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pubmed_748_1302 | We describe in this paper the development of a one-step sandwich assay for the highly sensitive and fast detection of human matrix metalloproteinase (MMP)-2 (EC 3.4.24.24), using surface plasmon resonance (SPR). For the assay, two ligands were selected: monoclonal anti-MMP-2 antibody Ab-2 and the tissue inhibitor of metalloproteinases (TIMP)-2. They were chosen on the basis of (1) their affinities to MMP-2, (2) the efficiency of immobilization to the sensor chip, (3) the efficiency of adsorption to colloidal gold, and (4) the stability of these protein-coated gold particles. The assay included mixing of MMP-2 with antibody Ab-2 adsorbed to colloidal gold with a diameter of about 20nm and injection into the flowcell of the SPR instrument containing immobilized TIMP-2. By using colloidal gold particles an amplification factor of 114 and a detection limit of 0.5pM for MMP-2 were obtained. The precision of the assay was high even at low analyte concentrations, the standard deviation being 8.3% for five determinations of 1pM MMP-2. No significant binding was observed with the structurally related MMP-9. The assay is far more sensitive and faster than commonly used methods for MMP-2 detection. As TIMP-bound MMP-2 is not detected by this method, the assay can be applied for measuring free MMP-2, reflecting the imbalance of free and inhibitor-bound enzyme in various pathological situations. | 10.1016/j.ab.2004.05.047 |
pubmed_692_21960 | Drug addiction is characterized by compulsive drug-taking behaviors and a high propensity to relapse following drug cessation. Drug craving and seeking can increase during a period of abstinence, but this phenomenon is not observed in drug-induced reinstatement models. To investigate the effect of withdrawal on cocaine relapse, rats were exposed to extended-access cocaine self-administration and subjected to either 1 or 30 d of withdrawal. When tested during 12 h unlimited access to cocaine (binge), the duration of the withdrawal did not influence cocaine intake. However, using a histamine punishment procedure that greatly suppresses drug-taking behavior, we demonstrate that longer periods of abstinence from cocaine induce a greater persistence in responding for drug in the face of negative consequences. | 10.1038/srep06876 |
pubmed_317_17828 | A variety of ion channels has been discovered in lymphocytes. RT-PCR and real-time PCR analysis revealed that ALL (acute lymphocytic leukemia) cell lines and human peripheral blood mononuclear cells mainly expressed TTX (tetrodotoxin)-sensitive voltage-gated sodium channels (VGSCs). Expression of VGSC protein was confirmed by western blots and Immunofluorescence. Whole-cell patch-clamp recordings showed that a sub-population (20%) of MOLT-4 cells expressed functional VGSCs, which were TTX-sensitive. Importantly, 2 μM TTX decreased the invasion of Jurkat and MOLT-4 cells ∼90%. These results indicate that the activity of VGSCs could represent a novel mechanism potentiating the invasive capacity of these cells. | pubmed_317_17828 |
pubmed_529_7844 | A new dimeric acylphloroglucinol, denudatin A (1), was isolated from the flowering aerials parts of Hypericum denudatum, along with the known phloroglucinols selancin A (2), hyperbrasilol A (3), uliginosin B (4), and isouliginosin B (5). The structure of 1 was elucidated using 1D, 2D NMR, and MS experiments, and by comparison with previously reported data for Hypericum dimeric acylphloroglucinols. Denudatin A (1) and selancin A (2) were administered orally to mice displaying antinociceptive activity in the hot plate test. The compounds did not induce motor impairment in the rotarod apparatus. | 10.1055/s-0043-109567 |
pubmed_659_22880 | Objectives
The aim of this study was to evaluate the most ideal inflammatory markers for treatment response and to determine a cutoff value that could predict response to treatment for culture negative neutrocytic ascite (CNNA) patients.
Methods
This is a retrospective cross-sectional case-controlled study. Patients with CNNA were evaluated by taking ascites fluid sampling at the beginning and on the 5th day of treatment. Neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and neutrophil-to-monocyte ratio were calculated.
Results
Of the 123 cases with cirrhotic ascites disease, 59 were CCNA and 64 were the control group without ascite-fluid infection. There were statistically significant differences for blood monocyte count, NLR (p<0.01), LMR, and C-reactive protein (CRP) (p<0.001) between two groups. Patients in the CNNA group were compared before and after treatment among themselves for the treatment response. There was statistically significant difference in mean platelet volume, monocyte, LMR, and CRP (p<0.05) between two groups. After receiver operator characteristics curve analysis, the best cutoff value for monocyte was <0.64 × 103/μL (sensitivity 49.2%, specificity 74.6%, positive predictive value [PPV] 65.9%, and negative predictive value [NPV] 59.5%) (p<0.01), for LMR was ≥1.7 (sensitivity 76.3%, specificity 78%, PPV 77.6%, and NPV 76.7%), and for CRP was ≤18 mg/L (sensitivity 91.5% specificity 57.6%, PPV 68.4%, and NPV 87.2%) (p<0.001). When LMR and CRP were used together, sensitivity (86.5%), specificity (83.1%), PPV (83.6%), and NPV (86%) were found to be statistically significantly higher (p<0.001).
Conclusion
Our results showed that in cirrhotic patients with CNNA, combined LMR + CRP can be used as a novel, low cost and non-invasive test to predict treatment response. | 10.14744/SEMB.2021.58219 |
pubmed_812_11407 | We describe the clinical and radiological results of 38 total hip replacements (THR) using the JRI Furlong hydroxyapatite-ceramic (HAC)-coated femoral component in patients younger than 50 years. The mean age at the time of operation was 42 years (22 to 49) and the mean length of follow-up was ten years (63 to 170 months). All patients receiving a Furlong HAC THR were entered into the study regardless of the primary pathology including patients who had undergone previous hip surgery. The mean Harris hip score improved from 44 before operation to 92 at the last post-operative review. After 12 years the cumulative surivival for the stem was 100% (95% confidence interval 89 to 100). No femoral component was revised. Our results show that the Furlong HAC implant gives excellent long-term results in young patients with high demands. | 10.1302/0301-620x.86b8.14928 |
pubmed_314_19508 | New macrocyclic binuclear nickel(ii) complexes have been synthesized by using the bicompartmental mononuclear complex [NiL] [3,30-((1E,7E)-3,6-dioxa-2,7-diazaocta-1,7-diene-1,8-diyl)bis(3-formyl-5-methyl-2-diolato)nickel(II)] with various diamines like 1,2-bis(aminooxy)ethane (L(1)), 1,2-diamino ethane (L(2)), 1,3-diamino propane (L(3)), 1,4-diamino butane (L(4)), 1,2-diamino benzene (L(5)), and 1,8-diamino naphthalene (L(6)). The complexes were characterized by elemental analysis and spectroscopic methods. The molecular structures of the symmetrical binuclear complex [Ni(2)L(1)(H(2)O)(4)](ClO(4))(2) (1) and unsymmetrical binuclear complex [Ni(2)L(3)(H(2)O)(4)](ClO(4))(2).(H(2)O)(4) (3) were determined by single-crystal X-ray diffraction. The geometry around both the nickel(II) ions in each molecule is a slightly distorted octahedral. The distance between the Ni...Ni centers for complex 1 is 3.039 A and for complex 3 is 3.059 A. The influence of the coordination geometry and the ring size of the binucleating ligands on the electronic, redox, phosphate hydrolysis, DNA binding and cleavage properties have been studied. Electrochemical studies of the complexes show two quasi-reversible one electron reduction processes between -0.49 to -1.69 V. The reduction potential of the binuclear Ni(II) complexes shifts towards anodically upon increasing the macrocyclic ring size. The observed first order rate constant values for the hydrolysis of 4-nitrophenyl phosphate reaction are in the range from 8.69 x 10(-3) to 1.85 x 10(-2) s(-1). The complexes show good binding propensity to calf thymus DNA giving binding constant values in the range from 1.4 x 10(4) to 17.5 x 10(4) M(-1). The absorption, fluorescence and CD spectral data suggests that the complexes are strongly interacting with DNA. These complexes display hydrolytic cleavage of supercoiled pBR322DNA in the presence of H(2)O(2) at pH 7.2 and 37 degrees C. The hydrolytic cleavage of DNA by the complexes is supported by the evidence from free radical quenching and T4 ligase ligation. The pseudo-Michaelis-Menten kinetic parameters k(cat) = 1.27 +/- 0.4 h(-1) and K(M) = 7.7 x 10(-2) M for naphthalene diimine containing macrocyclic binuclear nickel(II) complex, (6) were obtained. | 10.1039/b923078e |
pubmed_496_16915 | A multidiffusion-tensor model (MDT) is presented containing two anisotropic and one isotropic diffusion tensors. This approach has the ability to detect areas of fiber crossings and resolve the direction of crossing fibers. The mean diffusivity and the ratio of the tensor compartments were merged to one independent parameter by fitting MDT to the diffusion-weighted intensities of a two-point data acquisition scheme. By an F-test between the errors of the standard single diffusion tensor and the more complex MDT, fiber crossings were detected and the more accurate model was chosen voxel by voxel. The performance of crossing detection was compared with the spherical harmonics approach in simulations as well as in vivo. Similar results were found in both methods. The MDT model, however, did not only detect crossings but also yielded the single fiber directions. The FACT algorithm and a probabilistic connectivity algorithm were extended to support the MDT model. For example, a mean angular error smaller than 10 degrees was found for the MDT model in a simulated fiber crossing with an SNR of 80. By tracking the corticospinal tract the MDT-based tracks reached a significantly greater area of the gyrus precentralis. | 10.1002/mrm.20670 |
pubmed_832_21235 | Silk is useful as a drug carrier because of its biocompatibility, tunable degradation, and capacity in maintaining the function of drugs. However, further refinements are still required for silk-based nanoparticles to optimize applications as anticancer drug delivery systems. Here, a novel strategy was developed to prepare silk nanoparticles with improved performance. Unlike previous preparation methods that first obtain silk solutions and then induce nanoparticle formation through different treatments, here silk nanoparticles were directly prepared after a modified dissolution process. The nanoparticles had amorphous structure and homogeneous morphology, as well as improved dispersion in water and PBS solutions and improved pH-dependent drug release behavior when compared with the traditionally prepared silk nanoparticles. These improvements resulted in better uptake of the nanoparticles into cancer cells and higher cytotoxicity against cancer cells. These properties, when combined with the simpler and milder preparation process, indicate potential utility for anticancer drug delivery. | 10.1021/acsbiomaterials.6b00457 |
pubmed_260_24372 | Paracoccidioidomycosis is a chronic progressive infection. It affects mainly the elderly and it is geographically limited to certain areas of Latin America. In Europe it is considered a rare imported infection. Here we report a case of paracoccidioidomycosis that occurred in a 27-year-old Ecuadorian patient living in Spain initially misdiagnosed as blastomycosis. The typical multi-budding yeast cells of Paracoccidioides brasiliensis were observed in Grocott stained samples. This case should alert Spanish mycologists, clinicians and pathologists about the possibility of patients who have travelled or lived outside Spain may suffer paracoccidioidomycosis or other imported mycoses. | 10.1016/s1130-1406(07)70011-6 |
pubmed_307_10221 | Chronic sinonasal foreign bodies present unique surgical challenges including tissue integration and anatomic migration. A patient with a history of multiple surgeries for cleft lip, palate, and nasal deformity presented with radiographic findings of a 4.3-cm linear foreign body traversing the nasal cavity and sphenoid sinus. Mucosalization and integration into the sphenoid rostrum were noted at the time of surgery. Endoscopic surgery techniques facilitated removal of the overlying mucosa and encasing bone, allowing successful surgical extraction. On inspection, the foreign body was consistent with a retained Kirschner wire. Potential pathophysiologic and management implications of this case are discussed. | 10.1597/10-253 |
pubmed_769_3440 | The potential for bias in industry-developed information about noninvasive prenatal testing (NIPT), in addition to the lack of regulatory oversight for this type of product, raises questions about clinical communication and adoption. We identify NIPTs marketed globally and analyze their English-language consumer-oriented brochures to determine whether they meet existing policy and ethical guidance from the Nuffield Council on Bioethics on NIPT marketing, how they establish the legitimacy of the test given the lack of regulatory oversight for NIPT, and whether content differs between the brochures from for-profit and nonprofit entities. In many of these brochures, NIPTs are misrepresented as diagnostic tests, claims lack supporting evidence, regulatory bodies that do not evaluate the test itself are referenced, and clinicians are invoked as authorities on specific NIPTs. Our findings substantiate concerns about the extent to which commercial imperatives operating in the absence of market-access regulation could exacerbate problems of misrepresentation and inaccuracy in marketing materials. | 10.1002/hast.1329 |
pubmed_1131_23686 | Recent molecular studies have revealed a complex microbiota in the dog intestine. Convincing evidence has been reported linking changes in microbial communities to acute and chronic gastrointestinal inflammation, especially in canine inflammatory bowel disease (IBD). The most common microbial changes observed in intestinal inflammation are decreases in the bacterial phyla Firmicutes (i.e., Lachnospiraceae, Ruminococcaceae, and ) and Bacteroidetes, with concurrent increases in Proteobacteria (i.e., ). Due to the important role of microbial-derived metabolites for host health, it is important to elucidate the metabolic consequences of gastrointestinal dysbiosis and physiological pathways implicated in specific disease phenotypes. Metagenomic studies have used shotgun sequencing of DNA as well as phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) to characterize functional changes in the bacterial metagenome in gastrointestinal disease. Furthermore, wide-scale and untargeted measurements of metabolic products derived by the host and the microbiota in intestinal samples allow a better understanding of the functional alterations that occur in gastrointestinal disease. For example, changes in bile acid metabolism and tryptophan catabolism recently have been reported in humans and dogs. Also, metabolites associated with the pentose phosphate pathway were significantly altered in chronic gastrointestinal inflammation and indicate the presence of oxidative stress in dogs with IBD. This review focuses on the advancements made in canine metagenomics and metabolomics and their implications in understanding gastrointestinal disease as well as the development of better treatment approaches. | 10.2527/jas.2015-0029 |
pubmed_311_6260 | OBJECTIVE
To identify the perceived barriers to the implementation of the Australian national guidelines on influenza outbreak management with Sydney Local Health District (SLHD) residential aged care facility (RACF) staff.
