Mϕ egress from the peritoneal cavity, decreased the production of anti-inflammatory IL-10, and stimulated the secretion of IL-6. The absence of αXβ2, but not of αMβ2, increased survival against a septic challenge with lipopolysaccharide (LPS) by 2-fold. Together, these results suggest that αMβ2 plays a primary role in PMN inflammatory functions and regulates the anti-inflammatory functions of Mϕ, whereas αXβ2 is central in the regulation of inflammatory functions of recruited and tissue-resident Mϕ. | 10.1128/IAI.00644-16 |
pubmed_682_8285 | The growing awareness of Fontan-associated liver disease (FALD) in adults with Fontan physiology has provided the impetus to better understand the natural history of FALD and develop a reliable noninvasive method to diagnose and monitor liver health in this population. Biochemical and imaging tests have been investigated to determine their association with liver pathology. The congestive hepatopathy that develops after the Fontan procedure has made interpreting these tests challenging. We have reviewed and summarized the current understanding and ongoing challenges with respect noninvasive measures of liver health in Fontan patients including biochemical tests, elastography, hepatic ultrasound, cross-sectional imaging, and hemodynamics and how they relate to liver pathology. It has been demonstrated from biopsy data that liver disease is universal and progressive in Fontan patients. Traditional biochemical tests, elastography, and imaging methods are often abnormal in Fontan patients but do not reliably indicate significant liver pathology. Although a reliable means for surveillance of FALD remains elusive, this continues to be an active area of investigation, with promising recent developments. Therapeutic options for FALD are limited, with cardiac transplant as the only option that can stabilize FALD pathology and improve symptomatology. Given the limited therapeutic options and the prevalence of liver disease in Fontan patients, there is a compelling case for early routine surveillance of liver health and promotion of global liver health. | 10.1016/j.cjca.2018.11.019 |
pubmed_890_18715 | Different conventional and causal approaches have been proposed for mediation analysis to better understand the mechanism of a treatment. Count and zero-inflated count data occur in biomedicine, economics, and social sciences. This paper considers mediation analysis for count and zero-inflated count data under the potential outcome framework with nonlinear models. When there are post-treatment confounders which are independent of, or affected by, the treatment, we first define the direct, indirect, and total effects of our interest and then discuss various conditions under which the effects of interest can be identified. Proofs are provided for the sensitivity analysis proposed in the paper. Simulation studies show that the methods work well. We apply the methods to the Detroit Dental Health Project's Motivational Interviewing DVD trial for the direct and indirect effects of motivational interviewing on count and zero-inflated count dental caries outcomes. | 10.1177/0962280216686131 |
pubmed_290_7415 | Sarcomere length (SL) instability and SL non-uniformity have been used to explain fundamental properties of skeletal muscles, such as creep, force depression following active muscle shortening and residual force enhancement following active stretching of muscles. Regarding residual force enhancement, it has been argued that active muscle stretching causes SL instability, thereby increasing SL non-uniformity. However, we recently showed that SL non-uniformity is not increased by active muscle stretching, but it remains unclear if SL stability is affected by active stretching. Here, we used single myofibrils of rabbit psoas muscle and measured SL non-uniformity and SL instability during isometric contractions and for isometric contractions following active stretching at average SLs corresponding to the descending limb of the force-length relationship. We defined isometric contractions as contractions during which mean SL remained constant. SL instability was quantified by the rate of change of individual SLs over the course of steady-state isometric force and SL non-uniformity was defined as deviations of SLs from the mean SL at an instant of time. We found that whereas the mean SL remained constant during isometric contraction, by definition, individual SLs did not. SLs were more stable in the force-enhanced, isometric state following active stretching compared with the isometric reference state. We also found that SL instability was not correlated with the rate of change of SL non-uniformity. Also, SL non-uniformity was not different in the isometric and the post-stretch isometric contractions. We conclude that since SL is more stable but similarly non-uniform in the force-enhanced compared with the corresponding isometric reference contraction, it appears unlikely that either SL instability or SL non-uniformity contribute to the residual force enhancement property of skeletal muscle. | 10.1242/jeb.209924 |
pubmed_359_20205 | OBJECTIVE
This study aimed to evaluate the association of diarrhea and acute lower respiratory tract infections (ALRI) with growth of preschool children.
DESIGN
A longitudinal community-based study over a 12-month period. Children were followed up with thrice-weekly household visits for collection of morbidity data. Every 4 months (round) clinical and anthropometric examinations were performed. At baseline a questionnaire was used to collect socioeconomic family data and environmental household variables. Generalized estimating equation was used in the statistical analysis. The variations in weight-for-age or height-for-age Z-scores in each round were the dependent variables, while the main independent variables were the number of days with diarrhea and ALRI.
SETTING
Serrinha, located in Northeast Brazil.
SUBJECTS
In total, 487 children, aged 6-48 months at baseline, with 1-y complete follow-up.
RESULTS
The number of sick days with diarrhea or ALRI was not associated with mean changes in weight-for-age Z-scores. However, the mean of height-for-age Z-scores was found to decrease in those children with 7 or more days of diarrhea (beta=-0.0472; P=0.016) but not with 1 or more days of ALRI (beta=0.0022; P=0.406) in all rounds of the follow-up period.
CONCLUSION
Results of the study reinforce the concept of diarrhea burden as a major determinant of poor growth in children under 5 y of age. Actions targeted to decrease the risk factors for the occurrence of diarrhea may represent an important component of interventions aimed to ensure satisfactory child growth. | 10.1038/sj.ejcn.1602245 |
pubmed_311_24159 | Little is known about fostering sustainable, collaborative community-academic partnerships that effectively improve physical activity and health in residents of under resourced communities using Participatory Action Research (PAR) driven models. The purpose of this PAR study was to evaluate the impact of an urban, intergenerational, and physical activity dance program by identifying community preferred measurable outcomes that promote program participation and sustainability. A descriptive, qualitative design was employed using semi-structured interview guides to facilitate discussions for two adult focus groups and one youth focus group. Exactly 19 community-residing adults and six youth who lived in urban neighborhoods in West Philadelphia participated in the discussions. The audiotapes were transcribed and analyzed using directed content analysis. Five outcome themes emerged and included: (1). Enhancing the psychological and emotional well-being of the individual, (2). Enhancement of social well-being and management of interpersonal relationships and responsibilities (3). Enhancing and promoting physiologic well-being (4). Changes in health promoting behaviors and skill acquisition, and (5). Concerns about accessibility of dance for health and other physical activity programs in the community. Focused attention to measuring community preferred outcomes can promote sustainability of Dance for Health and possibly other urban-based physical activity dance programs. | 10.3390/bs8120113 |
pubmed_1094_21753 | The present study aimed to examine the associations between the protein and mRNA expression levels of ovarian cancer gene 1 (OVCA1), cyclin D1 and p16 and high-risk human papillomavirus (HR-HPV) infection in cervical lesions. The protein expression levels of OVCA1, cyclin D1 and p16 in 66 cases of cervical cancer, 64 cases of cervical intraepithelial neoplasia (CIN) and 34 normal cervix tissues were detected using immunohistochemistry. The mRNA expression levels of OVCA1, cyclin D1 and p16 in cervical cancer and normal cervix cells were detected using real-time polymerase chain reaction. The results revealed that the protein expression levels of OVCA1 increased gradually, whereas its mRNA expression levels decreased gradually, in the progression from normal cervix tissue to CIN and cervical cancer (P<0.01). In addition, significant differences in the protein expression levels of OVCA1 between low-and high-level CIN, as well as between the early and advanced stages of cervical cancer, were observed (P<0.05). No significant associations were detected between the protein and mRNA expression levels of OVCA1 and the pathological type of cervical cancer or the presence of lymph node metastasis (P>0.05). The expression levels of OVCA1 mRNA and protein were positively correlated with the levels of p16 expression (P<0.01). Significant differences were also observed in the OVCA1 protein and mRNA expression levels between the HR-HPV (+) and HR-HPV (-) groups (P<0.05). Therefore, aberrant expression of OVCA1 protein and mRNA may be important during the development of cervical lesions, particularly in the early stages. In addition, the mechanisms underlying the effects of OVCA1 during cervical cancer development may involve p16 and HPV, as the levels of OVCA1 in cervical lesions were correlated with abnormal expression of p16 and HR-HPV infection. | 10.3892/ol.2017.5848 |
pubmed_478_612 | BACKGROUND
Brazil is currently debating the implementation of front-of-package labels. This study tested if Warning labels (WLs) improved consumer understanding, perceptions, and purchase intentions compared to Traffic-Light labels (TLLs) in 1607 Brazilian adults.
METHODS
In this online, randomized controlled experiment participants saw images of 10 products and answered questions twice-once in a no-label, control condition and then again in a randomly assigned label condition. The relative differences in responses between WLs and TLLs between control and label conditions were estimated using one-way ANOVAs or Chi-square tests.
RESULTS
Presenting WLs on products compared to TLLs helped participants: (i) improve their understanding of excess nutrient content (27.0% versus 8.2%, p < 0.001); (ii) improve their ability to identify the healthier product (24.6% versus 3.3%, p < 0.001); (iii) decrease perceptions of product healthfulness; and (iv) correctly identify healthier products (14.0% versus 6.9%, p < 0.001), relative to the control condition. With WLs, there was also an increase in the percentage of people: (v) expressing an intention to purchase the relatively healthier option (16.1% versus 9.8%, p < 0.001); and (vi) choosing not to buy either product (13.0% versus 2.9%, p < 0.001), relative to the control condition. The participants in the WL condition had significantly more favorable opinions of the labels compared to those in the TLL group.
CONCLUSIONS
WLs would be more effective at improving consumer food choices. | 10.3390/nu10060688 |
pubmed_99_415 | We assessed the vascular, phosphaturic, and calcemic responses to several synthetic parathyroid hormone (PTH) analogues. Bovine (b) PTH (1-34), human (h) PTH (1-34), hPTH (53-84), [ Nle8 , Nle18 , Tyr34 ]bPTH (1-34), and [ Nle8 , Nle18 , Tyr34 ]bPTH (3-34) were administered in doses between 1 and 500 micrograms/kg as bolus intravenous injections to male Wistar-Kyoto rats aged 18-26 wk. Antagonism of the action of PTH was assessed in rats pretreated with 10 or 100 micrograms/kg [ Nle8 , Nle18 , Tyr34 ]bPTH (3-34) followed by 10 micrograms/kg of bPTH (1-34), or with 10 micrograms/kg hPTH (53-84) followed by 10 micrograms/kg hPTH (1-34). Bovine PTH (1-34), hPTH (1-34), and [ Nle8 , Nle18 , Tyr34 ]bPTH (1-34) produced virtually identical log dose-dependent hypotension, with 100 micrograms/kg of each analogue producing a 56% reduction in mean arterial pressure. Neither hPTH (53-84) nor [ Nle8 , Nle18 , Tyr34 ]bPTH (3-34) demonstrated any effect on mean arterial pressure at doses up to 500 micrograms/kg. Pretreatment with the inactive analogues failed to antagonize the vasodilating response to either bPTH (1-34) or hPTH (1-34). The vasoactive analogues significantly increased urinary phosphorus excretion while the inactive analogues did not modify it. hPTH (1-34) produced a modest decrease in serum Ca2+ at 1 min after injection. The results document that the vasodilating effect of PTH is a specific action of the peptide. Deletion of the first two amino acid residues abolishes both the phosphaturic and hypotensive effects of the peptide. Acute changes in serum Ca2+ do not appear to be a prerequisite for the vasodilatory response. Inactive analogues of PTH do not antagonize the vascular actions of the peptide. | 10.1152/ajprenal.1984.246.5.F551 |
pubmed_815_2255 | This paper addresses the relevance and implementation of health education in the Accident & Emergency (A & E) department. The functions of an A & E department and the changing role of A & E nursing are introduced and the scope for health education in A & E is critically discussed. Factors which influence effective and realistic health education, such as inequalities of health, locus of control and the environment within a busy A & E department, are briefly explored. Finally, some recommendations for the implementation of realistic, meaningful health education are offered. | 10.1016/0965-2302(94)90067-1 |
pubmed_17_13321 | NMNAT (nicotinamide 5'-mononucleotide adenylyltransferase; EC 2.7.7.1) catalyses the transfer of the adenylyl group from ATP to NMN to form NAD. We have cloned a novel human NMNAT cDNA, designated hNMNAT-2, from human brain. The cDNA contains a 924 bp open reading frame that encodes a 307 amino acid peptide that was expressed as a histidine-patch-containing thioredoxin fusion protein. Expressed hNMNAT-2 shared only 35% amino acid sequence homology with the human NMNAT enzyme (hNMNAT-1), but possessed enzymic activity comparable with hNMNAT-1. Using human genomic databases, hNMNAT-2 was localized to chromosome 1q25 within a 171 kb gene, whereas hNMNAT-1 is on chromosome 1p32-35. Northern blot analysis revealed highly restricted expression of hNMNAT-2 to brain, heart and muscle tissues, which contrasts with the wide tissue expression of hNMNAT-1; different regions of the brain exhibited differential expression of hNMNAT-2. Substitution mutations of either of two invariant residues, His-24 or Trp-92, abolished enzyme activity. Anti-peptide antibody to a unique epitope within hNMNAT-2 was produced, and immunohistochemical analysis of sections of normal adult human pancreas revealed that hNMNAT-2 protein was markedly expressed in the islets of Langerhans. However, the pancreatic exocrine cells exhibited weak expression of hNMNAT-2 protein. Sections of pancreas from insulinoma patients showed strong expression of hNMNAT-2 protein in the insulin-producing tumour cells, whereas acinar cells exhibited relatively low expression of hNMNAT-2 protein. These data suggest that the unique tissue-expression patterns of hNMNAT-2 reflect distinct functions for the isoforms in the regulation of NAD metabolism. | 10.1042/BJ20030518 |
pubmed_839_11715 | Although considerable efforts have been made in the discovery of new agents for cancer treatment, several promising therapeutics cannot be applied systemically because of their severe side effects. This is the case for various recombinant pro-inflammatory cytokines that, despite their potent anti-cancer activity, can not find their way to clinical exploitation due to their devastating toxicity shown during dose escalation to therapeutically active concentrations. To circumvent these problems, an elegant and efficient way to accumulate therapeutic agents at the tumor site, thus reducing systemic side effects, is their conjugation to tumor-specific antibodies. Here, we review preclinical data about immunocytokines conjugated to a promising single-chain human antibody that selectively targets tumor-associated stroma and blood vessels by binding with high affinity and specificity to the extra domain-B (EDB) of fibronectin. | 10.1016/j.imbio.2009.06.005 |
pubmed_15_6535 | OBJECTIVE
To establish an in vitro model of degeneration of human cervical endplate chondrocytes and observe the morphology and phenotypes of endplate chondrocytes in normal and degenerative cervical vertebral endplates.
METHODS
Cartilage endplates of 49 patients were divided into control group (n = 19) with cervical vertebral fracture or dislocation and experiment group (n = 30) with cervical spondylotic myelopathy. Endplate chondrocytes were isolated by enzyme digestion and cultured in vitro. The morphological appearances, growth curve and biological characteristics of endplate chondrocytes from normal and degenerative cartilage endplate were observed by inverted phase contrast microscope, HE staining, MTT, toluidine blue staining and reverse transcription-polymerase chain reaction (RT-PCR) respectively. RT-PCR was used to detect the mRNA expression of aggrecan, type II collagen and type I collagen.