METHODS
All SLHD RACFs were invited to participate in a telephone interview. The questionnaire collected information about demographic characteristics and participants' level of agreement with statements regarding perceived barriers to implementing the national guidelines for influenza outbreak management.
RESULTS
Twenty-eight of 61 RACFs (46%) participated in the study. The three most common barriers identified were as follows: scepticism towards staff influenza vaccination (n = 13, 46%); the effort required to read the national guidelines (n = 11, 39%); and lack of infrastructure to physically separate residents during an outbreak (n = 10, 36%).
CONCLUSIONS
We recommend implementing and evaluating programmes which address misconceptions about influenza vaccination amongst RACF staff. Further, all RACF staff, including care staff, should receive targeted education on the role of infection control in influenza outbreak management. | 10.1111/ajag.12595 |
pubmed_516_14966 | Researchers have traditionally relied on self-report questionnaires to assess psychological well-being, but such measures may be unable to differentiate individuals who are genuinely psychologically healthy from those who maintain a facade or illusion of mental health based on denial and self-deception. Prior research suggests that clinically derived assessment procedures that assess implicit psychological processes may have advantages over self-report mental health measures. This prospective study compared the Early Memory Index, an implicit measure of mental health/distress, with a range of familiar self-report scales as predictors of physical health. The Early Memory Index showed significant prospective associations with health service utilization and clinically verified illness. In contrast, self-report measures of mental health, perceived stress, life events stress, and mood states did not predict health outcomes. The findings highlight the limitations of self-report questionnaires and suggest that implicit measures have an important role to play in mental health research. | 10.1097/01.nmd.0000221373.74045.51 |
pubmed_552_18833 | Immunophenotypes and genotypes were analyzed for a case of chronic myelocytic leukemia in blast crisis (BC). In the early stage of BC (early BC), the blasts consisted of lymphoid-myeloid cells, but in the later stage of BC (late BC), they were myeloid cells, morphologically and phenotypically. On Southern blot of DNAs in early BC, a single rearranged fragment of immunoglobulin heavy chain (IgH) genes was detected, whereas IgH genes were in germline configuration in both initial chronic phase and late BC. A clone which had a rearranged IgH gene in early BC, was considered to have co-existed with a clone which had the germline IgH gene. Analysis for bcr genes confirmed that the chronic phase as well as early and late BC were of the same clonal origin. Phenotypic and immunogenotypic analyses, however, revealed that at least two secondary clones emerged from the primary clone. The therapeutic effect against lymphoid population among mixed crisis cells could be evuluated not only phenotypically but also genotypically. | pubmed_552_18833 |
pubmed_1060_9275 | I examined whether the phorbol ester-mediated inhibition of glycerol 3-phosphate dehydrogenase (GPDH) induction could be mimicked by raising the cellular diacylglycerol levels. Phorbol ester tumor promoters and diacylglycerols activate protein kinase C. An increase in radiolabeled diacylglycerol levels in C6 rat glioma cells was observed when cells were prelabeled overnight with [3H]arachidonic acid and treated with either phospholipase C (Clostridium perfringens) or 2-bromooctanoate. The increase was dose dependent. The diacylglycerols competed with [20-3H]phorbol 12,13-dibutyrate in binding to the phorbol ester receptor. A Scatchard analysis of the binding of cells treated with 0.1 unit/ml of phospholipase C demonstrated that the inhibition was mainly due to a decrease in binding affinity and not in the total number of binding sites. 2-Bromooctanoate and phospholipase C, but not the synthetic diacylglycerol 1-oleoyl 2-acetyl glycerol, inhibited the glucocorticoid induction of GPDH levels. Boiled phospholipase C, phospholipase A2, or phospholipase D was ineffective in inhibiting induction, a result suggesting that the inhibition was not due to nonspecific membrane perturbation. Thus, inhibition of the glucocorticoid-mediated increase in GPDH induction is most likely mediated by protein kinase C, and not by an alternate phorbol ester receptor. | 10.1111/j.1471-4159.1987.tb13145.x |
pubmed_851_16650 | Bone morphogenetic proteins (BMPs) belong to the TGF-β super family, and are essential for the regulation of foetal development, tissue differentiation and homeostasis and a multitude of cellular functions. Naturally, this has led to the exploration of aberrance in this highly regulated system as a key factor in tumourigenesis. Originally identified for their role in osteogenesis and bone turnover, attention has been turned to the potential role of BMPs in tumour metastases to, and progression within, the bone niche. This is particularly pertinent to breast cancer, which commonly metastasises to bone, and in which studies have revealed aberrations of both BMP expression and signalling, which correlate clinically with breast cancer progression. Ultimately a BMP profile could provide new prognostic disease markers. As the evidence suggests a role for BMPs in regulating breast tumour cellular function, in particular interactions with tumour stroma and the bone metastatic microenvironment, there may be novel therapeutic potential in targeting BMP signalling in breast cancer. This review provides an update on the current knowledge of BMP abnormalities and their implication in the development and progression of breast cancer, particularly in the disease-specific bone metastasis. | 10.1530/ERC-17-0139 |
pubmed_608_13328 | Colorectal cancer (CRC) is a public health problem worldwide and in Jordan. Statins are cholesterol lowering agents. Beyond their effects, statins use has been reported to reduced risk of several malignances, including CRC. This study aimed to assess the effect of statins on CRC by studying cellular infiltration of Regulatory T Lymphocytes (Tregs) into CRC tissues and their effect on Transforming growth factor beta 1 (TGF-β1) level and on angiogenesis. Fourty seven specimens (25 statins users vs. 22 non-users) were used. Immunohistochemistry was performed to study Tregs infiltration using their marker, fork head transcription factor, and angiogenesis using CD31 as a marker. TGF-β1 levels were measured using ELISA. Results revealed that statins use was associated with more Tregs infiltration, less angiogenesis but no difference in TGF-β1 content in tumor tissue. When results were further stratified according to stage of disease, more Tregs infiltration was significantly noticed in advanced disease but not in early disease. In addition, more angiogenesis inhibition was noticed in early disease but not in advanced disease. Same stage-dependence wasn't noticed with TGF-β1 expression. In early disease, reduction of angiogenesis mediated by statins might lead to reduction of tumor aggressiveness. On the other hand, Tregs infiltration into tumor mediated by statins might reduce cancer aggressiveness in advanced disease. These results suggest that statins might be used in the treatment of CRC. | 10.18632/oncotarget.26293 |
pubmed_203_6541 | An aneurysm is a local artery ballooning greater than 50% of its nominal diameter with a risk of sudden rupture. Minimally invasive repair can be achieved by inserting surgically a stent-graft, called an endovascular graft (EVG), which is either straight tubular curved tubular or bifurcating. However post-procedural complications may arise because of elevated stagnant blood pressure in the cavity, i.e., the sac formed by the EVG and the weakened aneurysm wall In order to investigate the underlying mechanisms leading to elevated sac-pressures and hence to potentially dangerous wall stress levels and aneurysm rupture, a transient 3-D stented abdominal aortic aneurysm model and a coupled fluid-structure interaction solver were employed. Simulation results indicate that, even without the presence of endoleaks (blood flowing into the cavity), elevated sac pressure can occur due to complex fluid-structure interactions between the luminal blood flow, EVG wall, intra-sac stagnant blood, including an intra-luminal thrombus, and the aneurysm wall. Nevertheless, the impact of sac-blood volume changes due to leakage on the sac pressure and aneurysm wall stress was analyzed as well. While blood flow conditions, EVG and aneurysm geometries as well as wall mechanical properties play important roles in both sac pressure and wall stress generation, it is always the maximum wall stress that is one of the most critical parameters in aneurysm rupture prediction. All simulation results are in agreement with experimental data and clinical observations. | 10.1115/1.1934040 |
pubmed_176_18636 | AIM OF THE STUDY
To examine the development of door-to-angiography time (DTA) and to evaluate the impact of door-to-angiography time in patients with ST-elevation myocardial infarction (STEMI) on hospital and one-year mortality.
METHODS AND RESULTS
From 1994 to 2008, 5078 patients (pts) and known DTA with acute ST-elevation myocardial infarction were enrolled into the MITRAplus and OPTAMI registry in Germany. Our data showed a reduction of the door-to- angiography time from 80 min to 64 min in the last 14 years (P < 0.001). Over 80% of patients received an angiography less than two hours after admission. The main predictor of a shorter door-to-balloon time was a hypotension with a blood pressure lower than 100 mmHg (OR 1.46, 95%CI: 1.08-1.91). Whereas a history of prior myocardial infarction (OR 0.61, 95%CI: 0.45-0.84), a previous coronary bypass grafting (OR 0.55, 95%CI: 0.33-0.91), age older than 75 years (OR 0.78, 95%CI: 0.62-0.99) and a pre-hospital delay more than three hours (OR 0.78, 95%CI: 0.66-0.93) were independent predictors for a longer of the door-to-balloon time. In the multivariate regression analysis no influence was detected of door-to-angiography time on hospital or one-year mortality.
CONCLUSION
The DTA decreased in the last 14 years and is actually very short in Germany. We indentified predictors of a longer door-to-angiography time in clinical practice. Given the overall short in-hospital delay, the observed door-to-angiography time did not have influence on hospital and mid term mortality. | 10.3109/17482941.2010.551133 |
pubmed_1048_8439 | To investigate immuno-chemotherapy for elderly immuno-competent patients (⩾65 years) with newly diagnosed primary central nervous system lymphoma, we conducted a multicentre single-arm trial. One cycle consisted of rituximab (375 mg/m2, days 1, 15, 29), high-dose methotrexate (3 g/m2 days 2, 16, 30), procarbazine (60 mg/m2 days 2-11) and lomustine (110 mg/m2, day 2)-R-MPL protocol. Owing to infectious complications, we omitted lomustine during the study and consecutive patients were treated with the R-MP protocol. Three cycles were scheduled and repeated on day 43. Subsequently, patients commenced 4 weekly maintenance treatment with procarbazine (100 mg for 5 days). Primary end point was complete remission (CR) after 3 cycles. We included 107 patients (69 treated with R-MPL and 38 with R-MP). In all, 38/107 patients achieved CR (35.5%) and 15 (14.0%) achieved partial remission. R-MP was associated with a lower CR rate (31.6%) compared with R-MPL (37.7%), but respective 2-year progression-free survival (All 37.3%; R-MP 34.9%; R-MPL 38.8%) and overall survival (All 47.0%; R-MP 47.7%; R-MPL 46.0%) rates were similar. R-MP was associated with less ⩾grade 3 toxicities compared with R-MPL (71.1% vs 87.0%). R-MP is more feasible while still associated with similar efficacy compared with R-MPL and warrants further improvement in future studies. | 10.1038/leu.2016.334 |
pubmed_1027_16534 | Cyclins are key components of the cell cycle progression machinery. They activate their partner-dependent kinases (CDKs) and target them to respective substrate proteins within the cell. CDK-mediated phosphorylation of specific sets of proteins drives the cell through particular phases or checkpoints of the cell cycle. During unperturbed growth of normal cells, the timing of expression of several cyclins is discontinuous, occurring at discrete and well-defined periods of the cell cycle. Immunocytochemical detection of cyclins in relation to cell cycle position (DNA content) by multiparameter flow cytometric techniques has provided a new approach to cell cycle studies. This approach, like no other method, can be used to detect the "unscheduled" expression of cyclins, namely, the presentation of G1 cyclins by cells in G2/M and of G2/M cyclins by G1 cells, without the need for cell synchronization. By use of multiparameter flow cytometric and laser scanning cytometric analysis, we correlated the expression of cyclin B1 with cell cycle position in normal lymphocytes stimulated to proliferate by the mitogen phytohemagglutinin and in 28 primary human tumors of different organ and type. Eighteen of the 28 tumors expressed the cyclin B1 in more than 5% of cells (B1 positive), and the rest showed cyclin expression from 2.1 to 5% (B1 negative). In normal lymphocytes, the expression of cyclin B1 was restricted to very late S and G2 + M phases of the cell cycle. In 15 of 18 primary tumors studied, the expression of cyclin B1 was "unscheduled" (unrestricted to particular phases of the cycle). The data suggest that the "unscheduled" expression of cyclin B1 might be a common defect in neoplasia. | pubmed_1027_16534 |
pubmed_603_1070 | Alzheimer's disease is the leading cause of dementia in the elderly and is defined by two pathological hallmarks; the accumulation of aggregated amyloid beta and excessively phosphorylated Tau proteins. The etiology of Alzheimer's disease progression is still debated, however, increased oxidative stress is an early and sustained event that underlies much of the neurotoxicity and consequent neuronal loss. Amyloid beta is a metal binding protein and copper, zinc and iron promote amyloid beta oligomer formation. Additionally, copper and iron are redox active and can generate reactive oxygen species via Fenton (and Fenton-like chemistry) and the Haber-Weiss reaction. Copper, zinc and iron are naturally abundant in the brain but Alzheimer's disease brain contains elevated concentrations of these metals in areas of amyloid plaque pathology. Amyloid beta can become pro-oxidant and when complexed to copper or iron it can generate hydrogen peroxide. Accumulating evidence suggests that copper, zinc, and iron homeostasis may become perturbed in Alzheimer's disease and could underlie an increased oxidative stress burden. In this review we discuss oxidative/nitrosative stress in Alzheimer's disease with a focus on the role that metals play in this process. Recent studies have started to elucidate molecular links with oxidative/nitrosative stress and Alzheimer's disease. Finally, we discuss metal binding compounds that are designed to cross the blood brain barrier and restore metal homeostasis as potential Alzheimer's disease therapeutics. | pubmed_603_1070 |
pubmed_80_575 | Background Learning to identify and address social determinants of health (SDH) is a crucial component of pediatric residency training. A virtual tour of an impoverished neighborhood previously demonstrated efficacy in increasing residents' self-assessed knowledge and competence, but its impact on performance has not yet been reported. Online simulated cases are emerging as feasible assessment tools to measure trainees' skills across various healthcare settings. We developed online simulated cases to evaluate residents' retention of the virtual tour's key SDH-related learning objectives 1 month after completing this curriculum. Methods Three online simulated cases with interpolated open-ended questions were created to assess residents' ability to identify SDH, recommend appropriate resources, and display empathy. Scoring rubrics to objectively evaluate responses were developed and borderline scores were decided by a team of educators. Results 19 residents participated. Mean scores for all cases exceeded pre-established borderline scores (statistically significant in two of the three cases). More than 90% of residents identified relevant SDH in the primary care and emergency department cases. Ninety-five percent of residents recommended appropriate resources in all cases, and 89% displayed empathy. Discussion Residents' performance in online simulated cases demonstrated retention and application of the virtual tour's learning objectives, including recognizing SDH, offering appropriate resources, and displaying empathy, which supports the long-term effectiveness of the virtual tour curriculum to train pediatricians about SDH. Online simulated cases provided a standardized and cost-effective way to measure residents' skills related to curricular uptake, suggesting that this assessment approach may be adapted to evaluate other educational interventions. | 10.1007/s10995-019-02790-9 |
pubmed_31_8648 | BACKGROUND
There is currently no international recommendation for the admission or treatment of the critically ill older patients over 80 years of age in the intensive care unit (ICU), and there is no valid prognostic severity score that includes specific geriatric assessments.
MAIN BODY
In this review, we report recent literature focusing on older critically ill patients in order to help physicians in the multiple-step decision-making process. It is unclear under what conditions older patients may benefit from ICU admission. Consequently, there is a wide variation in triage practices, treatment intensity levels, end-of-life practices, discharge practices and frequency of geriatrician's involvement among institutions and clinicians. In this review, we discuss important steps in caring for critically ill older patients, from the triage to long-term outcome, with a focus on specific conditions in the very old patients.
CONCLUSION
According to previous considerations, we provide an algorithm presented as a guide to aid in the decision-making process for the caring of the critically ill older patients. | 10.1186/s13613-018-0458-7 |
pubmed_522_1167 | PURPOSE
To describe the optical implications of the aberration pattern of a keratoconic eye implanted with an intrastromal corneal ring (Ferrara ring).
METHODS
A 32-year-old man with bilateral keratoconus had a Ferrara intrastromal corneal ring implanted in his right eye. Surgery was uneventful and both uncorrected (UCVA) and best spectacle-corrected (BSCVA) visual acuity improved. Corneal topography was performed before and after surgery. Wavefront measurements were performed 1 month after the procedure in both eyes for comparison. The point spread function, modulation transfer function (MTF), and convolved acuity chart were analyzed.
RESULTS
The right eye--implanted with the intrastromal Ferrara ring--had high root-mean-square (RMS) values for higher order aberrations. The left eye-keratoconus without an intrastromal ring-had moderate values. Point spread function, MTF, and convolution acuity charts are presented for each eye, with the latter two showing improved visual function in the implanted eye, despite a higher aberration value.
CONCLUSION
The wavefront measurement device captured aberrations even in a highly aberrated eye. Despite better UCVA and BSCVA, the Ferrara ring notably increased higher order aberrations compared to the fellow eye, but with a more uniform central pattern. In this case, the larger RMS value was a poor predictor of good visual function; other metrics better predicted the patient's subjective response. Metrics other than RMS error may be necessary to better correlate aberration value with visual satisfaction in some eyes. | 10.3928/1081-597X-20041101-11 |
pubmed_38_15301 | We describe the benefit of using reconstructed ancestral sequences (RAS) on resequencing microarrays for rapid pathogen identification, with Enterobacteriaceae rpoB sequences as a model. Our results demonstrate a sharp improvement of call rate and accuracy when using RASs as compared to extant sequences. This improvement was attributed to the lower sequence divergence of RASs, which also expanded the sequence space covered by the microarray. Extension of this novel microarray design strategy to viruses, antimicrobial resistance elements or toxins is straightforward. | 10.1371/journal.pone.0015243 |
pubmed_700_20557 | We have visualized the nuclear pore complex (NPCx) three-dimensionally by quick-freeze, deep etching and suggest that NPCx is composed of four rings and associated filaments. The rings were located at the cytoplasmic side, at the nucleoplasmic side, and at the pore waist as well. Some of the filaments emanated toward the cytoplasm, some sprawled over the cytoplasmic face of the nuclear membrane, and some intervened the rings. The emanating filaments were considered to be vimentin filaments judging from the replica and thin-sectioned image. | pubmed_700_20557 |
pubmed_1132_21396 | Chain-of-state methods are becoming important tools in studying the chemical reaction mechanisms, especially for biomacromolecules. In this article, three chain-of-state methods, nudged elastic band (NEB) method and the replica path method with restraints or constraints, were tested and compared using three model systems with various sizes and at different levels of theory: alanine dipeptide isomerization, β-alanine intramolecular condensation, and the matrix metalloproteinase 2 inhibition mechanism. The levels of theory used to describe the three model systems include molecular mechanics (MM), quantum mechanics (QM), and combined quantum mechanics and molecular mechanics (QM/MM). All three methods could correctly determine a reaction path with reasonable estimation of reaction barriers in most cases. The RMSD measurement with additional weighting schemes provides practically infinite choices of reaction coordinates to describe the reaction progress. These findings demonstrate that the chain-of-state methods are powerful tools when being used carefully to generate a plausible reaction mechanism with full pathway for complex systems at an affordable computational cost. | 10.1021/ct3006248 |
pubmed_203_5187 | OBJECTIVE
To assess the level of awareness and correlates of use of family planning services among sexually active breastfeeding mothers attending an infant welfare clinic.