RESULTS
The endplate chondrocytes expressed aggrecan, type II collagen and type I collagen. The phenotypes and biological characteristics were similar to those of articular chondrocytes. The morphological appearance of primary endplate chondrocytes in the control group were mostly polygons, nucleus with round or ellipse, sometimes nuclei, vacuoles in intra cytoplasm, expressing a high proliferating rate. The cells of the experiment group were fusiform and their proliferating rates decreased. Compared with the control group, the mRNA expression of aggrecan (0.695 ± 0.052 vs 0.950 ± 0.032, t = 7.263, P = 0.002) and type II collagen (0.726 ± 0.035, 0.907 ± 0.078, t = 3.681, P = 0.021) markedly decreased. And the mRNA expression of type I collagen (0.795 ± 0.028 vs 0.552 ± 0.070, t = -5.560, P = 0.005) increased in the experiment group.
CONCLUSION
A degenerative cell model of human cervical endplate chondrocytes has been established successfully in vitro. It may offer the cytological rationales for exploring the mechanism of intervertebral disc degeneration. And the previous restrictions of studying only the model of animal cells shall be resolved. | pubmed_15_6535 |
pubmed_946_5634 | General immunobiologic studies in cancer patients have stressed measurements of lymphocyte function and have commonly ignored the monocyte-macrophage system. A preliminary study of peripheral blood monocyte-macrophage function was undertaken in a group of 90 cancer patients (18 breast, 32 colon, 13 head and neck, 9 lung, and 18 melanoma) and 70 controls. Studies included enumeration of extractible monocytes (EM), quantitation of differentiation into macrophages (macrophage precursor test: MP), evaluation of antibody-dependent cellular cytotoxicity (ADCC), and spontaneous cellular cytotoxicity (SCC) as measured with human erythrocytes, and measurements of monocyte and serum lysozyme activity. Breast cancer patients had normal profiles. Colon cancer patients showed the most profound abnormalities with decreased EM and MP and increased ADCC and SCC. Patients with Stage I and Stage II melanoma had normal profiles, whereas those with advanced melanoma had significantly decreased MP. This defect was restored in two patients by BCG immunotherapy. Head and neck cancer and benign breast disease patients had decreased EM, whereas patients with lung cancer had increased EM. Monocyte lysozyme production was unchanged in the cancer patients compared to controls. Serum lysozyme levels, however, were significantly increased in patients with cancers of the colon, head and neck, and lung. Although patients with localized breast cancer and melanoma had normal levels, these were increased in both patient groups with advanced disease. It would appear that the source of the increased serum lysozyme is probably not the peripheral blood monocytes, but could have originated in the intra-tumoral or tissue-bound macrophages which were not examined. Selected assays of peripheral blood monocyte function were deranged in certain types of cancer patients but were fully normal in others, and did not show consistent correlations with tumor type or stage. Tissue-bound or intra-tumoral macrophages might provide a more fruitful area for study in these disease categories. | 10.1002/1097-0142(19830215)51:4<669::aid-cncr2820510420>3.0.co;2-1 |
pubmed_311_10514 | Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) affects systemic small vessels and is accompanied by the presence of ANCAs in the serum. This disease entity includes microscopic polyangiitis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis and drug-induced AAV. Similar to other autoimmune diseases, AAV develops in patients with a predisposing genetic background who have been exposed to causative environmental factors. The mechanism by which ANCAs cause vasculitis involves ANCA-mediated excessive activation of neutrophils that subsequently release inflammatory cytokines, reactive oxygen species and lytic enzymes. In addition, this excessive activation of neutrophils by ANCAs induces formation of neutrophil extracellular traps (NETs). Although NETs are essential elements in innate immunity, excessive NET formation is harmful to small vessels. Moreover, NETs are involved not only in ANCA-mediated vascular injury but also in the production of ANCAs themselves. Therefore, a vicious cycle of NET formation and ANCA production is considered to be involved in the pathogenesis of AAV. In addition to this role of NETs in AAV, some other important discoveries have been made in the past few years. Incorporating these new insights into our understanding of the pathogenesis of AAV is needed to fully understand and ultimately overcome this disease. | 10.1038/s41584-018-0145-y |
pubmed_895_22121 | SUMMARY Approximately 28% of the total occupational therapy (OT) faculty in higher education are adjunct faculty members. Adjunct faculty (i.e., faculty who teach a course or part of a course) have been used in higher education to maintain quality educational experiences while providing positive community connections and educational resources with first-hand experience. In occupational therapy, practitioners often assume adjunct faculty responsibilities, thereby significantly increasing professional workloads. Despite added effort, there are several benefits to adjunct teaching. However, there are equally as many challenges. Objectives of this article were to describe rewards and challenges of adjunct teaching and suggest strategies for successfully negotiating adjunct roles. The article summarizes findings from needs assessments undertaken to develop adjunct faculty programs. Results are relevant to practitioners with both clinical and teaching roles, and to their supervisors and peers. | 10.1080/J003v15n01_13 |
pubmed_312_20069 | Fused silica capillary columns (Durabond) have been evaluated for the screening of more than 100 basic drugs in postmortem blood samples. The combination of these columns, nitrogen-phosphorus detectors, and SKF-525A (internal standard) allows for the simultaneous screening and quantitation of several basic drugs such as amphetamines, amitriptyline, and codeine. Approximately 2000 blood samples have been analyzed by this procedure. The use of capillary columns results in excellent baseline stability and this, together with an autosampler and data system, enables unattended overnight operation. "Double peaking" associated with splitless injection can be a problem as can sensitivity for some of the polar drugs; however, with the extraction procedure described and the equipment used, the screening of blood for basic drugs is improved when compared with packed column technology. | pubmed_312_20069 |
pubmed_229_3594 | The tendency is to use small cannulas for operative laparoscopy; however, working with these cannulas may have technical limitations. We developed a technique for performing appendectomy combining culdoscopy and minilaparoscopy. It uses 3- or 5-mm abdominal cannulas, and the large 10- or 12-mm cannula is inserted into the posterior vaginal fornix under laparoscopic surveillance. The vaginal port is used to introduce operative instruments and extract specimens, and for vision. Culdolaparoscopy avoids additional or large abdominal ports, thus overcoming limitations of small cannulas. | 10.1016/s1074-3804(05)60346-5 |
pubmed_807_23058 | STUDY DESIGN
Three experiments to validate the use of the flexible electrogoniometer (FEG) as a tool to measure thoracic kyphosis.
OBJECTIVE
To investigate the accuracy, test-retest reliability, and concurrent validity of the FEG as applied to the thoracic spine.
SUMMARY OF BACKGROUND DATA
Thoracic kyphosis is commonly measured by the Cobb angle from lateral radiograph. Other less-invasive tools have been developed, but all yield only static measurements or are restricted to the laboratory. The FEG, which can record joint angles over time outside the laboratory, has been used to measure other joints but has not yet been validated for measurement of the thoracic spine.
METHODS
First, the FEG was bench-tested against a plurimeter for accuracy. Second, 12 subjects performed 7 functional activities 1 week apart to assess the test-retest reliability. Finally, to examine concurrent validity, 12 subjects underwent radiography in "upright" and "slumped" standing with the FEG attached to the skin over their thoracic spine. Three Cobb angles, which corresponded with the inner, mid, and outer margins, respectively, of the overlying FEG end blocks were compared with the FEG angles.
RESULTS
The correlation between the FEG and the plurimeter was excellent (r > 0.99, P < 0.0001), although some accuracy was lost at extremes of range. The mean correlation between the first and second measurements was very strong (intraclass correlation coefficient(2,1) 0.92, P < 0.0001; range, 0.89-0.95). The mid-Cobb angle showed the least absolute angular difference from, and was highly correlated with, the FEG angle (r = 0.81, P < 0.01).
CONCLUSION
The FEG demonstrated excellent accuracy and test-retest reliability and correlated very well with the Cobb angle. The FEG measurement seemed to correspond most closely with the Cobb angle measured between the middle of the FEG end blocks. | 10.1097/BRS.0b013e3181d13039 |
pubmed_629_16403 | OBJECTIVES
The current World Health Organization (WHO) definition of osteoporosis, which is based on densitometry of lumbar and femoral regions, is extensively used for decision-making in clinical practice. Discordance in diagnosis of osteoporosis using this definition is a known phenomenon. The aim of this study was to evaluate the impact of such discordance and to assess the diagnostic value of using one skeletal site for screening purposes as opposed to the two sites required in the WHO criteria.
STUDY DESIGN
Data was collected from 4188 individuals (3848 female); mean age=53.4 years (standard deviation 11.8) referred to a community-based outpatient osteoporosis testing centre in Tehran, Iran.
METHODS
Dual-energy X-ray absorptiometry (DXA) was performed on L1-L4 lumbar spine and total hip for all cases. The DXA results were categorized according to WHO criteria. Sensitivity for each site was calculated as number of cases with T-score < -2.5 at that site divided by the total number of cases with T-score < -2.5 at any site.
RESULTS
Prevalence of osteoporosis diagnosis using lumbar DXA, femoral DXA, and WHO criteria (either of the sites) were 24.7%, 12.4%, and 27.8%, respectively. Sensitivity of lumbar DXA for diagnosis of osteoporosis (88.9%) was significantly higher than femoral DXA (44.6%, P<0.001); but this difference became non-significant for men > or = 60 and women > or = 70 (P=0.615 and P=0.077, respectively). Agreement of the procedures in different sites (kappa) was 0.40 (0.37 to 0.43). When proximal femur was considered as the reference, positive likelihood ratios of lumbar DXA to detect cases were 4.7 and 2.0 in younger and older groups, respectively.
CONCLUSIONS
Concerning the high rate of discordance and low agreement between DXA results, the data obtained from each anatomical site cannot predict the condition of the other site. However, if use of a single assessment is intended for screening programs, public health authorities can develop different strategies for different age groups of their population. We propose lumbar DXA for the younger group (men < 60 and women < 70) and femoral densitometry for the older. | 10.1016/j.puhe.2006.05.013 |
pubmed_249_16410 | Natural killer cells can discriminate between normal cells and cells that do not express adequate amounts of major histocompatibility complex (MHC) class I molecules. The discovery, both in mouse and in human, of MHC-specific inhibitory receptors clarified the molecular basis of this important NK cell function. However, the triggering receptors responsible for positive NK cell stimulation remained elusive until recently. Some of these receptors have now been identified in humans, thus shedding some light on the molecular mechanisms involved in NK cell activation during the process of natural cytotoxicity. Three novel, NK-specific, triggering surface molecules (NKp46, NKp30, and NKp44) have been identified. They represent the first members of a novel emerging group of receptors collectively termed natural cytotoxicity receptors (NCR). Monoclonal antibodies (mAbs) to NCR block to differing extents the NK-mediated lysis of various tumors. Moreover, lysis of certain tumors can be virtually abrogated by the simultaneous masking of the three NCRs. There is a coordinated surface expression of the three NCRs, their surface density varying in different individuals and also in the NK cells isolated from a given individual. A direct correlation exists between the surface density of NCR and the ability of NK cells to kill various tumors. NKp46 is the only NCR involved in human NK-mediated killing of murine target cells. Accordingly, a homologue of NKp46 has been detected in mouse. Molecular cloning of NCR revealed novel members of the Ig superfamily displaying a low degree of similarity to each other and to known human molecules. NCRs are coupled to different signal transducing adaptor proteins, including CD3 zeta, Fc epsilon RI gamma, and KARAP/DAP12. Another triggering NK receptor is NKG2D. It appears to play either a complementary or a synergistic role with NCRs. Thus, the triggering of NK cells in the process of tumor cell lysis may often depend on the concerted action of NCR and NKG2D. In some instances, however, it may uniquely depend upon the activity of NCR or NKG2D only. Strict NKG2D-dependency can be appreciated using clones that, in spite of their NCR(dull) phenotype, efficiently lyse certain epithelial tumors or leukemic cell lines. Other triggering surface molecules including 2B4 and the novel NKp80 appear to function as coreceptors rather than as true receptors. Indeed, they can induce natural cytotoxicity only when co-engaged with a triggering receptor. While an altered expression or function of NCR or NKG2D is being explored as a possible cause of immunological disorders, 2B4 dysfunction has already been associated with a severe form of immunodeficiency. Indeed, in patients with the X-linked lymphoproliferative disease, the inability to control Epstein-Barr virus infections may be consequent to a major dysfunction of 2B4 that exerts inhibitory instead of activating functions. | 10.1146/annurev.immunol.19.1.197 |
pubmed_1044_190 | A bivariate conditionally specified distribution is one in which the dependence relationship between the two random variables is accomplished by defining the distribution of one of the random variables, given the other. One such conditionally specified model is called the pseudo-exponential distribution, where both the marginal distribution of one and the conditional distribution of the other, given the first, are exponential. In this paper, a variation of this conditioning regime is introduced, and its characteristics are contrasted with the original. An example is used to demonstrate the applicability of the new model. Per-capita Gross Domestic Product (GDP) is a measure of a nation's total annual production of goods and services, divided by its population. Two variations of both the original and the new conditioning regime are applied to GDP and infant mortality data across nations and territories. Possible generalizations are considered. | 10.1080/02664763.2019.1686132 |
pubmed_372_6550 | In 2014, a multidisciplinary consensus on the classification of pre- and postnatal urinary tract dilation (UTD classification) was developed. Its goal was to provide a standardized system for evaluating and reporting urinary tract dilation both in the prenatal and postnatal periods. In this review, we summarize insights learned from the implementation of the UTD classification system since its inception, providing clarifications on common points of confusion. In addition, we review current literature in the clinical validation of the UTD classification system to provide credence for its use in managing fetuses and children with urinary tract dilation. | 10.1007/s00247-021-05263-w |
pubmed_119_606 | Specific degradation of the phospholipid membrane of guinea-pig liver microsomal fraction with phospholipase A inactivated glucuronyltransferase. The inactivation was reversed by phosphatidylcholine and mixed microsomal phospholipid micelles at concentrations similar to those present in intact microsomal preparations. The other commonly occurring phospholipids did not reactivate phospholipase A-treated enzyme. Since the mixed microsomal phospholipids consisted mainly of phosphatidylcholine, it is concluded that the reactivation by phospholipids is phosphatidylcholine-specific. Reactivation was also achieved by low concentrations of the cationic detergents cetylpyridinium chloride and cetyltrimethylammonium bromide. Higher concentrations of these detergents inactivated the glucuronyltransferase activity of intact and phospholipase A-treated microsomal fractions. Anionic detergents were potent inactivators of the glucuronyltransferase activity of untreated and phospholipase A-treated microsomal fractions, whereas non-ionic detergents had little effect on the activity of either preparation. Measurements of the zeta-potentials of the micellar species used in this study showed that no obvious relationship existed between the zeta-potentials and the ability to reactivate glucuronyltransferase. However, high positive or negative zeta-potentials were correlated with the ability of the amphipathic compound to inactivate glucuronyltransferase. | 10.1042/bj1230875 |
pubmed_31_8031 | This paper explores cutting-edge deep learning methods for information extraction from medical imaging free text reports at a multi-institutional scale and compares them to the state-of-the-art domain-specific rule-based system - PEFinder and traditional machine learning methods - SVM and Adaboost. We proposed two distinct deep learning models - (i) CNN Word - Glove, and (ii) Domain phrase attention-based hierarchical recurrent neural network (DPA-HNN), for synthesizing information on pulmonary emboli (PE) from over 7370 clinical thoracic computed tomography (CT) free-text radiology reports collected from four major healthcare centers. Our proposed DPA-HNN model encodes domain-dependent phrases into an attention mechanism and represents a radiology report through a hierarchical RNN structure composed of word-level, sentence-level and document-level representations. Experimental results suggest that the performance of the deep learning models that are trained on a single institutional dataset, are better than rule-based PEFinder on our multi-institutional test sets. The best F1 score for the presence of PE in an adult patient population was 0.99 (DPA-HNN) and for a pediatrics population was 0.99 (HNN) which shows that the deep learning models being trained on adult data, demonstrated generalizability to pediatrics population with comparable accuracy. Our work suggests feasibility of broader usage of neural network models in automated classification of multi-institutional imaging text reports for a variety of applications including evaluation of imaging utilization, imaging yield, clinical decision support tools, and as part of automated classification of large corpus for medical imaging deep learning work. | 10.1016/j.artmed.2018.11.004 |
pubmed_760_10922 | This study aimed to evaluate the tolerance to salinity and temperature, the genetic diversity and the symbiotic efficiency of rhizobia isolates obtained from wild genotypes of common bean cultivated in soil samples from the States of Goiás, Minas Gerais and Paraná. The isolates were subjected to different NaCl concentrations (0%, 1%, 2%, 4% and 6%) at different temperatures (28°C, 33°C, 38°C, 43°C and 48°C). Genotypic characterization was performed based on BOX-PCR, REP-PCR markers and 16S rRNA sequencing. An evaluation of symbiotic efficiency was carried out under greenhouse conditions in autoclaved Leonard jars. Among 98 isolates about 45% of them and Rhizobium freirei PRF81 showed a high tolerance to temperature, while 24 isolates and Rhizobium tropici CIAT899 were able to use all of the carbon sources studied. Clustering analysis based on the ability to use carbon sources and on the tolerance to salinity and temperature grouped 49 isolates, R. tropici CIAT899 and R. tropici H12 with a similarity level of 76%. Based on genotypic characterization, 65% of the isolates showed an approximately 66% similarity with R. tropici CIAT899 and R. tropici H12. About 20% of the isolates showed symbiotic efficiency similar to or better than the best Rhizobium reference strain (R. tropici CIAT899). Phylogenetic analysis of the 16S rRNA revealed that two efficient isolates (ALSG5A1 and JPrG6A8) belong to the group of strains used as commercial inoculant for common bean in Brazil and must be assayed in field experiments. | 10.1016/j.bjm.2016.09.002 |
pubmed_283_14316 | We propose that canine visceral leishmaniasis (CVL) is a systemic fibrotic disease, as evidenced by the wide distribution of fibrosis that we have found in the dogs suffering from chronic condition. The inflammatory cells apparently direct fibrosis formation. Twenty-four cases (symptomatic dogs) were identified from a total of one hundred and five cases that had been naturally infected with Leishmania chagasi and had been documented during an epidemiological survey of CVL carried out by the metropolitan area of the municipality of Belo Horizonte, MG, Brazil. The histological criterion was intralobular liver fibrosis, as has been described previously in dogs with visceral leishmaniasis. In addition to the findings in the liver, here we describe and quantify conspicuous and systemic deposition of collagen in other organs, including spleen, cervical lymph nodes, lung and kidney of all the infected symptomatic dogs. Thus we report that there is a systematic fibrotic picture in these animals, where inflammatory cells appear to direct fibrosis in all organs that have been studied. Therefore we propose that CVL is a systemic fibrotic disease. | 10.1111/iep.12010 |
pubmed_969_14615 | Our previous work on protein kinase C (PKC) and colon cancer has shown altered levels of PKC activity in human colon tumors, as well as activation of PKC by colon tumor promoters such as bile acids. To understand further the role of PKC in colon carcinogenesis, we analyzed the expression of phorbin, a gene induced by PKC activation, in a series of different stages of human colon tumors. As shown by northern blot analyses of poly (A)+ RNA, higher levels of phorbin RNA were seen in 26 colon tumor samples than in their adjacent normal colonic mucosa. There also appeared to be a correlation between the abundance of phorbin RNA in the tumors and the extent of invasion (tumor-to-normal tissue phorbin RNA ratio = 4.2, 8.0, and 11.9 for Dukes' A, B, and C, respectively). Phorbin RNA was also abundant in a human colon cancer line (HT29). We also examined the expression of other mitogen-responsive genes (c-myc, ODC, and beta-actin) in a set of 19 colon tumor samples. All tumors displayed significant (mean 3.8-fold) increases in the level of c-myc RNA compared with their adjacent normal colonic mucosa. About 47% and 16% of these tumor samples also showed increased levels of ODC (mean 3.1-fold) and beta-actin (mean 1.6-fold) RNA, respectively. The increased levels of c-myc, ODC, and beta-actin RNA did not correlate with the extent of tumor invasion. Taken together, these results demonstrate that human colon tumors usually display increased levels of both phorbin and c-myc RNAs. The marked increases in phorbin RNA suggest that this could serve as a useful biomarker in studies on human colon cancer. | 10.1002/mc.2940030204 |
pubmed_316_14420 | Propofol is a rapidly acting intravenous anesthetic agent which has many advantageous kinetic properties explaining its usefulness by bolus dose for induction of anesthesia or for administration by continuous intravenous infusion. It is rapidly distributed in the body with a half-life of only around 2 min and has an efficient hepatic and extrahepatic clearance (total body clearance may exceed liver blood flow). Premedication has little effect on the already good induction characteristics of propofol. The incidence of cardiorespiratory depression appears to be higher than that of other induction agents, but, on the other hand, the absence of tachycardiac response prevents the increase in cardiac oxygen demands. In patients with cardiac disease, especially after high or repeated doses, propofol may be more depressant to the cardiovascular system than thiopentone resulting in imbalance of regional myocardial oxygen demand and supply. Recovery from propofol is rapid and clear-headed with almost no hangover effect. This makes it very suitable for out-patient anesthesia and for cardioversion. However, even with the new emulsion formulation of the drug, pain on injection is still a problem. With regard to a longer lasting combination anesthesia propofol remains an alternative to older induction agents. When given as a continuous intravenous infusion for total intravenous anesthesia or for sedation in intensive care unit propofol has shown little accumulation. Its clinical effects are predictable, consistent and recovery is rapid, independent of the dose given. Propofol has proved to be a useful induction agent regardless of the age of patients, but in the elderly there appears to exist a marked sensitivity to it. Up to now there is no evidence that propofol in emulsion drug form can produce allergic or anaphylactoid reaction more often than other induction agents in use and no severe hematological nor visceral toxicity have been reported. In the present situation, when althesin is not marketed any more due to a high frequency of anaphylactoid reactions and etomidate will have a limited use in clinical practice because of its blocking effect on adrenocortical function, propofol offers an important alternative anesthetic agent to thiopentone. | pubmed_316_14420 |
pubmed_1115_4381 | Autism is one of a group of pervasive developmental disorders (PDD) characterized by qualitative impairments in reciprocal social communication and by a preference for repetitive, stereotyped activities, interests, and behaviors. The disorder is caused in large part by genetic mechanisms, though no disease genes have yet been identified. The objective of this study was to investigate three markers, two in the DBH gene and one in the MAO-A gene, for maternal or fetal modifier effects on level of functioning (IQ). At the same time, the possibility of maternal or fetal susceptibility effects was also examined. We assembled 67 affected sibpairs and 45 singletons and determined allele frequencies at the three markers among the affected children and first degree relatives. Sizeable and significant modifier effects were found at the MAO locus and, to a lesser extent, at the DBH locus. Susceptibility effects were also found but not without qualification. We conclude that maternal genotypes at the MAO-A locus, and possibly at the DBH one, may modify IQ in children with autism through the intrauterine environment. | 10.1002/ajmg.b.20172 |
pubmed_1074_23649 | Accumulation of misfolded proteins in the endoplasmic reticulum (ER) is the main event leading to the induction of the ER stress-related unfolded protein response (UPR). Recent postmortem evaluation, showing that the UPR pathway is activated in nigral dopaminergic neurons bearing α-synuclein inclusions in the brain of Parkinson's disease (PD) patients, suggests that the activation of the UPR may be induced by the accumulation of α-synuclein. In this study, we show that the misfolded protein-sensor/UPR activator glucose-regulated protein 78/immunoglobulin heavy chain-binding protein was bound to α-synuclein and was increased in 'in vitro' and 'in vivo' models showing aggregated α-synuclein accumulation. Moreover, α-synuclein accumulation induced the expression of the UPR-related activating transcription factor 4/cAMP-responsive element-2. These findings indicate that activation of the UPR pathway in the PD brain is associated with α-synuclein accumulation occurring in part within the ER. | 10.1111/j.1471-4159.2010.07143.x |
pubmed_567_20262 | OBJECTIVE
The purpose of this study was to evaluate the use of an echo-enhancing agent in patients with carotid artery occlusion to improve the sensitivity and specificity of carotid color flow ultrasonography.
METHOD
Between January 1997 and December 1998, a prospective study involving 85 cases of carotid artery occlusion in 84 patients was carried out. After a baseline duplex ultrasonography (DU) diagnosis, a second (DU) along with an echo-enhancement agent (SHU-508-A [Levovist]) study was carried out (echo enhancement ultrasonography diagnosis [DUEE]). In 82 cases, a contrast angiography was performed to confirm the diagnosis, whereas in the other three cases the diagnoses were confirmed with surgery.
RESULTS
From the 85 internal carotid artery occlusions diagnosed at the initial DU examination, seven came out to be false occlusions in the DUEE examination (8,2%). There was a 100% correlation of the cases between the DUEE examination and the contrast angiography in the 82 cases in which this had been done. In three of the cases, the diagnosis was confirmed surgically because these displayed severe stenoses according to the DUEE studies in symptomatic patients, and so they required urgent treatment.
CONCLUSIONS
The DUEE study is a potent diagnosis tool that allows the differentiation between true carotid artery occlusions and pseudo-occlusions. | 10.1067/mva.2000.104599 |
pubmed_742_3687 | Meprins are complex and highly glycosylated multi-domain enzymes that require post-translational modifications to reach full activity. Meprins are metalloproteases of the astacin family characterized by a conserved zinc-binding motif (HExxHxxGFxHExxRxDR). Human meprin-α and -β protease subunits are 55% identical at the amino acid level, however the substrate and peptide bond specificities vary markedly. Current work focuses on the critical amino acid residues in the non-primed subsites of human meprins-α and -β involved in inhibitor/ligand binding. To compare the molecular events underlying ligand affinity, homology modeling of the protease domain of humep-α and -β based on the astacin crystal structure followed by energy minimization and molecular dynamics simulation of fully solvated proteases with inhibitor Pro-Leu-Gly-hydroxamate in S subsites were performed. The solvent accessible surface area curve shows a decrease in solvent accessibility values at specific residues upon inhibitor binding. The potential energy, total energy, H-bond interactions, root mean square deviation and root mean square fluctuation plot reflect the subtle differences in the S subsite of the enzymes which interact with different residues at P site of the inhibitor. | 10.1080/07391102.2013.848173 |
pubmed_71_24699 | This study compares the growth of Chachi Amerindian and Afro-Ecuadorian children living in the tropical forest of northwest Ecuador. Measurements of height and weight were taken on 148 Chachi and 148 Afro-Ecuadorian children under 5 years of age. Triceps and subscapular skinfolds, arm circumference, chest circumference, and sitting height were measured on a subsample of children. Socioeconomic information was collected from the households of 145 children, and a general socioeconomic index was derived. Afro-Ecuadorian children are substantially taller than Chachi children, with significant differences in height for age z-scores in most age groups. On the other hand, Chachi children tend to have greater weight for height z-scores, with significant differences in some age groups. The greater weight for height of Chachi children may be related to their larger trunks. Estimates of body composition suggest that Afro-Ecuadorian children may have somewhat better nutritional status than Chachi children, but this does not appear to fully account for the greater height of Afro-Ecuadorian children. The socioeconomic index is positively correlated with all anthropometric dimensions, but even after controlling for the socioeconomic index, Afro-Ecuadorian children are significantly taller than Chachi children. These findings raise the possibility of genetic differences in growth potential between the two groups. © 1996 Wiley-Liss, Inc. | 10.1002/(SICI)1520-6300(1996)8:1<43::AID-AJHB4>3.0.CO;2-R |
pubmed_970_22593 | Background: Air trapping and gas exchange abnormalities are major causes of exercise limitation in chronic obstructive pulmonary disease (COPD). During incremental cardiopulmonary exercise testing, actual nadir values of ventilatory equivalents for carbon dioxide (V E/VCO 2) and oxygen (V E/VO 2) may be difficult to identify in COPD patients because of limited ventilatory compensation capacity. Therefore, we aimed in this exploratory study to detect a possible correlation between the magnitude of ventilation augmentation, as manifested by increments in ventilatory equivalents from nadir to peak exercise values and air trapping, detected with static testing. Methods: In this observational study, we studied data obtained previously from 20 COPD patients who, during routine follow-up, underwent a symptom-limited incremental exercise test and in whom a plethysmography was obtained concurrently. Air trapping at rest was assessed by measurement of the residual volume (RV) to total lung capacity (TLC) ratio (RV/TLC). Gas exchange data collected during the symptom-limited incremental cardiopulmonary exercise test allowed determination of the nadir and peak exercise values of V E/VCO 2 and V E/VO 2, thus enabling calculation of the difference between peak exrcise value and nadir values of V E/VCO 2 and V E/VO 2, designated ΔV E/VCO 2 and ΔV E/VO 2, respectively. Results: We found a statistically significant inverse correlation between both ΔV E/VCO 2 (r = -0. 5058, 95% CI -0.7750 to -0.08149, p = 0.0234) and ΔV E/VO 2 (r = -0.5588, 95% CI -0.8029 to -0.1545, p = 0.0104) and the degree of air trapping (RV/TLC). There was no correlation between ΔV E/VCO 2 and forced expiratory volume in the first second, or body mass index. Conclusions: The ventilatory equivalents increment to compensate for acidosis during incremental exercise testing was inversely correlated with air trapping (RV/TLC). | 10.12688/f1000research.20444.2 |
pubmed_1023_17807 | The evolution of crenations on the spherical red blood cell, which is part of the reversible disc-sphere transformation of these cells, is considered here. A continuum model is developed where the cell is treated as a small viscous droplet encapsulated by a viscoelastic solid membrane. When a small amount of material is deposited into the membrane, the drop responds by increasing its surface area as manifested by the appearance of ripples. A preferred number of crenations form and they are sustained for long time periods. The inception of crenations is due to a dynamic instability in the governing set of nonlinear equations, and depends on the rheological properties of the droplets' interior and membrane. | 10.1016/0022-5193(84)90034-1 |
pubmed_308_8407 | The plant plasma membrane is the interface between the cell and its environment undertaking a range of important functions related to transport, signaling, cell wall biosynthesis, and secretion. Multiple proteomic studies have attempted to capture the diversity of proteins in the plasma membrane using biochemical fractionation techniques. In this study, two-phase partitioning was combined with free-flow electrophoresis to produce a population of highly purified plasma membrane vesicles that were subsequently characterized by tandem mass spectroscopy. This combined high-quality plasma membrane isolation technique produced a reproducible proteomic library of over 1000 proteins with an extended dynamic range including plasma membrane-associated proteins. The approach enabled the detection of a number of putative plasma membrane proteins not previously identified by other studies, including peripheral membrane proteins. Utilizing multiple data sources, we developed a PM-confidence score to provide a value indicating association to the plasma membrane. This study highlights over 700 proteins that, while seemingly abundant at the plasma membrane, are mostly unstudied. To validate this data set, we selected 14 candidates and transiently localized 13 to the plasma membrane using a fluorescent tag. Given the importance of the plasma membrane, this data set provides a valuable tool to further investigate important proteins. The mass spectrometry data are available via ProteomeXchange, identifier PXD001795. | 10.1021/acs.jproteome.5b00876 |
pubmed_218_19747 | OBJECTIVE
This study tested whether coordinated care management, a continuity of care intervention for substance-use disorders, improved employment among men and women on public assistance compared with usual welfare management.