DESIGN
Cross-sectional descriptive design.
SETTING
Infant welfare clinic of the urban comprehensive health centre, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria.
SUBJECTS
Mothers of breast feeding infants aged 8-11 months attending the infant welfare clinic.
RESULTS
Awareness of family planning was quite high (95.5%) while current family planning use was quite low (13%). Although the proportion of women who planned for future use of family planning in the sample was high (64%), all current non-users (86.6%) met the criteria for unmet need for family planning. Parity and the number of living children were the only socio-demographic correlates of the respondents that significantly influenced family planning acceptance (P < 0.05).
CONCLUSION
There is a high level of contraceptive awareness but low contraceptive use among breast feeding mothers in Nigeria, with a majority of non-users depending on the perceived contraceptive effects of breastfeeding. | 10.4314/eamj.v82i5.9315 |
pubmed_622_8393 | OBJECTIVE
To determine the efficacy of various intravenous immunoglobulin (IVIG) protocols used in the treatment of autoimmune and chronic inflammatory disorders.
DATA SOURCES
Literature retrieval was accessed through MEDLINE (November 1984-March 2007) and a search was conducted using the term intravenous immunoglobulin. References cited in the selected articles were also reviewed.
STUDY SELECTION AND DATA EXTRACTION
Inclusion criteria for studies were (1) English language, (2) randomized controlled trials, (3) defined protocols, (4) a minimum of 15 patients, and (5) objective criteria provided to assess clinical outcomes and course.
DATA SYNTHESIS
The therapeutic efficacy of IVIG therapy is well established, and defined protocols exist for treatment of Kawasaki disease, immune thrombocytopenic purpura, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and autoimmune mucocutaneous blistering diseases. In the absence of a defined protocol, studies have demonstrated that IVIG therapy is effective in the treatment of myasthenia gravis, dermatomyositis, stiff person syndrome, antineutrophil cytoplasmic antibody positive systemic vasculitides, Graves' ophthalmopathy, and certain forms of systemic lupus erythematosus. It might also be of benefit in some patients with relapsing-remitting multiple sclerosis. The outcomes are variable in these studies. In toxic epidermal necrolysis and Stevens-Johnson syndrome, use of IVIG has dramatically influenced clinical response and reduced mortality.
CONCLUSIONS
The cumulative evidence suggests that the clinical outcomes observed are significantly influenced by the use of a defined protocol. There is a need for multicenter trials approved by the Food and Drug Administration to better define the role of IVIG in many disease states. Such studies would be able to establish the indications for use, optimal dose, frequency of infusions, duration of therapy, and need for gradual withdrawal versus sudden cessation. Defined protocols resulting from the study of a large cohort of patients often convince insurance companies to create policies that provide access to IVIG therapy. | 10.1345/aph.1K037 |
pubmed_695_4105 | In nanocomposites, the adhesion between nanofillers and the polymeric matrix is key to the mechanical properties. The strength and spatial distribution of the adhesive layer around the nanofillers are important, particularly the presence of chemical bonding between the nanofillers and matrix. In this work, we studied a styrene-butadiene rubber composite filled with silica nanoparticles to visualize the spatial distribution of the adhesive layer. A silane coupling agent (SCA) was added to the nanocomposite for strong adhesion. The reaction involving the SCA on the silica surface was investigated by scanning transmission electron microscopy combined with electron energy-loss spectroscopy. Si-L2,3 spectra of the silica-filled rubber nanocomposite without the SCA were the same around the nanofillers, whereas in the nanocomposite containing the SCA the spectra were position-dependent. The spectra were fitted with the intensity profiles of the Si-L2,3 spectra of silica and SCA by multiple linear least-squares fitting. The fitting coefficients of silica and SCA were used to map the spatial distribution of the chemical bonding between silica and rubber chains. Chemical bonding was observed around the silica nanoparticles but not in the SBR matrix region, providing direct evidence of the reinforcing mechanism in the silica-filled rubber nanocomposite. | 10.1038/s41598-020-78393-0 |
pubmed_432_10828 | A retrospective study looking for an history of somnambulism in childhood, in a population of 122 patients with migraine, and 110 patients with non-migraine headache has been performed. A very high frequency of somnambulism in patients with migraine was found whereas frequency of somnambulism in patients with non-migraine headache was similar to that of the general population. The probability that a sleepwalking child acquires a migraine is greater when she is a girl. Migraine is then often of the ophthalmic type. Somnambulism and migraine appear at different ages, the former in the late infancy, the latter in childhood and both could be due to a disorder of serotonin metabolism. The authors suggest that somnambulism be considered as an accessory criterion for the diagnosis of migrainous disease. | pubmed_432_10828 |
pubmed_17_8472 | This article presents an image analysis-based approach to the statistical characterization of morphological features in layer-by-layer (LBL) polymer films, which depend on the experimental conditions of fabrication. The method is based on the recently introduced concept of exact dilations. This concept allows the precise determination of all possible parallel contours around any general object and, as a consequence, the respective fully accurate Voronoi partition defined by the objects. With the use of a fast wavefront propagation scheme, such diagrams can be obtained at high speed. The method has been applied to statistically characterize features such as grain size and distribution on LBL polymer films. To do this, the polymer surface is tracked from its highest z values downward to its bottom, and each new connected component is detected as a Voronoi seed. Through determination of equivalent radii of the Voronoi cells, the probability density function characterizing the distribution of the domain radius can then be obtained. | 10.1166/jnn.2003.197 |
pubmed_917_15304 | Antibodies to the preS2 region of the hepatitis B virus (HBV) envelope protein and to human serum albumin (HSA) were allegedly detected at about the same level in sera of humans with acute or chronic hepatitis B [Hellström et al., 1986]. It was claimed that anti-HSA arises as a result of an immune response to the preS2 sequence and that it was involved in hepatocellular damage. Over 100 sera from animals and humans immunized with HBsAg containing preS2 sequences, or with synthetic peptides from the preS1, preS2, and S regions of the HBV env protein were assayed for anti-HSA. The results revealed the following: 1) Immunization with the native preS2 sequence or with unconjugated synthetic peptides derived from that sequence does not result in elicitation of anti-HSA. Therefore the alleged appearance of anti-HSA during hepatitis B cannot be directly related to an anti-preS2-specific immune response. 2) Some synthetic peptides, whether or not they were derived from the preS2 sequence, when linked to certain carriers, but not to others, elicited in rabbits an anti-HSA response, which was markedly lower than the response to the homologous peptide. These anti-HSA antibodies could be separated from anti-preS2-specific antibodies by affinity chromatography and did not recognize the synthetic peptide used for immunization. The use in active immunoprophylaxis of hepatitis B of unconjugated peptides from the preS2 sequence with proven high immunogenicity will avoid carrier/linker-mediated induction of antibodies not relevant to protection against HBV. | 10.1002/jmv.1890240203 |
pubmed_805_2803 | Of the many procedures for treating painful neuromas, resection and proximal translocation are the most usual techniques, but these can decrease distal sensibility increasing deafferentation pain. In cases of intricate pain (nociception plus deafferentation), certain types of flaps allow the treatment of both components of the pain. We have used 30 such flaps in 28 patients: local flaps (exchange, advancement or lasso island flaps) and distant flaps (free "custom-made" toe flaps). The results of the different techniques provides 86.6% excellent or good results. | 10.1016/0266-7681(91)90121-4 |
pubmed_170_2888 | BACKGROUND
Plasmodium vivax and Plasmodium falciparum are the major causative agents of malaria. While knowledge of the genetic structure of malaria parasites is useful for understanding the evolution of parasite virulence, designing anti-malarial vaccines and assessing the impact of malaria control measures, there is a paucity of information on genetic diversity of these two malaria parasites in Pakistan. This study sought to shed some light on the genetic structure of P. vivax and P. falciparum in this understudied region.
METHODS
The genetic diversities of P. vivax and P. falciparum populations from the densely populated, malaria-endemic Bannu district of Pakistan were evaluated by analysis of their merozoite surface protein (msp) genes by PCR-RFLP. Specifically, the Pvmsp-3alpha and Pvmsp-3beta genes of P. vivax and the Pfmsp-1 and Pfmsp-2 genes of P. falciparum were analysed.
RESULTS
In P. vivax, genotyping of Pvmsp-3alpha and Pvmsp-3beta genes showed a high level of diversity at these loci. Four distinct allele groups: A (1.9 kb), B (1.5 kb), C (1.2 kb), and D (0.3 kb) were detected for Pvmsp-3alpha, type A being the most prevalent (82%). Conversely, amplification of the P. vivax msp-3beta locus produced two allele groups: A (1.7-2.2 kb, 62%) and B (1.4-1.5 kb, 33%), with 5% mixed-strain infections. Restriction analysis of Pvmsp-3alpha and Pvmsp-3beta yielded 12 and 8 distinct alleles, respectively, with a combined mixed genotype prevalence of 20%. In P. falciparum, all three known genotypes of Pfmsp-1 and two of Pfmsp-2 were observed, with MAD20 occurring in 67% and 3D7/IC in 65% of the isolates, respectively. Overall, 24% P. falciparum samples exhibited mixed-strain infections.
CONCLUSION
These results indicate that both P. vivax and P. falciparum populations in Pakistan are highly diverse. | 10.1186/1475-2875-9-112 |
pubmed_401_2912 | Background
The worst SARS-CoV-2 outbreak in Sri Lanka was due to the two Sri Lankan delta sub-lineages AY.28 and AY.104. We proceeded to further characterize the mutations and clinical disease severity of these two sub-lineages.
Methods
705 delta SARS-CoV-2 genomes sequenced by our laboratory from mid-May to November 2021 using Illumina and Oxford Nanopore were included in the analysis. The clinical disease severity of 440/705 individuals were further analyzed to determine if infection with either AY.28 or AY.104 was associated with more severe disease. Sub-genomic RNA (sg-RNA) expression was analyzed using periscope.
Results
AY.28 was the dominant variant throughout the outbreak, accounting for 67.7% of infections during the peak of the outbreak. AY.28 had three lineage defining mutations in the spike protein: A222V (92.80%), A701S (88.06%), and A1078S (92.04%) and seven in the ORF1a: R24C, K634N, P1640L, A2994V, A3209V, V3718A, and T3750I. AY.104 was characterized by the high prevalence of T95I (90.81%) and T572L (65.01%) mutations in the spike protein and by the absence of P1640L (94.28%) in ORF1a with the presence of A1918V (98.58%) mutation. The mean sgRNA expression levels of ORF6 in AY.28 were significantly higher compared to AY.104 (p < 0.0001) and B.1.617.2 (p < 0.01). Also, ORF3a showed significantly higher sgRNA expression in AY.28 compared to AY.104 (p < 0.0001). There was no difference in the clinical disease severity or duration of hospitalization in individuals infected with these sub lineages.