METHOD
Participants were 421 welfare applicants identified via substance-use-disorder screening and assigned via a computerized allocation program to coordinated care management (CCM; n = 232) or referral and monitoring practices in usual care (UC; n = 189). Substance use, treatment attendance, job training and search activities, and employment outcomes were assessed for 1 year after baseline.
RESULTS
Men were more likely to be working than women overall. Among women, CCM clients increased their employment over time, whereas UC clients remained stable at very low employment levels. There were no treatment effects on employment for men. Also among women only, greater substance-use-disorder treatment attendance and abstinence in the first 6 months of CCM predicted higher rates of later employment. Job training activities were low and did not differ by condition between either gender.
CONCLUSIONS
Findings are consistent with previous research supporting the effectiveness of case management for improving abstinence, which leads to employment gains, among substance-using women on public assistance. In contrast, various mandated elements of welfare-to-work programs for substance users-treatment attendance, case management, job training-did not improve employment rates for men. Implications of study results for designing effective welfare-to-work interventions in a post-welfare-reform era are discussed. | 10.15288/jsad.2009.70.955 |
pubmed_153_21879 | A wide variety of pathogens is transmitted from ticks to vertebrates including viruses, bacteria, protozoa and helminths, of which most have a life cycle that requires passage through the vertebrate host. Tick-borne infections of humans, farm and companion animals are essentially associated with wildlife animal reservoirs. While some flying insect-borne diseases of humans such as malaria, filariasis and Kala Azar caused by Leishmania donovani target people as their main host, major tick-borne infections of humans, although potentially causing disease in large numbers of individuals, are typically an infringement of a circulation between wildlife animal reservoirs and tick vectors. While new tick-borne infectious agents are frequently recognised, emerging agents of human tick-borne infections were probably circulating among wildlife animal and tick populations long before being recognised as clinical causes of human disease as has been shown for Borrelia burgdorferi sensu lato. Co-infection with more than one tick-borne infection is common and can enhance pathogenic processes and augment disease severity as found in B. burgdorferi and Anaplasma phagocytophilum co-infection. The role of wild animal reservoirs in co-infection of human hosts appears to be central, further linking human and animal tick-borne infections. Although transmission of most tick-borne infections is through the tick saliva, additional routes of transmission, shown mostly in animals, include infection by oral uptake of infected ticks, by carnivorism, animal bites and transplacentally. Additionally, artificial infection via blood transfusion is a growing threat in both human and veterinary medicine. Due to the close association between human and animal tick-borne infections, control programs for these diseases require integration of data from veterinary and human reporting systems, surveillance in wildlife and tick populations, and combined teams of experts from several scientific disciplines such as entomology, epidemiology, medicine, public health and veterinary medicine. | pubmed_153_21879 |
pubmed_1127_15952 | OBJECTIVE
The aim of this study was to better understand the knowledge of schizophrenia, preferences regarding professional help, medication and treatment methods among Australians of a Chinese-speaking background.
METHODS
A cluster convenience sampling method was adopted in which subjects were taken from the four main areas in cosmopolitan Melbourne where most Chinese people live. A total of 200 Chinese-speaking Australians participated in the study. They were presented with a vignette describing an individual with schizophrenia and were then asked questions to assess their understanding of schizophrenia and their preferences regarding professional help, medication and treatment methods. A comparative approach was used to compare our findings with those of a previous study on the mental health literacy of Australian and Japanese adults.
RESULTS
Compared with the Australian and Japanese samples, a much lower percentage of Chinese-speaking Australians (15.5%) was able to identify the vignette as a case of schizophrenia/psychosis. A higher percentage of the Chinese-speaking Australians believed that professionals, and particularly counselling professionals, could be helpful for the person in the vignette. A higher percentage of the Chinese-speaking Australian and Japanese samples believed that close family members could be helpful, and expressed more uncertainty about the usefulness or harmfulness of certain medications than the Australian sample. A higher percentage of the Chinese-speaking Australians than the Australian and Japanese samples endorsed inpatient treatment for the person in the vignette. About 22, 17, 19 and 28% of the Chinese-speaking Australian participants, respectively, rated 'traditional Chinese medical doctors', 'Chinese herbal medications', 'taking Chinese nutritional foods/supplements' and 'qiqong' as helpful. Many perceived 'changing fungshui' and 'traditional Chinese prayer' to be harmful.
CONCLUSIONS
Campaigns to increase the schizophrenia literacy of Chinese-speaking Australians are needed and must take into consideration the aforementioned socially and culturally driven beliefs so that culturally relevant education programmes can be developed. | 10.1007/s00127-009-0122-5 |
pubmed_352_5026 | In vivo glucose utilization was measured in the suprachiasmatic nuclei (SCN) of Golden hamsters using the 14C-labeled deoxyglucose technique. A circadian rhythm of SCN metabolic activity could be measured in this species, but only during pentobarbital sodium anesthesia when the surrounding background activity of adjacent hypothalamus was suppressed. Both the SCN's metabolic oscillation and its time-keeping ability are resistant to general anesthesia. | 10.1152/ajpregu.1987.252.2.R419 |
pubmed_108_2878 | Objective:To explore the clinical value of modified cricothyrotomy in the multiplane surgery under general anesthesia for patients with severe obstructive sleep apnea hypopnea syndrome(OSAHS). Method:A retrospective review was made among 20 cases with severe OSAHS treated a concurrent multiplane surgery under the condition of modified cricothyrotomy with general anesthesia, performed during recent 3 years, with their clinical data reviewed carefully. General anesthesia was carried out by inserting trachea cannula through mouth at first, and then, modified cricothyrotomy was performed via a transverse incision, followed by pulling out trachea cannula and inserting endotracheal tube through thyrocricoid incision. After this procedure, a multiplane operation was done under such a condition to treat severe OSAHS concurrently. Result:All these patients were sent back to the general ward instead of ICU after the operation, with no cervical subcutaneous emphysema occured, and one case of them bled slightly from the cervical incision during the period of hospital. Tracheal tube was pulled out successfully among these cases within 5 to 10 days. By the end of following up period for 3 months, all cervical incision of them recovered well except a dissatisfied patient due to adhesion and pull of the cervical cicatrice. After six months of follow-up, all patients were satisfied with their surgery and rehabilitation efficacy. Conclusion:Modified cricothyrotomy is easy and safe to perform, with few complications occurring and inconspicuous postoperative scar in the region of incision. Such a procedure may ensure the concurrent multiplane operation on cases with severe OSAHS performed safely as possible as it can. | 10.13201/j.issn.1001-1781.2018.22.011 |
pubmed_545_25231 | The health and well-being of childbearing women and children in the US should set a world standard. However, women and children in the US experience higher rates of morbidity and mortality than women and children in almost all other industrialized countries, with marked racial and ethnic disparities. The unfolding effects of the coronavirus disease 2019 (COVID-19) pandemic have highlighted such disparities. In this article, which is part of the National Academy of Medicine's Vital Directions for Health and Health Care: Priorities for 2021 initiative, we draw on a life-course framework to highlight promising interventions and recommend key improvements in programs and policies to optimize health and well-being among women and children in the US. The recommendations address ensuring access, transforming health care, and addressing social and environmental determinants. | 10.1377/hlthaff.2020.01504 |
pubmed_495_3235 | The somatosensory evoked potential negative components in the 100-150-ms range were studied under conditions where attention was directed either toward or away from the probe stimulus. An N120 component, not sensitive to spatial attention, appeared in all conditions, including the no-task condition. Its distribution was consistent with an origin in the second somatic area. A later N140 response, not recorded in neutral conditions, was highly sensitive to spatial attention and reached its maximum to stimulation of the attended hand; its behavior was consistent with that of a processing negativity. The N140 was bilaterally distributed, but the hemisphere contralateral to stimulation appeared to be involved earlier than the ipsilateral one. Although the exogenous N120 may be influenced by somatosensory awareness and perhaps tactile recognition, the N140 appears linked to the spatial components of attention and results from the activation of several areas in both hemispheres. | 10.1111/j.1469-8986.1995.tb01229.x |
pubmed_576_11214 | BACKGROUND
Self-administered, general health risk screening questionnaires that are administered while patients wait in the doctor's office may be a reasonable and timesaving approach to address the requirements of preventive medicine in a typical 10-min medical visit. The psychometric characteristics of the Alcohol Use Disorders Identification Test (AUDIT) incorporated within a health questionnaire (H-AUDIT) have not been examined.
METHODS
The reliability and validity of the self-administered AUDIT were compared between the H-AUDIT and the AUDIT used as a single scale (S-AUDIT) in 332 primary care patients.
RESULTS
No major demographic or alcohol use characteristics were found between the 166 subjects who completed the H-AUDIT and the 166 individuals who completed the S-AUDIT. The test-retest reliability of the 166 subjects who completed the H-AUDIT [estimated by Spearman correlation coefficient at a 6-week interval (0.88), internal consistency (total correlation coefficients for all items ranged from 0.38 to 0.69; Cronbach alpha index 0.85), and the sensitivity and specificity of the H-AUDIT were used to identify at-risk drinkers' areas under receiver operating characteristic (0.77) and alcohol-dependent subjects' areas under receiver operating characteristic (0.89)] was similar to the same measurements obtained with the 166 individuals who completed the S-AUDIT.
CONCLUSIONS
The AUDIT incorporated in a health risk screening questionnaire is a reliable and valid self-administered instrument to identify at-risk drinkers and alcohol-dependent individuals in primary care settings. | pubmed_576_11214 |
pubmed_245_305 | BACKGROUND
In an ageing Europe, chronic pain is a major public health problem, but robust epidemiological data are scarce. This study aimed to analyse the prevalence of and factors associated with chronic musculoskeletal pain by gender in older adults of 14 European countries.
METHODS
A cross-sectional study was performed from wave 5 of the Survey of Health, Ageing and Retirement in Europe (SHARE). The study included people ≥50 years residing in Austria, Belgium, Czech Republic, Denmark, Estonia, France, Germany, Italy, Luxembourg, the Netherlands, Slovenia, Spain, Sweden and Switzerland. Chronic pain was defined as being bothered by joint and/or back pain for the previous 6 months. Multivariable Poisson regression models with robust variance were performed to analyse prevalence ratio by covariates, stratified by sex.
RESULTS
A total of 61,157 participants were included. Overall prevalence of chronic musculoskeletal pain was 35.7% (28.8-31.7), ranging from 18.6% (17.1-20.1) for Switzerland to 45.6% (43.3-47.8) for France. Prevalence was higher in women than in men: 41.3% (40.2-42.4) versus 29.1% (28.0-30.3). Chronic musculoskeletal pain was lower in men aged >75 years (PR = 0.82; 0.72-0.92) than the younger (50-59) group. Separated/divorced status presented opposite effects among men (PR = 0.85; 0.76-0.96) and women (PR = 1.12; 1.03-1.21) compared with married, and unemployment was a significant factor in men (PR = 1.21; 95% CI 1.02-1.43) compared with employed.
CONCLUSIONS
Musculoskeletal pain in older European adults is very frequent, especially in women, with large differences depending on the country of residence. Health policy makers should prioritize strategies aimed at improving the prevention and management of chronic musculoskeletal pain in Europe.
SIGNIFICANCE
This study provides epidemiological data of chronic musculoskeletal pain in older adults. Reported differences contribute to highlight the relevance of considering a gender perspective in chronic musculoskeletal pain research. Cross-national comparison also offers a map of differences that improves the knowledge of this chronic condition in Europe. | 10.1002/ejp.1123 |
pubmed_483_17364 | BACKGROUND
Media can influence public and policy-makers' perceptions of causes of, and solutions to, public health issues through selective presentation and framing. Childhood obesity is a health issue with both individual-level and societal-level drivers and solutions, but public opinion and mass media representations of obesity have typically focused on individual-level framings, at the cost of acknowledgement of a need for regulatory action.
OBJECTIVE AND SETTING
To understand the salience and framing of childhood obesity across 19 years of UK national newspaper content.
DESIGN AND OUTCOME MEASURES
Quantitative content analysis of 757 articles about childhood obesity obtained from six daily and five Sunday newspapers. Articles were coded manually for definitions, drivers and potential solutions. Data were analysed statistically, including analysis of time trends and variations by political alignment of source.
RESULTS
The frequency of articles grew from a low of two in 1996 to a peak of 82 in 2008, before declining to 40 in 2010. Individual-level drivers (59.8%) and solutions (36.5%) were mentioned more frequently than societal-level drivers (28.3%) and solutions (28.3%) across the sample, but societal solutions were mentioned more frequently during the final 8 years, coinciding with a marked decline in yearly frequency of articles.
CONCLUSIONS
Increased focus on societal solutions aligns with public health goals, but coincided with a reduction in the issue's salience in the media. Those advocating public policy solutions to childhood obesity may benefit from seeking to raise the issue's media profile while continuing to promote structural conceptualisations of childhood obesity. | 10.1136/bmjopen-2018-025646 |
pubmed_1104_16348 | The phylogenetic relationships between the two southern hemisphere lamprey families (Geotriidae and Mordaciidae) and their northern hemisphere counterparts (Petromyzontidae) are unresolved. Insulin was isolated from an extract of islet-containing intestinal tissue from ammocoetes of the Australian lamprey, Mordacia mordax. Its primary structure was established as A-chain: GIVEQCCHRK10CSIYDMENYC20N and B-chain: SALMGTGGTH10LCGSHLVEAL20YVVCGQRGFF30 YTP[SKG]. Although the residues in parentheses are only tentatively assigned, mass spectrometry supports the proposed sequence and demonstrates that Mordacia proinsulin, unlike proinsulin from Geotria australis, is fully processed to mature insulin. Insulins from M. mordax and G. australis and from the northern hemisphere lampreys Petromyzon marinus and Lampetra fluviatilis share a pentapeptide extension to N-terminus of the B-chain (Ser-Ala-Leu-Xaa-Gly) that has never been found in the insulins of any other vertebrate class. This observation provides support for the claim that the Petromyzontiformes constitute a monophyletic group. M. mordax insulin differs from that of G. australis by 18 amino acid residues but by only four residues from the common sequence of P. marinus and L. fluviatilis insulin. These data are consistent with the view that Geotriidae and Mordaciidae have been separated for a long period and suggest that G. australis insulin has undergone an accelerated rate of molecular evolution. | 10.1016/s1096-4959(00)00365-1 |
pubmed_172_17780 | Angiotensin II stimulates prostaglandin (PG) E2 formation in mesangial cells cultured from rat renal glomeruli. The interactions between angiotensin II and PGE2 are important in modulating glomerular function. We examined the mechanism for stimulation of PGE2 production in mesangial cells using the putative diacylglycerol-lipase inhibitor RHC 80267 and trifluoperazine (TFP), an agent interfering with Ca2+-CaM-mediated processes. Although RHC 80267 inhibited diacylglycerol-lipase activity in mesangial cells, it did not influence PGE2 production in response to either angiotensin II or A23187. In contrast, TFP (50 microM) inhibited basal PGE2 production and stimulation by angiotensin II and A23187. TFP also decreased 14C release in response to angiotensin from cells prelabeled with [14C]arachidonic acid, which was associated with inhibition of 14C loss from phosphatidylinositol. In cells prelabeled with 32P, orthophosphate angiotensin II caused a rapid hydrolysis of phosphatidylinositol 4,5-bisphospate. TFP enhanced 32P labeling of phosphatidylinositides, but did not prevent the loss of phosphatidylinositol 4,5-bisphosphate in response to angiotensin. This was verified in cells prelabeled with myo-[3H]inositol where angiotensin stimulated formation of [3H]inositol trisphosphate. TFP enhanced formation of [3H]inositol trisphosphate both under basal- and angiotensin II-stimulated conditions. Thus TFP did not inhibit phospholipase C activation by angiotensin. Angiotensin II caused marked increases in [32P]lysophospholipids, indicating activation of also phospholipase A2. This process was inhibited by TFP. Taken together, these results are consistent with stimulation of both phospholipase C and A2 by angiotensin, the latter step responsible for the release of arachidonic acid and PGE2 formation. The activation of phospholipase A2, but not that of phospholipase C, is inhibited by TFP, perhaps by interference with calmodulin-dependent steps. | 10.1152/ajpcell.1987.253.1.C113 |
pubmed_943_18547 | 1. The aim of this study was to compare the effects of chronic treatment (for 4 or 7 days) with nicotinic drugs and 20 mM KCl on numbers of surface alpha7 nicotinic AChR, identified by [(125)I]-alpha bungarotoxin (alpha-Bgt) binding, in primary hippocampal cultures and SH-SY5Y cells. Numbers of alpha3* nicotinic AChR were also examined in SH-SY5Y cells, using [(3)H]-epibatidine, which is predicted to label the total cellular population of predominantly alpha3beta2* nicotinic AChR under the conditions used. 2. All the nicotinic agonists examined, the antagonists d-tubocurarine and methyllycaconitine, and KCl, upregulated [(125)I]-alpha Bgt binding sites by 20 - 60% in hippocampal neurones and, where examined, SH-SY5Y cells. 3. Upregulation of [(125)I]-alpha-Bgt binding sites by KCl was prevented by co-incubation with the L-type Ca2+ channel blocker verapamil or the Ca2+-calmodulin dependent kinase II (CaM-kinase II) inhibitor KN-62. Upregulation of [(125)I]-alpha-Bgt binding sites by nicotine or 3,[(4-dimethylamino) cinnamylidene] anabaseine maleate (DMAC) was insensitive to these agents. 4. [(3)H]-Epibatidine binding sites in SH-SY5Y cells were not affected by KCl but were upregulated in a verapamil-insensitive manner by nicotine and DMAC. KN-62 itself provoked a 2 fold increase in [(3)H]-epibatidine binding. The inactive analogue KN-04 had no effect, suggesting that CaM-kinase II plays a role in regulating numbers of alpha3* nicotinic AChR. 5. These data indicate that numbers of alpha3* and alpha7 nicotinic AChR are modulated differently. Nicotinic agonists and KCl upregulate alpha7 nicotinic AChR through distinct cellular mechanisms, the latter involving L-type Ca2+ channels and CaM-kinase II. In contrast, alpha3* nicotinic AChR are not upregulated by KCl. This difference may reflect the distinct physiological roles proposed for alpha7 nicotinic AChR. | 10.1038/sj.bjp.0704207 |
pubmed_242_4195 | Since the introduction of anti-tumor necrosis factor (TNF) therapy as treatment of inflammatory bowel disease (IBD), care of pediatric and adult patients with IBD has significantly improved. To further improve treatment efficacy and durability, multiple trials have compared the efficacy of combination therapy, using anti-TNF therapy combined with an immunomodulator (a thiopurine or methotrexate), with that of anti-TNF monotherapy with contradicting results. The safety of combined therapy has been questioned after several reported cases of hepatosplenic T-cell lymphoma in young patients with IBD so treated. Physicians prescribing anti-TNF therapy to patients with IBD are required to weigh the benefits of combined therapy with its risks. To inform physicians treating children with IBD of these benefits and risks, we reviewed studies in pediatric and adult patients with IBD comparing efficacy, durability, and/or safety of combined therapy with anti-TNF monotherapy. | 10.1097/MIB.0000000000000245 |
pubmed_42_2043 | PURPOSE
To report the youngest case of retinal arterial macroaneurysm.
METHOD
Case Report.
RESULTS
Clinical examination and fundus fluoroscein angiography revealed retinal arterial macroaneurysm in a 23-year-old patient with chronic renal failure.
CONCLUSIONS
Acquired macroaneurysm may develop even in a very young patient, especially with chronic renal failure. | 10.1177/112067210001000314 |
pubmed_969_16387 | The effects of epidermal growth factor (EGF) on androgen stimulation of accessory sex gland growth and biochemistry were determined for prepubertal male Swiss-Webster mice. For the seminal vesicle and anterior prostate, 5 alpha dihydrotestosterone (5 alpha DHT) treatment significantly increased the quantitative levels of organ wet weight, DNA content, polyamine content, and stereologically determined epithelium and lumen volumes above the control group. EGF treatment alone slightly enhanced the levels of most measured parameters from control values. However, when a combined EGF&5 alpha DHT treatment was compared with 5 alpha DHT treatment alone, the 5 alpha DHT treatment effects on epithelial and lumen volumes and polyamine content were antagonized by the action of EGF. | 10.1002/pros.2990160403 |
pubmed_24_7484 | Mentoring is an important teaching-learning process in undergraduate nursing curricula. There are relatively few studies specifically evaluating nursing students' perceptions of mentorship. In the period 1999-2002, 39 students were mentored during a year-long program. This descriptive, exploratory study used a quality improvement framework informed by the Deming cycle of Plan, Do, Check and Act [Deming, W.E., 1982. Quality, Productivity and Competitive Position. Massachusetts Institute of Technology, Cambridge] to evaluate the mentorship program from the students' perspective. Information was gathered through surveys, focus group discussions and interviews and analyzed to identify themes of responses. Identified themes were 'The doing of nursing', 'The thinking of nursing' and 'Being a nurse'. The study confirmed the value of mentorship in undergraduate nursing and highlighted the importance of skill competence as a basis for professional role identity by graduating students. The benefits of mentorship were derived from a long term, supportive relationship with the same registered nurse who was committed to the student's professional development. | 10.1016/j.nedt.2006.01.009 |
pubmed_511_3885 | During the response to the Fukushima Daiichi nuclear power plant (FDNPP) emergency, about 50 patients died during or shortly after an evacuation when they were not provided with the needed medical support. In addition, it has been shown that during the FDNPP emergency there were increases in mortality rates among the elderly due to long-term dislocation as a result of evacuation and relocation orders and an inability to stay in areas where residents were advised to shelter for extended periods. These deaths occurred even though the possible radiation exposure to the public was too low to result in radiation-induced deaths, injuries, or a meaningful increase in the cancer rate, even if no protective actions had been taken. These problems are not unique to the FDNPP emergency and would be expected if the recommendations of many organizations were followed. Neither the International Commission on Radiological Protection (ICRP), the U.S. Nuclear Regulatory Commission (NRC) nor the U.S Environmental Protection Agency (EPA) adequately take into consideration in their recommendations and analysis the non-radiological health impacts, such as deaths and injuries, that could result from protective actions. Furthermore, ICRP, NRC, EPA, and the U.S. Department of Homeland Security (DHS) call for taking protective actions at doses lower than those resulting in meaningful adverse radiation-induced health effects and do not state the doses at which such effects would be seen. Consequently, it would be impossible for decision makers and the public to balance all the hazards both from radiation exposure and protective actions when deciding whether a protective action is justified. What is needed, as is presented in this paper, is a method for developing a comprehensive protective action strategy that allows the public, decision makers, and others who must work together to balance the radiological with the non-radiological health hazards posed by protective actions, and to counter the exaggerated fear of radiation exposure that could lead to taking unjustified protective actions and adverse psychological, sociological, and other effects. | 10.1097/HP.0000000000000801 |
pubmed_1121_1600 | To understand impact of input and output parameters during optimization and degree of complexity, in the current study we numerically designed a bubble column reactor with a single sparger in the middle of the reactor. After that, some input and output parameters were selected in the post-processing of the numerical method, and then the machine learning observation started to investigate the level of complexity and impact of each input on output parameters. The adaptive neuro-fuzzy inference system (ANFIS) method was exploited as a machine learning approach to analyze the gas-liquid flow in the reactor. The ANFIS method was used as a machine learning approach to simulate the flow of a 3D (three-dimensional) bubble column reactor. This model was also used to analyze the influence of input and output parameters together. More specifically, by analyzing the degree of membership functions as a function of each input, the level of complexity of gas fraction was investigated as a function of computing nodes (X, Y, and Z directions). The results showed that a higher number of membership functions results in a better understanding of the process and higher model accuracy and prediction capability. X and Y computing nodes have a similar impact on the gas fraction, while Z computing points (height of reactor) have a uniform distribution of membership function across the column. Four membership functions (MFs) in each input parameter are insufficient to predict the gas fraction in the 3D bubble column reactor. However, by adding two membership functions, all features of gas fraction in the 3D reactor can be captured by the machine learning algorithm. Indeed, the degree of MFs was considered as a function of each input parameter and the effective parameter was found based on the impact of MFs on the output. | 10.1038/s41598-021-81514-y |
pubmed_594_19418 | Cocaine or air jet stress evokes pressor responses due to either a large increase in systemic vascular resistance (vascular responders) or small increases in both cardiac output and vascular resistance (mixed responders) in conscious rats. Repeated cocaine administration results in elevated arterial pressure in vascular responders but not in mixed responders. The present study examined the hypothesis that the pattern of cardiovascular responses to an unconditioned stimulus (UCS; air jet) is related to responses to a conditioned stimulus (CS; tone followed by brief foot shock) in individual rats. Our data demonstrate that presentation of the UCS produced variable cardiac output responses that correlated with responses to the CS (n = 60). We also determined whether individual cardiovascular response patterns to acute stress correlated with predisposition to a sustained stress-induced elevation in arterial pressure. Rats were exposed to three different stressors presented one per day successively for 4 wk and during a poststress period of 3 wk while arterial pressure was recorded periodically. Mean arterial pressure was elevated in all rats during chronic stress but, during the poststress period, remained at significantly higher levels in vascular responders but not mixed responders. Therefore, we conclude that acute behavioral stress to a conditioned stimulus elicits variable hemodynamic responses that predict the predisposition to a sustained stress-induced elevation in arterial pressure. | 10.1152/ajpregu.2001.281.1.R31 |
pubmed_707_21585 | BACKGROUND AND PURPOSE
Dose painting by numbers (DPBN) require a high degree of dose modulation to fulfill the image-based voxel wise dose prescription. The aim of this study was to assess the dosimetric accuracy of 18F-fluoro-2-deoxy-glucose positron emission tomography(18F-FDG-PET)-based DPBN in an anthropomorphic lung phantom using alanine dosimetry.
MATERIALS AND METHODS
A linear dose prescription based on 18F-FDG-PET image intensities within the gross tumor volume (GTV) of a lung cancer patient was employed. One DPBN scheme with low dose modulation (Scheme A; minimum/maximum fraction dose to the GTV 2.92/4.26 Gy) and one with a high modulation (Scheme B; 2.81/4.52 Gy) were generated. The plans were transferred to a computed tomograpy (CT) scan of a thorax phantom based on CT images of the patient. Using volumetric modulated arc therapy (VMAT), DPBN was delivered to the phantom with embedded alanine dosimeters. A plan was also delivered to an intentionally misaligned phantom. Absorbed doses at various points in the phantom were measured by alanine dosimetry.
RESULTS
A pointwise comparison between GTV doses from prescription, treatment plan calculation and VMAT delivery showed high correspondence, with a mean and maximum dose difference of <0.1 Gy and 0.3 Gy, respectively. No difference was found in dosimetric accuracy between scheme A and B. The misalignment caused deviations up to 1 Gy between prescription and delivery.
CONCLUSION
DPBN can be delivered with high accuracy, showing that the treatment may be applied correctly from a dosimetric perspective. Still, misalignment may cause considerable dosimetric erros, indicating the need for patient immobilization and monitoring. | 10.1016/j.phro.2022.02.013 |
pubmed_315_21904 | The identification of general principles relating structure to dynamics has been a major goal in the study of complex networks. We propose that the special case of linear network dynamics provides a natural framework within which a number of interesting yet tractable problems can be defined. We report the emergence of modularity and hierarchical organization in evolved networks supporting asymptotically stable linear dynamics. Numerical experiments demonstrate that linear stability benefits from the presence of a hierarchy of modules and that this architecture improves the robustness of network stability to random perturbations in network structure. This work illustrates an approach to network science which is simultaneously structural and dynamical in nature. | 10.1103/PhysRevLett.92.188701 |
pubmed_1055_12534 | PURPOSE
This study aimed to examine the risk factors of probable sudden unexpected death in epilepsy (SUDEP) among patients with convulsive epilepsy in rural communities.
METHOD
A total of 35 cases with identified probable SUDEP were recruited in the study and compared with three survival controls that were sex and age matched from the same cohort for each case. Three healthy controls per case were chosen as a control group. Risk factors were analyzed using the logistic regression model. The odds ratio (OR) was calculated to determine the risk or protective effect.
RESULTS
The following three factors significantly increased the risk of probable SUDEP: early-onset age of seizures (≤10 years vs. >10 years) with an OR of 6.8 (95% CI: 1.5-32.6), high seizure frequency at baseline (>10 years vs. ≤10 years) before regular phenobarbital treatment with an OR of 5.9 (95% CI: 2.2-16.6), and experiencing one or more seizures (vs. seizure-free) in the month prior to probable SUDEP with an OR of 9.5 (95% CI: 3.0-30.1).
CONCLUSION
Lack of seizure freedom before and during regular antiepileptic drug treatment increase the risk of probable SUDEP. Special attention should be given to patients with early convulsive epilepsy-onset, and the proper control of convulsive seizures is critical for the prevention of probable SUDEP. | 10.1016/j.seizure.2016.05.002 |
pubmed_114_13619 | The activity of SAS 650, a new anti-inflammatory drug, on ex vivo and in vitro MDA production by platelets was compared to that of aspirin. The drug induced dose-dependent inhibition of in vitro MDA production by rat and guinea-pig platelets and also had good activity after 30 second of incubation in rat platelets, quicker than aspirin. SAS 650 preincubation reduced the in vitro inhibitory effect of ASA, as shown also by ex vivo experiments. The results of the present study support the involvement of SAS 650 in the platelet cyclooxygenase pathway. | 10.1007/BF01978917 |
pubmed_789_15901 | OBJECTIVES
This study explores the views of older adults who are receiving health and social care at the end of their lives, on how services should be funded, and describes their health-related expenditure.
DESIGN
Qualitative interview study.
SETTING
North West England.
PARTICIPANTS
30 people aged 69-93 years, diagnosed with lung cancer, heart failure or stroke and judged by health professionals to be in their last year of life. Sixteen participants lived in disadvantaged areas.
MAIN OUTCOME MEASURES
Views of older adults on funding of services.
RESULTS
Participants expressed a belief in an earned entitlement to services funded from taxation, based on a broad sense of being a good citizen. Irrespective of social background, older people felt that those who could afford to pay for social care, should do so. Sale of assets and use of children's inheritance to fund care was widely perceived as an injustice. The costs of living with illness are a burden, and families are filling many of the gaps left by welfare provision. People who had worked in low-wage occupations were most concerned to justify their current acceptance of services, and distance themselves from what they described as welfare 'spongers' or 'layabouts.'