Conclusions
Therefore, AY.28 and AY.104 appear to have a fitness advantage over the parental delta variant (B.1.617.2), while AY.28 also had a higher expression of sg-RNA compared to other sub-lineages. The clinical implications of these should be further investigated. | 10.3389/fpubh.2022.873633 |
pubmed_618_24532 | Numerous treatments have been used in the management of corneal chemical burns; however, no optimal treatment for corneal chemical burns currently exists. The present study investigated the effects of topical chondrocyte-derived extracellular matrix (CD-ECM) treatment on corneal wound healing, using an alkali burn mouse model. Topical treatment with CD-ECM was shown to reduce corneal opacity following an alkali burn. A histological examination observed the presence of regenerated epithelial cells and a small number of inflammatory cells in the corneas of CD-ECM-treated mice. The majority of the inflammatory cells present in the corneas of the phosphate-buffered saline (PBS)-treated mice were neutrophils that expressed matrix metalloproteinase (MMP)-9. The amount of neutrophils was significantly reduced in the corneas of the CD-ECM-treated mice. Furthermore, the expression levels of interleukin (IL)-8 were significantly reduced in the CD-ECM treatment group, but not in the mice that received the PBS treatment. The results of the present study indicate that CD-ECM treatment may accelerate wound healing in a model of alkali burn-induced corneal injury. The therapeutic mechanism may be associated with accelerated reepithelialization and reduced recruitment of MMP-9-expressing neutrophils, through inhibiting the production of IL-8. | 10.3892/mmr.2014.2722 |
pubmed_740_22853 | Nuclear fusion is regularly created in spherical plasma compressions driven by multi-kilojoule pulses from the world's largest lasers. Here we demonstrate a dense fusion environment created by irradiating arrays of deuterated nanostructures with joule-level pulses from a compact ultrafast laser. The irradiation of ordered deuterated polyethylene nanowires arrays with femtosecond pulses of relativistic intensity creates ultra-high energy density plasmas in which deuterons (D) are accelerated up to MeV energies, efficiently driving D-D fusion reactions and ultrafast neutron bursts. We measure up to 2 × 106 fusion neutrons per joule, an increase of about 500 times with respect to flat solid targets, a record yield for joule-level lasers. Moreover, in accordance with simulation predictions, we observe a rapid increase in neutron yield with laser pulse energy. The results will impact nuclear science and high energy density research and can lead to bright ultrafast quasi-monoenergetic neutron point sources for imaging and materials studies. | 10.1038/s41467-018-03445-z |
pubmed_884_2765 | Human erythrocyte 5'-AMP aminohydrolase has been obtained using phosphocellulose chromatography and affinity chromatography on a GTP-agarose column to yield a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme has a molecular weight of 285,000, and is comprised of four subunits. Since limited quantities of the homogeneous enzyme were available, the kinetic properties of a nonhomogeneous preparation purified about 20,000-fold over the red blood cell lysate by phosphocellulose chromatography were examined. Like the muscle enzyme, it exhibits a sigmoid AMP saturation curve in the absence of activating monovalent cations; a hyperbolic saturation curve is observed in the presence of 0.15 M KCl. Activation by monovalent cations and ATP, and inhibition by Pi, PPi, GDP, GTP, and 2,3-diphosphoglyceric acid were studied in more detail. | pubmed_884_2765 |
pubmed_866_2222 | An acute increase in blood flow triggers flow-mediated dilation (FMD), which is mainly mediated by endothelial nitric oxide synthase (eNOS). A long-term increase in blood flow chronically enlarges the arterial lumen, a process called arteriogenesis. In several common human diseases, these processes are disrupted for as yet unknown reasons. Here, we asked whether β1 integrin, a mechanosensory protein in endothelial cells, is required for FMD and arteriogenesis in the ischemic hindlimb. Permanent ligation of the femoral artery in C57BL/6 J mice enlarged pre-existing collateral arteries and increased numbers of arterioles in the thigh. In the lower leg, the numbers of capillaries increased. Notably, injection of β1 integrin-blocking antibody or tamoxifen-induced endothelial cell-specific deletion of the gene for β1 integrin (Itgb1) inhibited both arteriogenesis and angiogenesis. Using high frequency ultrasound, we demonstrated that β1 integrin-blocking antibody or endothelial cell-specific depletion of β1 integrin attenuated FMD of the femoral artery, and blocking of β1 integrin function did not further decrease FMD in eNOS-deficient mice. Our data suggest that endothelial β1 integrin is required for both acute and chronic widening of the arterial lumen in response to hindlimb ischemia, potentially via functional interaction with eNOS. | 10.1038/s41598-019-53137-x |
pubmed_506_20061 | The sequence of redox reactions in the natural environment generally follows the electron affinity of the electron acceptors present and can be rationalized by the redox potentials of the appropriate half-reactions. Answering the question how halogenated aromatics fit into this sequence requires information on their Gibbs free energy of formation values. In 1992 Gibbs free energy data for various classes of halogenated aromatic compounds were systematically explored for the first time based on Benson's group contribution method. Since then more accurate quantum chemical calculation methods have become available. Here we use these methods to estimate enthalpy and Gibbs free energy of formation values of all chlorinated and brominated phenols. These data and similar state-of-the-art datasets for halogenated benzenes and benzoates were then used to calculate two-electron redox potentials of halogenated aromatics for standard conditions and for pH 7. The results underline the need to take speciation into consideration when evaluating redox potentials at pH 7 and highlight the fact that halogenated aromatics are excellent electron acceptors in aqueous environments. | 10.1007/s10532-014-9710-5 |
pubmed_946_5286 | Two per cent and 4% solutions of sodium cromoglycate eye drops were compared in patients with bilateral vernal keratoconjunctivitis. No difference in efficacy between the two solutions could be detected on the analysis of diary card scores or clinical assessments. The opinions of efficacy and treatment preferences recorded by patients and clinician at the end of the trial were very similar for each solution. Side effects were generally minor, usually relating to stinging following application of the eye drops. | 10.3109/02713688209020009 |
pubmed_687_2373 | A detailed description is given of the method of combustion analysis for carbon and hydrogen to determine the composition of a copolymer from its carbon-hydrogen ratio. The apparatus and procedures have been developed at the National Bureau of Standards over a period of years. The method has been applied chiefly to determine what fraction of a styrene-butadiene copolymer is derived from styrene. Minor ingredients are removed by extraction, with the exception of the bound mercaptan residue for which correction must be made. The amount of bound mercaptan residue is determined from measurements of the sulfur content of the copolymer by the Carius method. Measurements are made of the oxygen content and the ash content, although these do not enter into the calculations. The standard deviation of a measurement of carbon-hydrogen ratio is approximately 0.0010 and is independent of styrene content. This corresponds to a standard deviation of about 0.036-percent bound styrene for polymers of low styrene content and 0.018 percent for polymers of high styrene content. The accuracy of the method is demonstrated by the fact that observations of carbon-hydrogen ratio for four out of five samples of polybutadiene differed by less than one standard deviation from the theoretical value. | 10.6028/jres.064A.015 |
pubmed_990_4105 | This study explores the issue of violence experienced by staff in the learning disability service of an NHS Trust. Based on the literature review a questionnaire survey was sent to all staff employed in the Trust's learning disability service (n = 295). The questionnaire sought: background details of respondents; numerical incidences and types of violence experienced over the previous 12 months; reporting mechanisms; reactions to and impact of violence on individuals and their work; support received. Vignettes provide a rich picture of the types of violent incidences and their impact. The findings show that 81% of staff in the learning disability service had experienced violence in the previous 12 months. Many had numerous experiences of violence. New and inexperienced staff are particularly vulnerable. Training and support systems are, on the whole, limited. Support received from colleagues is generally regarded as more helpful than that of line management. To explore good practice elsewhere, semi-structured interviews were held with individuals working with potentially violent clients in organizations other than the learning disability service. Suggestions are offered for putting in place human resource strategies to reduce the incidences of violence and provide appropriate post-incident support for staff on a continuing basis. | 10.3109/09638289809166060 |
pubmed_179_1872 | In the United States, Black gay and bisexual men account for a quarter of HIV infections and face intersecting social and structural stigmas along the axes of race, sexuality and class. For those diagnosed with HIV, these inequities shape their lived experiences which include HIV disclosure. Public health has privileged HIV status disclosure as the appropriate moral and responsible choice to protect sex partners, reduce stigma and obtain social support. Though little is known about the emotional aspects of HIV disclosure for Black gay and bisexual men, or how they are shaped by social and structural contexts. Using the frameworks of healthism and emotion work, I explore HIV disclosure among a sample of 30 Black gay and bisexual men living with HIV in the Deep South. Drawing on in-depth, qualitative interviews, I identify the emotion work that men engaged in to manage their own emotions and protect the emotions of others before, during and after disclosure or nondisclosure. These findings challenge public health research that has explored disclosure as discrete measurable events by illustrating how HIV disclosure is embedded in ongoing social and structural relations and provide insights that can guide new approaches focused on structural inequities that constitute HIV disclosure. | 10.1111/1467-9566.13372 |
pubmed_262_11264 | We report the focusing of a normally incident plane wave of 405 nm through a Ag/dielectric annular ring structure, using finite-difference time domain analysis. We first study the dependency of the focusing efficiency on slit width when the incident wave is transmitted through a single ring whose slit is filled with a dielectric. Then, light focusing by the multiple-ring structure is investigated as a function of the dielectric thickness. It is observed that the focusing is tunable between near-field and quasi-far-field regimes in the Ag/dielectric layered annular ring structure. Also, the focal intensities are remarkably enhanced by the addition of the dielectric layer, showing a Fabry-Perot-like resonance with respect to the thickness of the dielectric layer. The controllable near-field and far-field focusing offers more flexibility for applications of future nano-optic devices. | 10.1364/AO.49.000950 |
pubmed_708_24086 | Venous disease of the orbit is a rare occurrence which can become manifest in a variety of ways including an arteriovenous aneurysm or fistula, a cavernous sinus or superior ophthalmic vein thrombosis, and an orbital varix, with and without thrombosis. Three patients had proptosis due to orbital varix thrombosis. The onset, degree of pain, and presence of diplopia were all variable. In two of three patients, computed tomographic (CT) scans showed lesions reminiscent of cavernous hemangiomas. The clinical, radiographic, surgical, and histopathologic features of this entity are described and discussed and a hypothesis is proposed to explain the pathophysiology of orbital varix thrombosis. | 10.1016/s0161-6420(90)32615-5 |