CONCLUSIONS
There is a gap between the health and social care system that older adults expect and what may be provided by a reformed welfare state at a time of financial stringencies. The values that underpinned the views expressed--mutuality, care for the most needy, and the importance of working to contribute to society--are an important contribution to the debate on welfare funding. | 10.1258/jrsm.2012.110189 |
pubmed_21_20034 | The effects of copper on germination and growth of fenugreek (Trigonella foenum-graecum) was investigated separately using different concentrations of CuSO₄. The germination percentage and radical length had different responses to cupric ions: the root growth increased with increasing copper concentration up to 1 mM Cu²⁺ and was inhibited thereafter. In contrast, the germination percentage was largely unaffected by concentrations of copper below 10 mM. The reduction in root growth may have been due to inhibition of hydrolytic enzymes such as amylase. Indeed, the average total amylolytic activity decreased from the first day of treatment with [Cu²⁺] greater than 1 mM. Furthermore, copper affected various plant growth parameters. Copper accumulation was markedly higher in roots as compared to shoots. While both showed a gradual decrease in growth, this was more pronounced in roots than in leaves and in stems. Excess copper induced an increase in the rate of hydrogen peroxide (H₂O₂) production and lipid peroxidation in all plant parts, indicating oxidative stress. This redox stress affected leaf chlorophyll and carotenoid content which decreased in response to augmented Cu levels. Additionally, the activities of proteins involved in reactive oxygen species (ROS) detoxification were affected. Cu stress elevated the ascorbate peroxidase (APX) activity more than two times at 10 mM CuSO₄. In contrast, superoxide dismutase (SOD) and catalase (CAT) levels showed only minor variations, only at 1 mM Cu²⁺. Likewise, total phenol and flavonoid contents were strongly induced by low concentrations of copper, consistent with the role of these potent antioxidants in scavenging ROS such as H₂O₂, but returned to control levels or below at high [Cu²⁺]. Taken together, these results indicate a fundamental shift in the plant response to copper toxicity at low versus high concentrations. | pubmed_21_20034 |
pubmed_595_16550 | Rate constants and binding constants for the alpha-chymotrypsin-catalyzed hydrolysis of N-acetyltyrosine, tryptophan, and phenylalanine anilides are presented. Both k(cat) and K(m) are independent of electronic effects in the substrate over a range of 9.8 orders of magnitude (as measured by pK of the leaving group). Similarly, K(m) is independent of charge and orientation about the alpha-carbon for various substrates and pseudo-substrates. These results are not consistent with the pretransition state protonation hypothesis; instead, they are discussed in terms of a tetrahedral intermediate that is thermodynamically less stable than the Michaelis complex. | 10.1073/pnas.70.2.517 |
pubmed_201_18381 | Innovative empirical frameworks to evaluate progress in efforts addressing HIV treatment and prevention barriers in resource-limited areas are sorely needed to achieve the UNAIDS 90-90-90 goal (90% diagnosed, 90% on treatment, and 90% virally suppressed). A triadic implementation framework (TIF) is a comprehensive conceptual tool for (1) monitoring attrition, (2) evaluating operational programs, and (3) measuring the impact of specific implementation goals within the care continuum. TIF will assess the effects of enhanced programs on adherence and virologic suppression within the HIV care continuum at a regional clinic in the Dominican Republic (Clínica de Familia La Romana [CFLR]) and its program serving high-risk, migratory batey (sugarcane cultivation) communities. A retrospective cohort study completed during 2015 collected deidentified data from a CFLR chart review of adult HIV patients diagnosed in 2013. The results were quantitatively analyzed and compared to 2011 cohort data. In 2013, 310 patients were diagnosed HIV positive. The results demonstrated 73% enrolling in care, 28% adhering to care, and 16% achieving viral load suppression. Engagement increased across all steps of the care continuum compared to a 2011 cohort, culminating in a significant increase in undetectable viral load from 4% to 16% (p < 0.001). The batey program showed significant increases in patient enrollment compared to the 2011 cohort (p < 0.001). Meeting the UNAIDS 90-90-90 goal requires enhanced services in high-burden, resource-limited regions. CFLR employs TIF to assess progress and programmatic areas in need of strengthening. Data suggest enhanced CFLR services improve outcomes. Given improvements, maintenance and expansion of similar programs are warranted to achieve the 90-90-90 goal. | 10.1089/apc.2017.0118 |
pubmed_799_8081 | PURPOSE
The purpose of this study was to investigate pain management among 42 hospice and 65 non-hospice residents in two proprietary nursing homes.
DESIGN AND METHODS
In this prospective, anthropological, quantitative, and qualitative study, we used participant observation, event analysis, and chart review to obtain data. The Medication Quantification Scale was used in order to account for the prescription and administration of all analgesic medications.
RESULTS
Although 72% of residents experienced pain, we found no statistically significant differences in the proportion of hospice versus non-hospice residents (a) who had been prescribed opioids and co-analgesics, and (b) whose medication was administered around the clock or as needed. Limited physician availability, lack of pharmacologic knowledge, and limitations of nursing staff hindered pain management of both groups of residents.
IMPLICATIONS
Although hospice care is of some benefit, pain management and high-quality end-of-life care is dependent upon the context in which it is provided. Given that between 1991 and 2001 Medicare expenditures for nursing home-based hospice care increased from dollar 8.6 million to dollar 21.8 million, the effectiveness of hospice-care programs in nursing homes warrants further study. | 10.1093/geront/46.3.325 |
pubmed_81_21531 | The patient positioning and repositioning control in radiation therapy all along the treatment can be conducted using a variety of X-ray sources and imaging detector devices. The development of image guided radiation therapy techniques leads to more frequent use of this imaging control. In this article we summarize the current methods for measuring the dose delivered by X-ray imaging devices used in radiation therapy, as well as basic proposals to take account of these imaging doses for prescribing, recording and reporting radiation therapy treatment. | 10.1016/j.canrad.2008.05.006 |
pubmed_293_14016 | A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper. | 10.1038/s41598-019-43789-0 |
pubmed_120_21044 | An L-amino acid oxidase (TM-LAO) from the venom of Hunan Trimeresurus mucrosquamatus was purified to homogeneity by three steps including DEAE Sephadex A-50 ion-exchange chromatography, Sephadex G-75 gel filtration and Resource Q ion-exchange chromatography. TM-LAO is composed of two identical subunits with a molecular weight of 55 kD by SDS-polyacrylamide gel electrophoresis. The molecular weight was different with that of LAO purified from the same species distributed in Taiwan that was 70 kD. The 24 N-terminal amino acid sequence of TM-LAO is ADNKNPLEECFRETNYEEFLEIAR, which shares high similarity with other Viperid snake venom LAOs and has moderate similarity with Elapid snake venom LAOs. Further studies found that TM-LAO inhibited the growth of E. coli, S. aurues and B. dysenteriae. TM-LAO also showed cytotoxicity and platelet aggregation activity. All the biological activities were eliminated by catalase, a H(2)O(2) scavenger. It was shown that these biological effects were possibly due to the formation of H(2)O(2) produced by TM-LAO. | pubmed_120_21044 |
pubmed_176_23893 | BACKGROUND AND AIMS
We aimed to determine the effects on glycemic responses and potential risk of hypoglycaemia in type 1 diabetic subjects of replacing half the starch in a meal with sugars, and of adding fat to the low-sugar and high-sugar meals.
METHODS AND RESULTS
We studied overnight fasted subjects with type 1 diabetes (n = 11) and age-, BMI- and ethnicity-matched controls (n = 11) using a 2 × 2 factorial design. The low-sugar/low-fat meal was 110 g white-bread. In the high-sugar/low-fat meal half the white-bread starch replaced by sugars (jam and orange juice). The high-fat meals consisted of the low-fat meals plus 20 g fat (margarine). The significance of the main effects of sugars and fat and the sugar × fat, group × sugar and group × fat interactions were determined by ANOVA. In control and diabetic subjects, respectively, high-sugar significantly reduced time to peak rise by 13% (P = 0.004) and 32% (P = 0.004; group × sugar: P = 0.01) and increased peak rise by 14% and 10% (ns). Adding fat increased time to peak rise by 17-19% in both groups (P = 0.003), reduced peak rise by 31% in normal (P < 0.001) but increased peak rise in diabetic subjects by 3% (ns) (group × fat: P = 0.022). Blood glucose nadir and occurrence of hypoglycaemia were similar among the 4 meals.
CONCLUSIONS
In type 1 diabetes, insulin adjustment to avoid hypoglycemia may be useful for meals in which the proportion of carbohydrate absorbed as glucose is <0.75, however the precise level which increases hypoglycaemic risk requires further research. The results suggest that people with type 1 diabetes should not be advised to add fat to meals to reduce glycemic responses. | 10.1016/j.numecd.2010.12.005 |
pubmed_488_2168 | Keratomalacia occurred in two cachectic hospitalized patients, each with severe vitamin A-protein deficiency secondary to a lethal disease. Prompt therapy with parenteral and topical vitamin A, protein supplementation, and a soft contact lens restored corneal integrity and prevented visual loss in one patient. Keratinization of the conjunctiva did not occur in either patient. Patients with severe protein deficiency may develop keratomalacia in the absence of a severely decreased serum level of vitamin A. | 10.1016/0002-9394(76)90491-8 |
pubmed_713_12687 | The way people make career choices is often influenced by their idea of work. Alongside this concept, there is the idea of decent work, which takes the form of the opportunity, for men and women, to have productive, equal, safe, and rights-based work. We have conducted a study on these two concepts with a group of Italian adolescents, using both quantitative and qualitative methods. We found that most of the participants consider work as a means to obtain economic benefits and satisfy certain values, and decent work as characterized by the respect for rights and duties and economic benefits; a part of the participants fails in giving a definition of decent work or gives a negative definition of it. We deepened the study through quantitative analyses that revealed that those who have a more complex view of work and decent work also have higher levels of self-efficacy and career adaptability. These findings are discussed in the light of previous research and from a perspective that intends to give a contribution to career counseling practices. | 10.3389/fpsyg.2021.660721 |
pubmed_118_14119 | The approach to rehabilitation of upper extremity injuries in athletes differs from traditional rehabilitation protocols. In general, athletes have higher functional demands and wish to return to competitive sport in a timely manner. Comprehensive rehabilitation must therefore be balanced with a timely and safe return to sport. Several rehabilitation programs and adjunctive therapies are available to hasten convalescence while minimizing the athlete's risks of reinjury. Here, we review techniques for soft tissue mobilization and strength training in athletic populations. We also discuss orthotics, taping, and alternative therapies used in rehabilitation and evaluate the evidence in support of these modalities. | 10.1016/j.hcl.2016.08.016 |
pubmed_916_20844 | Microfluidic technologies enable in vitro studies to closely simulate in vivo microvessel environment with complexity. Such method overcomes certain constrains of the statically cultured endothelial monolayers and enables the cells grow under physiological range of shear flow with geometry similar to microvessels in vivo. However, there are still existing knowledge gaps and lack of convincing evidence to demonstrate and quantify key biological features of the microfluidic microvessels. In this paper, using advanced micromanufacturing and microfluidic technologies, we presented an engineered microvessel model that mimicked the dimensions and network structures of in vivo microvessels with a long-term and continuous perfusion capability, as well as high-resolution and real-time imaging capability. Through direct comparisons with studies conducted in intact microvessels, our results demonstrated that the cultured microvessels formed under perfused conditions recapitulated certain key features of the microvessels in vivo. In particular, primary human umbilical vein endothelial cells were successfully cultured the entire inner surfaces of the microchannel network with well-developed junctions indicated by VE-cadherin staining. The morphological and proliferative responses of endothelial cells to shear stresses were quantified under different flow conditions which was simulated with three-dimensional shear dependent numerical flow model. Furthermore, we successfully measured agonist-induced changes in intracellular Ca2+ concentration and nitric oxide production at individual endothelial cell levels using fluorescence imaging. The results were comparable to those derived from individually perfused intact venules. With in vivo validation of its functionalities, our microfluidic model demonstrates a great potential for biological applications and bridges the gaps between in vitro and in vivo microvascular research. | 10.1371/journal.pone.0126797 |
pubmed_828_11584 | BACKGROUND & AIMS
Saturated free fatty acids induce hepatocyte lipoapoptosis. This lipotoxicity involves an endoplasmic reticulum stress response, activation of JNK, and altered expression and function of Bcl-2 proteins. The mono-unsaturated free fatty acid palmitoleate is an adipose-derived lipokine which suppresses free fatty acid-mediated lipotoxicity by unclear mechanisms. Herein we examined the mechanisms responsible for cytoprotection.
METHODS
We employed isolated human and mouse primary hepatocytes, and the Huh-7 and Hep 3B cell lines for these studies. Cells were incubated in presence and absence of palmitate (16:0), stearate (18:0), and or palmitoleate (16:1, n-7).
RESULTS
Palmitoleate significantly reduced lipoapoptosis by palmitate or stearate in both primary cells and cell lines. Palmitoleate accentuated palmitate-induced steatosis in Huh-7 cells excluding inhibition of steatosis as a mechanism for reduced apoptosis. Palmitoleate inhibited palmitate induction of the endoplasmic reticulum stress response as demonstrated by reductions in CHOP expression, eIF2-alpha phosphorylation, XBP-1 splicing, and JNK activation. Palmitate increased expression of the BH3-only proteins PUMA and Bim, which was attenuated by palmitoleate. Consistent with its inhibition of PUMA and Bim induction, palmitoleate prevented activation of the downstream death mediator Bax.
CONCLUSIONS
These data suggest palmitoleate inhibits lipoapoptosis by blocking endoplasmic reticulum stress-associated increases of the BH3-only proteins Bim and PUMA. | 10.1016/j.jhep.2010.01.003 |
pubmed_1081_14887 | Chikungunya virus (CHIKV) is an arbovirus transmitted by Aedes mosquitoes that was first identified in Brazil in 2014. It causes a febrile illness characterised by severe arthralgia and rash. Our group investigated a suspected CHIKV outbreak in Governador Valadares, state of Minas Gerais, Brazil and from 25 acute-phase patients, 10 had qRT-PCR positive sera samples and had E1 partial sequence amplified and Sanger sequenced. Samples were identified as East/Central/South African (ECSA) genotype by phylogenetic analysis and clustered with CHIKV sequences isolated in the neighbour state of Bahia. Our findings confirm previous predictions that ECSA genotype would spread through northeast and southeast of Brazil. | 10.1017/S0950268818002467 |
pubmed_189_18826 | OBJECTIVE
To determine associations between Thai fathers' self-efficacy to support exclusive breastfeeding and exclusive breastfeeding duration.
DESIGN
A descriptive quantitative design was used.
PARTICIPANTS AND SETTINGS
The study sample consisted of 205 father-mother couples (410 participants) with an infant who was 6 months old. Data were conducted from well-baby clinics of two hospitals in Thailand's Chiang Mai province from January to March 2020.
MEASUREMENT
Each participant completed a sociodemographic questionnaire and Breastfeeding Self-Efficacy Scale (Short-Form). Father participants also completed the Father's Attitude toward Exclusive Breastfeeding questionnaire.
FINDINGS
Bivariate correlation analyses of survey data showed that paternal and maternal breastfeeding self-efficacy scores were positively associated with longer duration of exclusive breastfeeding (ρ=0.19 and ρ=0.54, respectively). Paternal self-efficacy scores were also positively correlated with maternal self-efficacy scores (ρ=0.30, p=.01). However, the results of Tobit regression analyses indicated that paternal self-efficacy scores did not moderate the relationship between maternal self-efficacy scores and exclusive breastfeeding duration. Only maternal self-efficacy scores were significantly associated with duration of exclusive breastfeeding (B=.16, p<.01).
KEY CONCLUSIONS
This is the first Thai study to assess the relationship between fathers' breastfeeding support self-efficacy and exclusive breastfeeding duration. The results increase our understanding of paternal factors that impact exclusive breastfeeding duration. Although paternal self-efficacy did not moderate the effects of maternal self-efficacy on exclusive breastfeeding duration in this study, paternal self-efficacy positively related to maternal self-efficacy and breastfeeding duration.
IMPLICATION FOR PRACTICE
Paternal breastfeeding support self-efficacy should be promoted in co-parenting breastfeeding interventions both antenatal care clinics and postpartum units to promote exclusive breastfeeding and increase Thailand's overall exclusive breastfeeding rate. | 10.1016/j.midw.2022.103261 |
pubmed_14_1568 | Novel agarose-dextran hydrogels were synthesized and their suitability as experimental models of glomerular basement membrane was examined by measuring their Darcy (hydraulic) permeabilities (kappa). Immobilization of large dextran molecules in agarose was achieved by electron beam irradiation. Composite gels were made with agarose volume fractions (phi(a)) of 0.04 or 0.08 and dextran volume fractions (phi(d)) ranging from 0 to 0.02 (fiber volume/gel volume), using either of two dextran molecular weights (500 or 2000). At either agarose concentration and for either size of dextran, kappa decreased markedly as the amount of dextran was increased. Statistically significant deviations from the value of kappa for pure agarose were obtained for remarkably small volume fractions of dextran: phi(d) > or = 0.0003 for phi(a) = 0.04 and phi(d) > or = 0.001 for phi(a) = 0.08. The Darcy permeabilities were much more sensitive to phi(d) than to phi(a), and were as much as 26 times smaller than those of pure agarose. Although phi(d) was an important variable, dextran molecular weight was not. The effects of dextran addition on kappa were described fairly well using simple structural idealizations. At high agarose concentrations, the dextran chains behaved as fine fibers interspersed among coarse agarose fibrils, whereas, at low concentrations, the dextran molecules began to resemble spherical obstacles embedded in agarose gels. The ability to achieve physiologically relevant Darcy permeabilities with these materials (as low as 1.6 nm2) makes them an attractive experimental model for glomerular basement membrane and possibly other extracellular matrices. | 10.1016/S0006-3495(02)75555-0 |
pubmed_738_9793 | The COVID-19 outbreak was declared a public health emergency of international concern by the World Health Organization on January 30, 2020. Since then, the virus has spread to affect more countries worldwide. During this period, our nuclear medicine department at Singapore General Hospital segregated our staff and patients by time, by space, or both, to minimize contact and prevent spread of the virus. Necessary changes to our clinical practices and stricter infection control measures were also enforced. We share our personal experience in managing a nuclear medicine department during this epidemic. | 10.2967/jnmt.120.244855 |
pubmed_5_16317 | BACKGROUND
The purpose of Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT) was to improve outcomes for seriously ill hospitalized adults by improving information and decision-making. The SUPPORT intervention has been characterized only briefly in previous publications.
OBJECTIVE
To characterize the intervention in SUPPORT and its implementation.
DESIGN
Reports derived from training and administrative materials, quantitative descriptions of implementation activities, and qualitative analysis of narrative reports and focus group participation by the intervention nurses.
SETTING AND PATIENTS
SUPPORT enrolled 2652 patients in the intervention arm and 2152 in the control arm of a block-randomized trial of enhanced information, counseling, and support. The patients were hospitalized with one of nine serious illnesses in one of five US teaching hospitals between 1992 and 1994.
MEASUREMENTS
(1) Reports on training and supervisory materials; (2) Rates of intervention component completion from contact logs and reports completed by the intervention nurses; and (3) grounded theory analysis of patient narratives, overview questionnaires, and focus group transcripts from the intervention nurses.
RESULTS
Prognostic reports were delivered on time to the caregiving team in 83% of cases on Day 3. Reports of surrogate interviews of patient preferences and understanding were delivered on time to the caregiving team in 72% of first week cases. Patients' own reports of preferences were unavailable for 56% of cases in the first week. Overall, 39% of the rest of the patients had their interview information delivered on time to the caregiving team. The SUPPORT intervention nurses averaged 8.5 contacts with patients, 7.6 with surrogates, 3.5 with physicians, and 11.7 with other staff. The intervention nurses felt that they were fully involved in 81% of cases and had a limited role in another 14%. The major issues for patients were: understanding their situation, communication and decision-making, advance planning, do not resuscitate orders, and general support, including support for loss and grieving. The narrative sources showed that the nurses were enthusiastic, dedicated, and strong in their support of the study objectives. They identified various barriers to effectiveness and voiced doubt that the analytic targets would show an effect from the intervention.
CONCLUSIONS
The SUPPORT intervention was implemented vigorously and completely. | pubmed_5_16317 |
pubmed_713_6114 | Phoma black stem and leaf spot disease of annual Medicago spp., caused by Phoma medicaginis, not only can devastate forage and seed yield but can reduce herbage quality by inducing production of phytoestrogens (particularly coumestrol and 4'-O-methylcoumestrol), which can also reduce the ovulation rates of animals grazing infected forage. We determined the consequent phytoestrogen levels on three different annual Medicago species/cultivars (Medicago truncatula cultivar Cyprus, Medicago polymorpha var. brevispina cultivar Serena, and Medicago murex cultivar Zodiac) after inoculation with 35 isolates of P. medicaginis. Across the isolate × cultivar combinations, leaf disease incidence, petiole/stem disease incidence, leaf disease severity, petiole disease severity, and leaf yellowing severity ranged up to 100, 89.4, 100, 58.1, and 61.2%, respectively. Cultivars Cyprus and Serena were the most susceptible and cultivar Zodiac was the most resistant to P. medicaginis. Isolates WAC3653, WAC3658, and WAC4252 produced the most severe disease. Levels of phytoestrogens in stems ranged from 25 to 1,995 mg/kg for coumestrol and from 0 to 418 mg/kg for 4'-O-methylcoumestrol. There was a significant positive relationship of disease incidence and severity parameters with both coumestrol and 4'-O-methylcoumestrol contents, as noted across individual cultivars and across the three cultivars overall, where r = 0.39 and 0.37 for coumestrol and 4'-O-methylcoumestrol, respectively (P < 0.05). Although cultivar Serena was most susceptible to P. medicaginis and produced the highest levels of phytoestrogens in the presence of P. medicaginis, cultivar Zodiac contained the highest levels of phytoestrogens in comparison with other cultivars in the absence of P. medicaginis. There was a 15-fold increase in coumestrol in cultivar Serena but only a 7-fold increase in cultivar Zodiac from infection of P. medicaginis. The study highlights that the intrinsic ability of a particular cultivar to produce phytoestrogens in the absence of the pathogen, and its comparative ability to produce phytoestrogens in the presence of the P. medicaginis, are both important and highly relevant to developing new annual Medicago spp. cultivars that offer improved disease resistance and better animal reproductive outcomes. | 10.1094/PDIS-03-21-0606-RE |
pubmed_509_25709 | To screen candidate methylation markers for early detection of breast cancer and to explore the relationship between methylation and gene expression, we performed methylated-CpG island recovery assay (MIRA) combined with CpG island array on 61982 CpG sites across 4162 genes in 10 cancerous and 10 non-cancerous breast tissues. Direct bisulfite sequencing and combined bisulfite restriction analysis (COBRA) were carried out in independent cancerous and non-cancerous samples. Gene expression was analyzed by microarrays and validated using RT-PCR. We detected 70 significantly hypermethylated genes in breast cancer tissues, including many novel hypermethylated genes such as ITGA4, NFIX, OTX2 and FGF12. Direct bisulfite sequencing showed widespread methylation occurring in intragenic regions of the WT1, PAX6 and ITGA4 genes and in the promoter region of the OTX2 gene in breast cancer tissues. COBRA assay confirmed that the WT1, OTX2 and PAX6 genes were hypermethylated in breast cancer tissues. Clustering analysis of the gene expression of 70 significantly hypermethylated genes revealed that most hypermethylated genes in breast cancer were not expressed in breast tissues. RT-PCR assay confirmed that WT1 and PITX2 were only weakly expressed in the breast cancer tissues and were not expressed in most non-cancerous breast tissues. OTX2 and PAX6 were not expressed in either breast cancer or non-cancerous tissues. In conclusion, these results will expand our knowledge of hypermethylated genes and methylation sites for early detection of breast cancer and deepen our understanding of the relationship between methylation and gene expression. The MIRA approach can screen candidate methylated genes for further clinical validation more effectively than gene expression microarray-based strategy. | 10.3892/ijo.2012.1464 |
pubmed_1011_5166 | Specific receptors for iodine-labelled human prolactin ([125I]hPrl) are present in membrane preparations of the rat ventral prostate. The binding is saturable with an apparent association constant (Ka) of 2.2 X 10(9) M-1 and a binding capacity of about 1 pmol/100mg prostatic tissue. The binding of [125I]hPrl is inhibited by hPrl, ovine Prl (otprl) and human growth hormone, but not by ovine FSH or LH. Serum from rats having Prl-producing pituitary tumors caused a displacement of the [125I]hPrl from the receptors, and the displacement curve was parallel with that of the hPrl standard. Treatment of immature rats with varying doses of dihydrotestosterone propionate (10-5000 microng) causes a dose-dependent stimulation of Prl receptors calculated both as binding sites per mg of membrane protein and as binding sites per prostate. Androgen stimulation of prostatic Prl receptors increases the tissue sensitivity for circulating Prl and may be one reason for the known increases in endogenous cAMP levels in prostatic tissue after androgen treatment in vivo. | 10.1016/0303-7207(77)90070-3 |
pubmed_836_16431 | A retrospective study was performed to (1) characterize the clinical and histologic features of those with nonalcoholic fatty liver disease (NAFLD) and normal alanine aminotransferase (ALT) values, (2) compare the spectrum of NAFLD associated with normal versus elevated ALT levels, and (3) determine whether there were differences in the clinical or histologic spectrum of NAFLD between those with a low normal versus high normal ALT value. A total of 51 subjects with NAFLD and normal ALT were identified and compared with 50 consecutive subjects with NAFLD and elevated ALT. The major indications for liver biopsy in those with normal ALT were unexplained hepatomegaly (n = 21) and evaluation as a potential donor for living donor liver transplantation (n = 16). The 2 groups were comparable with respect to age, gender distribution, and ethnicity. Approximately 80% of cases in both groups had at least 1 feature of the metabolic syndrome, the major risk factor for NAFLD. The 2 groups were also comparable with respect to the grade of the individual histologic parameters of NAFLD. A total of 12 subjects with normal ALT levels had bridging fibrosis, whereas 6 had cirrhosis. Diabetes was the only factor independently associated with an increased risk of advanced fibrosis (bridging fibrosis or cirrhosis) by multivariate analysis (relative risk: 2.3, P <.01). The mean steatosis (1.6 vs. 2.16, P <.04) and perisinusoidal fibrosis scores (0.35 vs. 0.9, P <.049) were lower in those with low normal (<30 IU/L) ALT versus high normal ALT. However, the prevalence of advanced fibrosis was similar (5 of 15 vs. 13 of 36, respectively). In conclusion, (1) the entire histologic spectrum of NAFLD can be seen in individuals with normal ALT values, (2) the histologic spectrum in these individuals is not significantly different from those with elevated ALT levels, and (3) a low normal ALT value does not guarantee freedom from underlying steatohepatitis with advanced fibrosis. | 10.1053/jhep.2003.50229 |
pubmed_707_22138 | BACKGROUND AND AIMS
Innate lymphoid cells (ILCs) are tissue-resident lymphocytes that play critical roles in cytokine-mediated regulation of homeostasis and inflammation. However, relationships between their immune phenotypic characteristics and HCC remain largely unexplored.
APPROACH AND RESULTS
We performed single-cell RNA sequencing analysis on sorted hepatic ILC cells from human patients with HCC and validated using flow cytometry, multiplex immunofluorescence staining, and functional experiments. Moreover, we applied selection strategies to enrich ILC populations in HCC samples to investigate the effects of B cells on the immune reaction of inducible T cell costimulator (ICOS)+ ILC2 cells. Dysregulation of ILCs was manifested by the changes in cell numbers or subset proportions in HCC. Seven subsets of 3433 ILCs were identified with unique properties, of which ICOS+ ILC2a were preferentially enriched in HCC and correlated with poor prognosis. Mechanistically, we report that B cells, particularly resting naïve B cells, have a previously unrecognized function that is involved in inflammatory differentiation of ILC2 cells. B cell-derived ICOSL signaling was responsible for exacerbating inflammation through the increased production of IL-13 in ICOS+ ILC2a cells. Heat shock protein 70 (HSP70) genes Heat Shock Protein Family A Member 1A (HSPA1A) and Heat Shock Protein Family A Member 1B (HSPA1B) were highly expressed in ILC2s in late-stage HCC, and targeting to ICOS and its downstream effector HSP70 in ILC2s suppressed tumor growth and remodeled the immunosuppressive tumor microenvironment.