pubmed_402_10454 | 1 ,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] negatively regulates expression of the avian PTH (aPTH) gene transcript, and a vitamin D response element (VDRE) near the promoter of the aPTH gene had previously been identified. The present report assessed whether the negative activity imparted by the aPTH VDRE could be converted to a positive transcriptional response through selective mutations introduced into the element. The tested sequences were derived from individual and combined mutations to 2 bp in the 3'-half of the direct repeat element, GGGTCAggaGGGTGT. Cold competition experiments using mutant and wild-type oligonucleotides in the mobility shift assay revealed minor differences in the ability of any of these sequences to compete for binding to a heterodimer complex comprised of recombinant proteins. Ethylation interference footprint analysis for each of the mutants produced unique patterns over the 3'-half-sites that were distinct from the weak, wild-type footprint. Transcriptional outcomes evaluated from a chloramphenicol acetyltransferase reporter construct utilizing the aPTH promoter found that the individual T-->A mutant produced an attenuated negative transcriptional response while the G-->C mutant resulted in a reproducibly weak positive transcriptional outcome. The double mutant, however, yielded a 4-fold increase in transcription, similar to the 7-fold increase observed from an analogous construct using the human osteocalcin VDRE. UV light crosslinking to gapped oligonucleotides assessed the polarity of heterodimer binding to the wild-type and double mutant sequences and was consistent with the vitamin D receptor preferentially binding to the 5'-half of both elements. Finally, DNA affinity chromatography was used to immobilize heterodimer complexes bound to the wild-type and double mutant sequences as bait to identify proteins that may preferentially interact with these DNA-bound heterodimers. This analysis revealed the presence of a p160 protein that specifically interacted with the heterodimer bound to the wild-type VDRE, but was absent from complexes bound to response elements associated with positive transcriptional activity. Thus, the sequence of the individual VDRE appears to play an active role in dictating transcriptional responses that may be mediated by altering the ability of a vitamin D receptor heterodimer to interact with accessory factor proteins. | 10.1210/mend.13.3.0249 |
pubmed_666_906 | Sustainable development is driving a rapid focus shift in the wastewater and organic waste treatment sectors, from a "removal and disposal" approach towards the recovery and reuse of water, energy and materials (e.g. carbon or nutrients). Purple phototrophic bacteria (PPB) are receiving increasing attention due to their capability of growing photoheterotrophically under anaerobic conditions. Using light as energy source, PPB can simultaneously assimilate carbon and nutrients at high efficiencies (with biomass yields close to unity (1 g CODbiomass·g CODremoved-1)), facilitating the maximum recovery of these resources as different value-added products. The effective use of infrared light enables selective PPB enrichment in non-sterile conditions, without competition with other phototrophs such as microalgae if ultraviolet-visible wavelengths are filtered. This review reunites results systematically gathered from over 177 scientific articles, aiming at producing generalized conclusions. The most critical aspects of PPB-based production and valorisation processes are addressed, including: (i) the identification of the main challenges and potentials of different growth strategies, (ii) a critical analysis of the production of value-added compounds, (iii) a comparison of the different value-added products, (iv) insights into the general challenges and opportunities and (v) recommendations for future research and development towards practical implementation. To date, most of the work has not been executed under real-life conditions, relevant for full-scale application. With the savings in wastewater discharge due to removal of organics, nitrogen and phosphorus as an important economic driver, priorities must go to using PPB-enriched cultures and real waste matrices. The costs associated with artificial illumination, followed by centrifugal harvesting/dewatering and drying, are estimated to be 1.9, 0.3-2.2 and 0.1-0.3 $·kgdry biomass-1. At present, these costs are likely to exceed revenues. Future research efforts must be carried out outdoors, using sunlight as energy source. The growth of bulk biomass on relatively clean wastewater streams (e.g. from food processing) and its utilization as a protein-rich feed (e.g. to replace fishmeal, 1.5-2.0 $·kg-1) appears as a promising valorisation route. | 10.1016/j.biotechadv.2020.107567 |
pubmed_800_23577 | This communication introduces a simple method to determine the pKs of microscopic ionizations from complex titration curves. We used this approach to study the alkaline transition (pH-dependent ligand exchange) of mitochondrial cytochrome c. The linearization of titration curves permitted resolution of two to three limiting microscopic ionizations. By combining these data with studies of the temperature dependence of ligand-exchange equilibria, we found evidence that the alkaline transition comprises two chemically distinct processes: the deprotonation of the alternative ligands and the break of the iron-methionine ligation bond. We also noted that, in the horse and untrimethylated S. cerevisiae iso-1 cytochromes c, the permissible deprotonation of the epsilon-amino group of Lys(72) allows formation of an alkaline isomer at lower pH, with lesser stability, which leads to hysteresis in the titration curves. The linearization of the titration curves for different cytochromes c thus brings insight on the microscopic contributions to conformational stability. | 10.1016/S0006-3495(01)75879-1 |
pubmed_421_24966 | OBJECTIVE
Diabetes is associated with poor oral health, but incremental expenditures for dental care associated with diabetes in the U.S. are unknown. We aimed to quantify these incremental expenditures per person and for the nation.
RESEARCH DESIGN AND METHODS
We analyzed data from 46,633 noninstitutionalized adults aged ≥18 years old who participated in the 2016-2017 Medical Expenditure Panel Survey. We used two-part models to estimate dental expenditures per person in total, by payment source, and by dental service type, controlling for sociodemographic characteristics, health status, and geographic variables. Incremental expenditure was the difference in predicted expenditure for dental care between adults with and without diabetes. The total expenditure for the U.S. was the expenditure per person multiplied by the estimated number of people with diabetes. Expenditures were adjusted to 2017 USD.
RESULTS
The mean adjusted annual diabetes-associated incremental dental expenditure was $77 per person and $1.9 billion for the nation. Of this incremental expenditure, 51% ($40) and 39% ($30) were paid out of pocket and by private insurance, 69% ($53) of the incremental expenditure was for restorative/prosthetic/surgical services, and adults with diabetes had lower expenditure for preventive services than those without (incremental, -$7). Incremental expenditures were higher in older adults, non-Hispanic Whites, and people with higher levels of income and education.
CONCLUSIONS
Diabetes is associated with higher dental expenditures. These results fill a gap in the estimates of total medical expenditures associated with diabetes in the U.S. and highlight the importance of preventive dental care among people with diabetes. | 10.2337/dc20-2744 |
pubmed_374_2739 | A high tibial osteotomy (HTO) that is used to correct varus malalignment, such as with medial arthrosis or before cartilage restoration or posterolateral reconstructions, represents an important and required surgery for clinical success. A major problem that occurs with HTO planning is that the preoperative measurements, with either lower limb supine or standing weight-bearing radiographs, will invariably show abnormal medial or lateral tibiofemoral compartment opening resulting from soft-tissue laxity or injury. It is imperative that this tibiofemoral joint opening be accounted for in the osteotomy correction calculations. There are well-described methods available that affect operative planning, such as the use of preoperative stress radiographs to determine the millimeters of tibiofemoral opening or closure. The use of intraoperative fluoroscopy with application of axial loading to the lower limb and verification of closure of the tibiofemoral joint is recommended. A careful fluoroscopic examination of the tibiofemoral compartments allows a final adjustment of the osteotomy correction and confirms the final weight-bearing line percent measurement and limb alignment. Postoperative radiographs are required to detect outliers resulting from unexpected soft-tissue laxity or inadequate correction. | 10.1016/j.arthro.2020.03.018 |
pubmed_83_10158 | Previous researches have indicated that sleep plays a vital role in cognitive functions. Sleep deprivation (SD) causes learning and memory damage, which is associated with oxidative stress. This study was performed to investigate the neuroprotective effects of an extract of Abelmoschus manihot flower (EAM) against memory deficit induced by SD in mice. The SD model was evoked by multiple platform method for 5 days, successively. The learning and memory-improving effects of EAM were assessed by behavioral trials and the underlying mechanism was investigated by measuring the oxidative stress alteration. Our findings indicated that the SD-induced memory deficit and the EAM treatment improved the cognitive functions of mice in the object location recognition test and passive avoidance task. In addition, EAM effectively improved the activities of the antioxidant enzyme, decreased the content of malondialdehyde (MDA), and restored the protein expression of the brain-derived neurotrophic factor (BDNF), tyrosine kinase B (TrkB) and glutamate receptor 1 (GluR1) in brain tissues. In conclusion, EAM could improve the SD-evoked learning and memory impairments. The possible underlying mechanisms of EAM may be related to its antioxidant capacity and enhanced BDNF/TrkB/GluR1 levels in the hippocampal memory. | 10.1039/d0fo02158j |
pubmed_176_14305 | PURPOSE
To detail the spectrum of eye manifestations in Takayasu arteritis and factors predisposing to its development.
METHODS
In this cross-sectional study, 61 patients with proven Takayasu arteritis who were identified during a 16-month period were evaluated for disease- and treatment-related eye manifestations. A fundus fluorescein angiography examination was performed where indicated and with the patients consent.
RESULTS
The mean (±standard deviation) duration of illness before ophthalmic evaluation was 55 ± 69 months. Decreased vision was the most common ocular symptom (30%). Thirty-five patients underwent fundus fluorescein angiography examination. Takayasu retinopathy was seen in 9 (15%), ocular ischemic syndrome in 4 (7%), and hypertensive retinopathy in 10 (16%) patients. The most common treatment-related ocular complication was steroid-induced cataract (23%). Other manifestations included iris neovascularization (n = 3), anterior ischemic optic neuropathy (n = 2), steroid-induced glaucoma (n = 1), neovascular glaucoma (n = 1), and uveitis (n = 1). Those manifesting Takayasu retinopathy and ocular ischemic syndrome had significantly (P < 0.05) lower blood pressure in both upper limbs compared with patients not manifesting ischemic retinopathy. A significant (P < 0.03) proportion of patients with Takayasu retinopathy and ocular ischemic syndrome had a nonrecordable right upper limb blood pressure.
CONCLUSION
Disease- and treatment-related ocular complications are not infrequent in Takayasu arteritis. Arteritis involving the aortic arch and its branches favors the development of ischemic ocular complications. | 10.1097/IAE.0b013e3181fe540b |
pubmed_186_9961 | The residence time of (210)Pb created in the atmosphere by the decay of gaseous (222)Rn is a key parameter controlling its distribution and fallout onto the landscape. These in turn are key parameters governing the use of this natural radionuclide for dating and interpreting environmental records stored in natural archives such as lake sediments. One of the principal methods for estimating the atmospheric residence time is through measurements of the activities of the daughter radionuclides (210)Bi and (210)Po, and in particular the (210)Bi/(210)Pb and (210)Po/(210)Pb activity ratios. Calculations used in early empirical studies assumed that these were governed by a simple series of equilibrium equations. This approach does however have two failings; it takes no account of the effect of global circulation on spatial variations in the activity ratios, and no allowance is made for the impact of transport processes across the tropopause. This paper presents a simple model for calculating the distributions of (210)Pb, (210)Bi and (210)Po at northern mid-latitudes (30°-65°N), a region containing almost all the available empirical data. By comparing modelled (210)Bi/(210)Pb activity ratios with empirical data a best estimate for the tropospheric residence time of around 10 days is obtained. This is significantly longer than earlier estimates of between 4 and 7 days. The process whereby (210)Pb is transported into the stratosphere when tropospheric concentrations are high and returned from it when they are low, significantly increases the effective residence time in the atmosphere as a whole. The effect of this is to significantly enhance the long range transport of (210)Pb from its source locations. The impact is illustrated by calculations showing the distribution of (210)Pb fallout versus longitude at northern mid-latitudes. | pubmed_186_9961 |
pubmed_183_10188 | STUDY OBJECTIVE
To analyze the pharmacokinetic properties of the immunosuppressants cyclosporine and tacrolimus when either is coadministered with oral posaconazole.
DESIGN
Two single-center, open-label pharmacokinetic studies of cyclosporine in a multiple-dose design and of tacrolimus in a one-sequence, crossover, single- and multiple-dose design.
SETTING
One clinical investigative center in the United States and one in the United Kingdom.
SUBJECTS
Four adult heart transplant recipients in the cyclosporine study and 36 healthy adult volunteers in the tacrolimus study.
INTERVENTIONS
In the cyclosporine study, patients who took an established cyclosporine dose 3 times/day for 6 weeks or longer were given posaconazole 200 mg/day for 10 days. In the tacrolimus study, subjects received tacrolimus 0.05 mg/kg/day on days 1 and 14 and posaconazole 400 mg twice/day on days 7-14.