CONCLUSIONS
This in-depth understanding sheds light on B cell-driven innate type 2 inflammation and provides a potential strategy for HCC immunotherapy. | 10.1002/hep.32444 |
pubmed_48_1449 | OBJECTIVE The authors performed a study to identify clinical characteristics of pediatric patients diagnosed with Chiari I malformation and scoliosis associated with a need for spinal fusion after posterior fossa decompression when managing the scoliotic curve. METHODS The authors conducted a multicenter retrospective review of 44 patients, aged 18 years or younger, diagnosed with Chiari I malformation and scoliosis who underwent posterior fossa decompression from 2000 to 2010. The outcome of interest was the need for spinal fusion after decompression. RESULTS Overall, 18 patients (40%) underwent posterior fossa decompression alone, and 26 patients (60%) required a spinal fusion after the decompression. The mean Cobb angle at presentation and the proportion of patients with curves > 35° differed between the decompression-only and fusion cohorts (30.7° ± 11.8° vs 52.1° ± 26.3°, p = 0.002; 5 of 18 vs 17 of 26, p = 0.031). An odds ratio of 1.0625 favoring a need for fusion was established for each 1° of increase in Cobb angle (p = 0.012, OR 1.0625, 95% CI 1.0135-1.1138). Among the 14 patients older than 10 years of age with a primary Cobb angle exceeding 35°, 13 (93%) ultimately required fusion. Patients with at least 1 year of follow-up whose curves progressed more 10° after decompression were younger than those without curve progression (6.1 ± 3.0 years vs 13.7 ± 3.2 years, p = 0.001, Mann-Whitney U-test). Left apical thoracic curves constituted a higher proportion of curves in the decompression-only group (8 of 16 vs 1 of 21, p = 0.002). CONCLUSIONS The need for fusion after posterior fossa decompression reflected the curve severity at clinical presentation. Patients presenting with curves measuring > 35°, as well as those greater than 10 years of age, may be at greater risk for requiring fusion after posterior fossa decompression, while patients less than 10 years of age may require routine monitoring for curve progression. Left apical thoracic curves may have a better response to Chiari malformation decompression. | 10.3171/2016.5.PEDS16180 |
pubmed_926_12901 | According to the literature, sigmoid volvulus typically develops in patients of an older age with co-morbidities such as a psychiatric illness or a bed-bound chronic illness. Recent reports suggest that it should also be considered in young individuals without any preceding medical history. Abdominal roentgenography is a cheap and effective diagnostic modality that can avoid a delay in diagnosis. The treatment of colonic volvulus remains controversial and relies upon the procedure selected and the most appropriate therapeutic approach in terms of the clinical status of the patient, the location of the problem, the suspected existence or identification of peritonitis, bowel viability, and the expertise of the surgical team. Presented here are four cases of young male patients with sigmoid volvulus. All of the patients were diagnosed radiologically prior to surgical intervention. Two of the patients initially underwent an endoscopic procedure that succeeded in one and that failed in the other. Three of the patients underwent a laparotomy. | 10.5582/irdr.2017.01033 |
pubmed_700_10780 | The muscle contraction of the anterior tibial muscle was investigated by measurements of electrically stimulated and computer-analyzed muscle twitches in 18 unselected patients with primary hyperparathyroidism (HPT) and in 20 healthy control persons. The HPT patients had a lower muscle twitch tension (TT) at single stimulation, compared with the control group [76 +/- 24 N (SD) and 99 +/- 33 N respectively, P less than 0.05]. At high-frequency stimulation the difference in muscle force increased, and at 20 Hz stimulation the force in the HPT patients was 73% of that in the controls (P less than 0.01). There were no differences between the HPT patients and the control persons in neither contraction time nor half relaxation time at single muscle twitch nor in twitch potentiation after 20 and 90 seconds maximal voluntary contraction. The results indicate that patients with primary HPT have an impaired muscle function of probable importance for their symptoms of weakness and generalized fatigue. | 10.1002/mus.880120202 |
pubmed_997_3707 | Biosynthetic gene clusters (BGCs) in microbial genomes encode bioactive secondary metabolites (SMs), which can play important roles in microbe-microbe and host-microbe interactions. Given the biological significance of SMs and the current profound interest in the metabolic functions of microbiomes, the unbiased identification of BGCs from high-throughput metagenomic data could offer novel insights into the complex chemical ecology of microbial communities. Currently available tools for predicting BGCs from shotgun metagenomes have several limitations, including the need for computationally demanding read assembly, predicting a narrow breadth of BGC classes, and not providing the SM product. To overcome these limitations, we developed taxonomy-guided identification of biosynthetic gene clusters (TaxiBGC), a command-line tool for predicting experimentally characterized BGCs (and inferring their known SMs) in metagenomes by first pinpointing the microbial species likely to harbor them. We benchmarked TaxiBGC on various simulated metagenomes, showing that our taxonomy-guided approach could predict BGCs with much-improved performance (mean F1 score, 0.56; mean PPV score, 0.80) compared with directly identifying BGCs by mapping sequencing reads onto the BGC genes (mean F1 score, 0.49; mean PPV score, 0.41). Next, by applying TaxiBGC on 2,650 metagenomes from the Human Microbiome Project and various case-control gut microbiome studies, we were able to associate BGCs (and their SMs) with different human body sites and with multiple diseases, including Crohn's disease and liver cirrhosis. In all, TaxiBGC provides an in silico platform to predict experimentally characterized BGCs and their SM production potential in metagenomic data while demonstrating important advantages over existing techniques. IMPORTANCE Currently available bioinformatics tools to identify BGCs from metagenomic sequencing data are limited in their predictive capability or ease of use to even computationally oriented researchers. We present an automated computational pipeline called TaxiBGC, which predicts experimentally characterized BGCs (and infers their known SMs) in shotgun metagenomes by first considering the microbial species source. Through rigorous benchmarking techniques on simulated metagenomes, we show that TaxiBGC provides a significant advantage over existing methods. When demonstrating TaxiBGC on thousands of human microbiome samples, we associate BGCs encoding bacteriocins with different human body sites and diseases, thereby elucidating a possible novel role of this antibiotic class in maintaining the stability of microbial ecosystems throughout the human body. Furthermore, we report for the first time gut microbial BGC associations shared among multiple pathologies. Ultimately, we expect our tool to facilitate future investigations into the chemical ecology of microbial communities across diverse niches and pathologies. | 10.1128/msystems.00925-22 |
pubmed_564_2844 | The potential of anatomic imaging to improve the quantitative accuracy of functional brain imaging through refined regional definition is widely accepted. However, there are little data addressing the impact of approach to regional localization on quantitation of metabolic images in the absence of gross structural pathology. We compared MRI-based versus PET-based approaches to the analysis of PET 18F-fluorodeoxyglucose (FDG) images using a standard adjustable template based on simple geometric regions. For the MRI-based approach, templates and individual regions were adjusted to each individual's anatomy, whereas the PET-based definition involved only global proportional adjustment of the standard templates. Metabolic rates for glucose and volume-to-whole brain ratios were determined by two operators for 78 volumes of interest in five subjects. Pairwise correlations indicated high interoperator agreement for each approach and high intraoperator agreement for MRI-based versus PET-based metabolic values. The stability of the metabolic rates and ratios among operators and analysis approaches was supported by low coefficients of variation across measurements and small average differences in paired comparisons. Thus, within the current spatial resolution of PET imaging, quantitation of metabolic images is relatively robust to image analysis approach in the absence of gross structural abnormality. To take advantage of the greater quantitative accuracy promised by high-resolution anatomic and functional imaging, more refined delineation of anatomic images will be necessary. | pubmed_564_2844 |
pubmed_63_876 | SYNOPSIS
There is irrefutable evidence of an association between mechanical neck pain (MNP) and dysfunction of the muscles of the cervical spine. A myriad of impairments have been demonstrated that include changes in the physical structure (cross-sectional area, fatty infiltration, fiber type), as well as changes in behavior (timing and activation level), of the cervical muscles. Such changes suggest an impaired capacity of the cervical muscles to generate, sustain, and maintain precision of the required levels of torque needed for optimal function. In the context of physical support, these changes potentially have deleterious consequences for the cervical region, which relies heavily on its muscles for mechanical stability. While interventions focused on the retraining of cervical muscle function have shown favorable responses in alleviating MNP, the development of best practice strategies for the assessment and management of cervical muscle dysfunction is still a work in progress. One obstacle in researching the efficacy of cervical muscle training is that, as yet, we do not possess the capacity to optimally measure and classify those patients most likely to respond to different methods of training that would enrich clinical practice. While gains in this area are emerging, the ability of a clinician to best identify the need and implement the most appropriate method of training cervical muscle function is still largely dependent on a comprehensive examination of the patient that considers all aspects of the patient's disorder and functional requirements.
LEVEL OF EVIDENCE
Level 5. | 10.2519/jospt.2009.2872 |
pubmed_666_7204 | Proteins extracted from microalgae for food, personal care products and cosmetics must be of high purity, requiring solvent-free extraction techniques despite their generally considerably lower protein yield and higher energy consumption. Here, three such approaches for green extraction of proteins from Chlorella vulgaris were evaluated: ultrasound, freeze-thawing, and electroporation; chemical lysis was used as positive control (maximal achievable extraction), and no extraction treatment as negative control. Compared to chemical lysis, electroporation yielded the highest fraction of extracted protein mass in the supernatant (≤27%), ultrasound ≤24%, and freeze-thawing ≤15%. After a growth lag of several days, electroporated groups of algal cells started to exhibit growth dynamics similar to the negative control group, while no growth regeneration was detected in groups exposed to ultrasound, freeze-thawing, or chemical lysis. For electroporation as the most efficient and the only non-destructive among the considered solvent-free protein extraction techniques, simultaneous extraction of intracellular algal lipids into supernatant was then investigated by HPLC, proving relatively low-yield (≤7% of the total algal lipid mass), yet feasible for glycerides (tri-, di-, and mono-) as well as other fatty acid derivatives. Our results show that electroporation, though lower in extraction yields than chemical lysis or mechanical disintegration, is in contrast to them a technique for largely debris-free extraction of proteins from microalgae, with no need for prior concentration or drying, with feasible growth regeneration, and with potential for simultaneous extraction of intracellular algal lipids into the supernatant. | 10.3389/fbioe.2020.00443 |
pubmed_302_19942 | Long-term pain relief and improved function in patients with failed or infected hip replacement, or, occasionally for patients with impending surgical failure, are the goals of total hip revision arthroplasty. Cement techniques for femoral and reconstructions in patients needing total hip revision are discussed in this article. Advantages of cemented technique include the ability to incorporate antibiotics into the cement during reimplantation following periprosthetic infection. Cemented technique is also preferable over cementless techniques when there is extensive diaphyseal bone loss, which precludes predictable biologic fixation. Cement-within-cement technique is indicated for well-fixed cemented femoral components that require revision for instability, improved acetabular exposure, equalization of leg lengths, or damage to a monoblock femoral head. | pubmed_302_19942 |
pubmed_963_17373 | Abnormal phosphorylation has been proposed to be involved in the pathogenesis of affective disorders. The present study investigated basal and cAMP-stimulated endogenous protein phosphorylation in human post-mortem brain tissue from bipolar and schizophrenic patients. Furthermore, basal kinase activity and stimulated protein kinase A activity were measured. The frontal and occipital cortex were analysed. Using [gamma-32P]ATP as phosphate donor, basal and cAMP-stimulated phosphorylation of endogenous proteins was measured in the absence or presence of 8-Br-cAMP, respectively. The proteins were separated on SDS-gels and the radioactivity in the individual bands was measured. We observed a significant reduction of 32P incorporation in three protein substrates (15, 16 and 21 kD) in frontal cortex of bipolar patients. However, there were no differences in the PKA activity between any of the groups. The present study demonstrates abnormal phosphorylation of specific proteins in brain tissue obtained from bipolar patients in comparison to schizophrenics and controls. | 10.1007/s007020070091 |
pubmed_690_6046 | Corneal anesthesia or hypesthesia can complicate refractive surgical procedures such as epikeratophakia and radial keratotomy. An esthesiometer was used to measure the corneal sensitivity in unoperated-on corneas and fellow corneas after excimer laser photorefractive keratectomy. Decrease in corneal sensitivity was noted within six postoperative weeks, with mean sensitivity being 75.2% +/- 13.3% of normal. Within the first three postoperative months, the patients operated on for correction of compound astigmatism recovered 95.7% +/- 5.3% of the corneal sensitivity, whereas the patients operated on for correction of severe myopia recovered 86.2% +/- 11.2% (P = .07). None of the patients had delayed epithelial healing or recurrent corneal erosions during the time of decreased corneal sensitivity. In otherwise normal myopic eyes, photorefractive keratectomy measurably reduced corneal sensitivity for several postoperative weeks. | 10.1016/s0002-9394(14)77412-4 |
pubmed_747_5275 | Sprague-Dawley rats and AKR/J mice were exposed to 300 ppm benzene vapor for 6 h/d, 5 d/wk, for life. Rats exhibited lymphocytopenia, mild anemia, and moderately decreased survival. Mice showed severe lymphocytopenia and anemia accompanied by granulocytosis and reticulocytosis. Treated mice also showed significantly decreased survival and weight gain. No indications of a leukemic or preleukemic response were observed in either species. | 10.1080/15287397809529683 |
pubmed_1072_19668 | BACKGROUND
To report the use of scleral lens (ScCL) to improve vision in patients having keratoconus who had intracorneal ring segment (ICRS) surgery.
METHODS
Two eyes of two keratoconus patients fitted with ScCL (PROSE - prosthetic replacement of the ocular surface ecosystem, USA) after having undergone ICRS surgery are reported as noncomparative interventional case series. The ICRS implanted were INTACs and kerarings. Indications, visual acuity with ScCL, complications and follow-up are reported.
RESULTS
Case 1 underwent ScCL trial as he was referred for keratoplasty for being contact lens intolerant after ICRS surgery. Case 2 was intolerant to both corneal rigid gas permeable (RGP) lens and soft contact lens (SCL). 18.5 and 18mm diameter ScCLs were dispensed to Case 1 and 2 respectively. The ScCLs had adequate corneal clearance with no corneal touch. There was no staining of the cornea or vascularization with the lens use. Case 1 complained of double images during trial with different Front surface eccentricity (FSE). A ScCL that did not cause diplopia was ordered. At four months of lens wear, the patient had diplopia with ScCL, which cleared when second lens with changed FSE was dispensed. Case 2 used SCL for five years before ScCL was fitted. He used the same ScCLs for five years. ScCL use resulted in improved comfort and visual acuity of 20/20. No complications were noted.
CONCLUSIONS
ScCL may be tried in patients who have ICRS and are intolerant to corneal RGP or SCL and before subjecting such patients to keratoplasty. | 10.1016/j.clae.2017.10.013 |
pubmed_718_18746 | Enteroaggregative Escherichia coli (EAggEC) has been found to be associated with acute and persistent diarrhoea in children in developing countries. Its clinical significance in developed countries has not been examined in much detail. In a survey of faecal samples from children with diarrhoea presenting to a children's hospital in East London between August and December 1988, EAggEC strains were isolated in 8 of 297 (2.7%) consecutive stool samples collected from 289 children and in 5 of 34 typed E. coli isolates during 1988. Of the 13 children found to be excreting EAggEC, 8 had acute diarrhoea and 5 had chronic diarrhoea of more than 14 days' duration; 5 children had mixed infections. Compared to other organisms found during the same period, EAggEC were isolated as frequently as many other better-known pathogens such as enteropathogenic E. coli, Campylobacter, Salmonella, Shigella, Giardia lamblia, and Cryptosporidium. We conclude that EAggEC may be an important pathogen in developed countries. | pubmed_718_18746 |
pubmed_100_4986 | We investigated the association of undiagnosed diabetes, previously known diabetes and prediabetes (WHO 1999 classification) with all-cause and cause-specific mortality in an older German population. Previous study results for mortality in patients with very low levels of HbA1c, fasting plasma glucose (FPG), and 2-h plasma glucose (2hPG) are still inconclusive. Thus we have extended the analyses to continuous measures of glycemia. A total of 1,466 subjects aged 55-74 years from the population-based KORA survey S4 (conducted from 1999 to 2001) were included in our observational mortality study (152 subjects with previously known diabetes, and 1,314 further subjects who underwent oral glucose tolerance tests). Mortality was followed up for a maximum of 10.0 years (median follow-up 8.8 years). A total of 180 (12.3%) of the 1,466 subjects have died during the follow-up period. The age- and sex-adjusted hazard ratios for all-cause mortality were 2.6 (95%CI, 1.7-3.8) for known diabetes, 2.8 (95%CI, 1.7-4.4) for undiagnosed diabetes, and 1.1 (95%CI, 0.8-1.7) for prediabetes [reference: normal glucose tolerance (NGT)]. After multivariable adjustment, undiagnosed diabetes was associated with 3.0-fold increased cancer mortality, 1.1-fold increased cardiovascular mortality, and 4.7-fold increased non-cancer, non-cardiovascular mortality compared with NGT. For HbA1c, FPG, and 2hPG, J-shaped associations with all-cause mortality were observed. Undiagnosed diabetes is associated with increased all-cause, cancer, and non-cancer non-cardiovascular mortality, but not with cardiovascular mortality in this older population. All-cause mortality in undiagnosed diabetes is similar to that in previously known diabetes but much higher than mortality in prediabetes and NGT. | 10.1007/s10654-011-9609-y |
pubmed_997_275 | Chemokines are key instigators of inflammatory and immune responses. Viruses can suppress these responses by secreting proteins that interfere with chemokine action. These proteins bind to chemokines and block the host's ability to recruit immune cells to sites of infection, thus facilitating virus replication and spread. When produced recombinantly, chemokine binding proteins provide a formidable resource to deploy against human disease. Here, we describe an enzyme-linked immunosorbent inhibition assay and a chemotaxis inhibition assay that are employed to assess the chemokine binding strength and anti-chemotactic activity of viral proteins. These assays are quick and reproducible, and are thus ideal for screening putative or modified chemokine binding proteins as the first step in their development as therapeutics. | 10.1007/978-1-0716-2835-5_16 |
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