MEASUREMENTS AND MAIN RESULTS
In the cyclosporine study, blood samples were collected on day 1 to determine cyclosporine pharmacokinetics and on day 10 to measure the pharmacokinetics of cyclosporine and posaconazole. Coadministration of posaconazole increased cyclosporine exposure and necessitated dosage reductions of 14-29% for cyclosporine in three subjects. In the tacrolimus study, blood samples were collected on days 12-14 to assess posaconazole pharmacokinetics and on days 1 and 14 for as long 72 hours after dosing to evaluate tacrolimus pharmacokinetics. Posaconazole increased the maximum blood concentration and the area under the concentration-time curve for tacrolimus by 121% and 358%, respectively, on day 14 compared with day 1 (both p=0.001). In both studies, posaconazole pharmacokinetics were unaffected.
CONCLUSION
These findings suggest that the dosage of cyclosporine or tacrolimus should be reduced when posaconazole therapy is started and that plasma levels of the immunosuppressant should be monitored during and at the discontinuation of posaconazole therapy so that dosages are adjusted accordingly. This recommendation is consistent with current standard of care for patients receiving cyclosporine or tacrolimus with concomitant azole antifungal therapy. | 10.1592/phco.27.6.825 |
pubmed_1058_20816 | The Autographa californica nuclear polyhedrosis virus da26 gene codes for an envelope protein of both budded virus (BV) and occlusion derived virus (ODV). Western blot and temporal analysis of infected cell extracts detected a protein of 26 kDa by 4 h postinfection (p.i.). The amount of protein increased by 16 h p.i. and remained at high levels throughout infection. By 36 h p.i. several additional immunoreactive proteins were detected which migrated at approximately 18 kDa and remained through 96 h p.i. Western blot analysis of purified virus envelope and nucleocapsid preparations revealed that both the 26- and 18-kDa proteins are structural proteins of the envelope of BV and ODV. Immunoelectron microscopy performed at a time when only the 26-kDa species of the protein was present confirmed that the protein located to ODV envelope. The protein was named BV/ODV-E26 to designate incorporation into viral progeny, envelope location, and apparent molecular weight. Studies designed to follow localization of BV/ODV-E26 demonstrated that early in infection, the protein was incorporated into cytoplasmic vesicles and by 16 h p.i., BV/ODV-E26 was detected in the nucleus associated with virus-induced intranuclear microvesicles and ODV envelope. Coimmunoprecipitation and yeast two-hybrid assays showed that BV/ODV-E26 and FP25K were capable of interacting with each other to form a complex and coimmunoprecipitation assays indicated that cellular actin was a third component of this complex. Together, these data suggest that FP25K and cellular actin may participate in the regulation, or movement through the cell, of baculovirus proteins and/or virus nucleocapsids. | 10.1006/viro.1997.8903 |
pubmed_790_387 | Two glucosamine (GCA)-requiring mutants have been isolated which grow on glucose minimal or nutrient sporulation medium only in the presence of either GCA or acetyl-GCA. They lack the l-glutamine-d-fructose-6-phosphate aminotransferase (EC 2.6.1.13), which is repressible by GCA and whose activity in the standard strain decreases after cessation of growth. But the mutants can grow on GCA as sole carbon and ammonia source, because GCA induces the synthesis of 2-amino-2-deoxy-d-glucose-6-phosphate ketol-isomerase (deaminating) (EC 5.3.1.10). With respect to sporulation, the GCA-requiring mutants are in a serious dilemma, as GCA represses the onset of massive sporulation and yet a small amount of GCA-6-phosphate derivatives is necessary to allow sporulation. When GCA is continuously provided in small quantities, sporelike particles are produced which contain little or no spore cortex but a normal spore coat. Apparently, GCA derivatives are needed especially for cortex formation. Many of the sporelike particles can produce colonies after octanol, but not after heat treatment. When they are purified by treatment with lysozyme and sodium dodecylsulfate, they do not show the decrease in optical density at 600 nm typical of germination nor do they produce offspring. | 10.1128/jb.101.3.1046-1062.1970 |
pubmed_584_14907 | While the p53 homologue p73 has been found to be involved in tumorigenesis, the molecular mechanisms involved in this function are still not fully evident. The presence of two distinct promoters allows the formation of two proteins with opposite effects: while TA-p73 shows pro-apoptotic effects, DeltaN-p73 has an evident anti-apoptotic function. The relative expression of the two proteins is in fact related to the prognosis of several cancers. Since both p73 and p63, the other member of the same family, share the ability to interact with each other, it is important to understand the mechanisms that control the degradation and stability of both proteins, and their relative isoforms. p73 and p63 stability is regulated not only by protein modifications (phosphorylation, acetylation) but also by its degradation in the proteasome. To this end, the interaction with Mdm2, p300/CBP, and SUMO-1 are discussed in details. | 10.1016/s0006-2952(03)00511-2 |
pubmed_83_5575 | Bioprinting is a rapidly developing technology for the precise design and manufacture of tissues in various biological systems or organs. Coaxial extrusion bioprinting, an emergent branch, has demonstrated a strong potential to enhance bioprinting's engineering versatility. Coaxial bioprinting assists in the fabrication of complex tissue constructs, by enabling concentric deposition of biomaterials. The fabricated tissue constructs started with simple, tubular vasculature but have been substantially developed to integrate complex cell composition and self-assembly, ECM patterning, controlled release, and multi-material gradient profiles. This review article begins with a brief overview of coaxial printing history, followed by an introduction of crucial engineering components. Afterward, we review the recent progress and untapped potential in each specific organ or biological system, and demonstrate how coaxial bioprinting facilitates the creation of tissue constructs. Ultimately, we conclude that this growing technology will contribute significantly to capabilities in the fields of in vitro modeling, pharmaceutical development, and clinical regenerative medicine. | 10.1016/j.bioactmat.2020.08.020 |
pubmed_178_9866 | It is current practice to only consider heart-beating donors as suitable for organ donation. Patients who have sustained a permanent cardiac arrest are believed to be unsuitable for kidney retrieval, in the knowledge that the kidneys will have received extensive ischemic damage. In situ kidney preservation (ISP), using the double balloon triple lumen (DBTL) catheter, offers the possibility of harvesting valuable kidneys from these, otherwise unsuitable, donors. With this technique human kidneys can be cooled in situ prior to the donor nephrectomy. During ISP, nephrectomy can be performed under optimal surgical conditions. In this report indications for ISP, insertion technique of the DBTL catheter, legal aspects, and transplantation outcome of kidneys harvested by means of ISP are discussed. | pubmed_178_9866 |
pubmed_689_7456 | The long-term cardiorespiratory function in burn-injured children can be jeopardized due to complications brought on by the injury. This study sought to assess the cardiorespiratory responses to maximal exercise in children who sustained a burn injury and explore the relationships among cardiorespiratory response, physical activity levels (PALs), and health-related quality of life (HRQL). Forty-five burn-injured children (age: 13.89 ± 2.43 years; duration since burn injury: 3.13 ± 0.93 years) and 52 age- and gender-matched healthy children (14.15 ± 2.27 years) participated in this study. Both cohorts were evaluated for the maximal exercise capacity (defined by peak oxygen uptake [VO2peak], maximum heart rate [HRmax], minute ventilation [VE], ventilatory equivalent [VEq], respiratory rate [RR], and respiratory exchange ratio [RER]), PALs, and HRQL. The burn-injured children had significantly lower VO2peak (P = .0001) and VE (P = .003) and higher VEq (P < .0001) and RR (P = .007) than their healthy controls, indicating less-efficient cardiorespiratory capacity. However, the HRmax (P = .092) and RER (P = .251) were similar. The burn-injured children reported significantly lower PALs (P = .014) and HRQL (P < .0001). The PALs (r [95% CI] = .411 [0.132-0.624]; P = .005) and HRQL (r [95% CI] = .536 [0.284-0.712]; P = .0001) were significantly correlated with the cardiorespiratory capacity represented by VO2peak in burn-injured group. The variations in VO2peak explained ~17% and 28.7% of the variations in PALs and HRQL, respectively. In conclusion, the cardiorespiratory efficiency of the burn-injured children may remain limited, even up to a few years following the injury. The limited cardiorespiratory capacity accounts in part for the reduced PALs and HRQL. | 10.1093/jbcr/irab203 |
pubmed_1022_13877 | BACKGROUND
Long-term laboratory monitoring is recommended after gastric bypass surgery to prevent the development of micronutrient deficiencies. The objective of this study was to characterize patterns of laboratory monitoring after surgery.
METHODS
We used a large insurance claims database to assess the frequency of laboratory testing after gastric bypass surgery. We assessed the tests recommended by an expert panel on bariatric surgery, including tests recommended routinely as well as second-line tests for specific clinical scenarios (e.g., tests for anemia when iron deficiency is not present).
RESULTS
With the exception of testing for diabetes, most gastric bypass patients did not undergo routine laboratory testing in the first year after their surgery, ranging from 54% (electrolytes) to 95% (zinc). However, for first-line tests, significantly more gastric bypass patients underwent testing in the first year,compared with gastric banding patients. Differences in testing frequency between gastric bypass and gastric banding patients were larger for tests of micronutrient deficiency than for common metabolic panels and complete blood counts. For second-line tests, much smaller percentages of both groups of patients underwent testing, either in the first year or after year 1.
CONCLUSION
Patients undergoing gastric bypass do not routinely undergo recommended laboratory tests, although they are undergoing more monitoring than gastric banding patients. Efforts must be made by patients, surgeons, and primary care providers to ensure that routine testing is done to lower the risk of adverse health outcomes. | pubmed_1022_13877 |
pubmed_653_6909 | Exploratory variability is essential for sensorimotor learning, but it is not known how and at what timescales it is regulated. We manipulated song learning in zebra finches to experimentally control the requirements for vocal exploration in different parts of their song. We first trained birds to perform a one-syllable song, and once they mastered it, we added a new syllable to the song model. Remarkably, when practicing the modified song, birds rapidly alternated between high and low acoustic variability to confine vocal exploration to the newly added syllable. Furthermore, even within syllables, acoustic variability changed independently across song elements that were only milliseconds apart. Analysis of the entire vocal output during learning revealed that the variability of each song element decreased as it approached the target, correlating with momentary local distance from the target and less so with the overall distance within a syllable. We conclude that vocal error is computed locally in subsyllabic timescales and that song elements can be learned and crystallized independently. Songbirds have dedicated brain circuitry for vocal babbling in the anterior forebrain pathway (AFP), which generates exploratory song patterns that drive premotor neurons at the song nucleus RA. We hypothesize that either AFP adjusts the gain of vocal exploration in fine timescales or that the sensitivity of RA premotor neurons to AFP/HVC inputs varies across song elements. | 10.1523/JNEUROSCI.3740-11.2012 |
pubmed_1092_16879 | Melatonin is neurohormone, which is involved in regulation of many functions of an organism, including the digestive system. Therefore the authors offered to include this hormone as a preconditioner factor in surgical treatment of colon tumors using laparotomy and laparoscopy. Preoperative application of melatonin allowed shortening the terms of postoperative period and hospital stay. | pubmed_1092_16879 |
pubmed_40_17220 | The aim of this study was to investigate the influence of impulse noise on age-related hearing loss. The study consisted of two groups. Each group contained 109 men. Group I comprised veterans with normal hearing at the end of 1979 sino-vietnamese war. All these veterans were randomly selected from Guangzhou Military Command. Group II were men with no military experience randomly chosen from the health examination center of Guangzhou General Hospital of Guangzhou Military Command. Pure-tone thresholds of these two groups were measured and compared. The pure-tone thresholds of Group I were poorer than those of Group II at the frequencies of 4, 6 and 8 kHz. Thus, impulse noise accelerates age-related hearing loss. | 10.1007/s00405-013-2622-x |
pubmed_229_21236 | Using microarray analysis, we identified a unique ras superfamily gene, termed RERG (ras-related and estrogen-regulated growth inhibitor), whose expression was decreased or lost in a significant percentage of primary human breast tumors that show a poor clinical prognosis. Importantly, high RERG expression correlated with expression of a set of genes that define a breast tumor subtype that is estrogen receptor-positive and associated with a slow rate of tumor cell proliferation and a favorable prognosis for these cancer patients. RERG mRNA expression was induced rapidly in MCF-7 cells stimulated by beta-estradiol and repressed by tamoxifen treatment. Like Ras, RERG protein exhibited intrinsic GDP/GTP binding and GTP hydrolysis activity. Unlike Ras proteins, RERG lacks a known recognition signal for COOH-terminal prenylation and was localized primarily in the cytoplasm. Expression of RERG protein in MCF-7 breast carcinoma cells resulted in a significant inhibition of both anchorage-dependent and anchorage-independent growth in vitro and inhibited tumor formation in nude mice. These features of RERG are strikingly different from most Ras superfamily GTP-binding pro-teins and suggest that the loss of RERG expression may contribute to breast tumorigenesis. | 10.1074/jbc.M105888200 |
pubmed_370_11361 | The absorbable synthetic suture (PDS suture 6-0 with spatula needle) was examined by experiments on the tendon of the M. flexor digitorum pedis communis of the hare. A total of 34 tendon sutures was prepared histologically and evaluated. The new suture material is distinguished by greatly extended absorption time, low foreign body reaction and an improved tensile strength. With this suture, the conditions in which absorbable suture material can be used are increased. This is particularly true of so-called bradytrophic tissue. | pubmed_370_11361 |
pubmed_1069_5291 | This study investigated the neural basis and cognitive mechanisms of disorders affecting the visual processing of human faces. Two patients affected by prosopagnosia (PA), 45 unilateral brain-damaged patients not previously selected for gnosic disturbance, and 52 normal subjects were administered three tasks involving visual matching of unfamiliar faces, identification of famous faces, and age attribution to unknown faces. Results confirmed that the right hemisphere (and particularly the posterior region) is critical for all of the main aspects of facial processing. Neuroradiological and PET examination in both PA patients revealed a lesion in the territory of the right posterior cerebral artery (infero-mesial areas of temporal and occipital lobes). Moreover, group comparisons showed that patients affected by a right posterior lesion obtained the worst scores on all tasks of our battery. Both group comparisons and single-case analyses pointed out that a deficient recognition of familiar faces is generally independent of perceptual disorders and, as such, should be considered mnestic in nature. Disorders in the age attribution, on the contrary, appear to be strictly associated with deficits in the perceptual analysis of unfamiliar faces. | 10.1080/01688639508405159 |
pubmed_675_23351 | The ε4 allele of the apolipoprotein E (APOE) gene is the strongest genetic risk factor for late-onset Alzheimer's disease (AD) and greatly influences the development of amyloid-β (Aβ) pathology. Our current study investigated the potential therapeutic effects of the anti-human APOE antibody HAE-4, which selectively recognizes human APOE that is co-deposited with Aβ in cerebral amyloid angiopathy (CAA) and parenchymal amyloid pathology. In addition, we tested whether HAE-4 provoked brain hemorrhages, a component of amyloid-related imaging abnormalities (ARIA). ARIA is an adverse effect secondary to treatment with anti-Aβ antibodies that can occur in blood vessels with CAA. We used 5XFAD mice expressing human APOE4 +/+ (5XE4) that have prominent CAA and parenchymal plaque pathology to assess the efficacy of HAE-4 compared to an Aβ antibody that removes parenchymal Aβ but increases ARIA in humans. In chronically treated 5XE4 mice, HAE-4 reduced Aβ deposition including CAA compared to a control antibody, whereas the anti-Aβ antibody had no effect on CAA. Furthermore, the anti-Aβ antibody exacerbated microhemorrhage severity, which highly correlated with reactive astrocytes surrounding CAA. In contrast, HAE-4 did not stimulate microhemorrhages and instead rescued CAA-induced cerebrovascular dysfunction in leptomeningeal arteries in vivo. HAE-4 not only reduced amyloid but also dampened reactive microglial, astrocytic, and proinflammatory-associated genes in the cortex. These results suggest that targeting APOE in the core of both CAA and plaques could ameliorate amyloid pathology while protecting cerebrovascular integrity and function. | 10.1126/scitranslmed.abd7522 |
pubmed_367_14541 | Gene expression profiling to analyze cellular responses against different stimuli or conditions is generally performed at the total cellular RNA level. This results in poor resolution of the temporal kinetics of the cellular response and a bias towards detecting up-regulation of short-lived transcripts. Furthermore, changes in transcription rate and RNA stability cannot be distinguished. These problems can be addressed by analyzing nascent RNA instead of total cellular RNA. Throughout the last few years methods have been developed for metabolic tagging and purification of nascent RNA. In this article, we review these experimental procedures and discuss their implications for large-scale gene expression profiling. | 10.1039/b911233b |
pubmed_448_835 | Considerable efforts have been made on the development of lipid nanoparticles (LNPs) for delivering of nucleic acids in LNP-based medicines, including a first-ever short interfering RNA (siRNA) medicine, Onpattro, and the mRNA vaccines against the coronavirus disease 2019 (COVID-19), which have been approved and are currently in use worldwide. The successful rational design of ionizable cationic lipids was a major breakthrough that dramatically increased delivery efficiency in this field. The LNPs would be expected to be useful as a platform technology for the delivery of various therapeutic modalities for genome editing and even for undiscovered therapeutic mechanisms. In this review, the current progress of my research, including the molecular design of pH-sensitive cationic lipids, their applications for various tissues and cell types, and for delivering various macromolecules, including siRNA, antisense oligonucleotide, mRNA, and the clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) system will be described. Mechanistic studies regarding relationships between the physicochemical properties of LNPs, drug delivery, and biosafety are also summarized. Furthermore, current issues that need to be addressed for next generation drug delivery systems are discussed. | 10.1248/cpb.c21-00705 |
pubmed_349_4795 | OBJECTIVES
Our goal was to compare the rates of in-hospital and 30-day major adverse cardiac and cerebrovascular events (MACCE) including death, stroke, myocardial infarction and repeat revascularization in patients with multivessel disease undergoing multiarterial (MultArt) coronary artery bypass grafting (CABG) with the left internal mammary artery/saphenous vein (LIMA/SV) CABG or percutaneous coronary intervention (PCI).
METHODS
From 1 January 1993 to 31 December 2009, 12 615 consecutive patients underwent isolated primary CABG (n = 6667) with LIMA/SV (n = 5712) or MultArt (n = 955) or were treated by PCI (n = 5948) with balloon angioplasty (n = 1020), bare metal stent (n = 3242), and drug-eluting stent (n = 1686). We excluded patients with acute myocardial infarction. We matched the CABG group with the 3 PCI subgroups, and the PCI group with the 2 CABG subgroups. Multivariable analyses were used to evaluate the impact of CABG versus PCI and their subgroups on early MACCE.
RESULTS
Unadjusted early MACCE were lower for MultArt (1.5%) than for LIMA/SV (4.5%, P < 0.001) and PCI (8.5%, P < 0.001). In matched analysis, CABG had lower early MACCE versus balloon angioplasty (4.7% vs 13.2%, P < 0.001), bare metal stent (4.3% vs 8.3%, P < 0.001), and drug-eluting stent (2.9% vs 5.5%, P = 0.008), as well as LIMA/SV versus PCI (4.6% vs 9.2%, P < 0.001) and MultArt versus PCI (1.8% vs 7.8%, P < 0.001). Stroke rate was similar in MultArt versus PCI (0.8% vs 0.3%, P = 0.18) but higher with LIMA/SV versus PCI (2.3% vs 0.4%, P < 0.001). In multivariable analysis, PCI (odds ratio 4.53, 95% confidence interval: 2.62-7.83; P < 0.001) and LIMA/SV (odds ratio 2.04, 95% confidence interval: 1.18-3.53; P < 0.011) were strong predictors of early MACCE compared with MultArt.
CONCLUSIONS
MultArt confers the lowest rate of early MACCE. | 10.1093/ejcts/ezx171 |
pubmed_152_16014 | PURPOSE OF REVIEW
Venom immunotherapy has proven to be a very effective method for the prevention of future re-sting reactions. However, initiation of the venom injection program is just the beginning. This review looks at recent papers which shed light on other issues that arise during maintenance venom immunotherapy.
RECENT FINDINGS
Prophylactic antihistamines taken before venom injections reduce the frequency of reactions and one report suggests that they may improve efficacy. The schedule of venom injections usually does not have to be adjusted for patients who develop local reactions; a very large reaction may be the exception. Patients who react to stings should have their maintenance doses increased. Most patients are able to extend the interval between injections to 8 weeks in the third year of treatment. Two groups have proposed a maintenance interval of 12 weeks for routine use.
SUMMARY
Our understanding of insect sting sensitivity continues to improve, leading to better outcomes for allergic patients. | 10.1097/00130832-200208000-00011 |
pubmed_468_22643 | RecA is a highly conserved bacterial protein that plays crucial roles in many cellular processes and hence is a potential target in the chemotherapy of bacterial infections. An understanding of the functional similarity between RecA proteins from different bacterial species should yield further insights into the biochemistry of RecA protein, along with the potential for new approaches to facilitate the improvement of RecA-targeted drugs. In this technical note, the authors present an in silico method based on tri-oligonucleotide usage correlations (TOUC) to predict the functional similarity between two RecA orthologs. The TOUC values analyzed in this study are in good agreement with the available experimental results. This method should prove useful in guiding future experimental efforts aimed at furthering our understanding of the biochemistry of RecA proteins and subsequent development of new drugs that modulate RecA biological activities in bacteria. | 10.1177/1087057111400909 |
pubmed_324_10578 | Phylogenetic inference based on language is a vital tool for tracing the dynamics of human population expansions. The timescale of agriculture-based expansions around the world provides an informative amount of linguistic change ideal for reconstructing phylogeographies. Here we investigate the expansion of Arawak, one of the most widely dispersed language families in the Americas, scattered from the Antilles to Argentina. It has been suggested that Northwest Amazonia is the Arawak homeland based on the large number of diverse languages in the region. We generate language trees by coding cognates of basic vocabulary words for 60 Arawak languages and dialects to estimate the phylogenetic relationships among Arawak societies, while simultaneously implementing a relaxed random walk model to infer phylogeographic history. Estimates of the Arawak homeland exclude Northwest Amazonia and are bi-modal, with one potential homeland on the Atlantic seaboard and another more likely origin in Western Amazonia. Bayesian phylogeography better supports a Western Amazonian origin, and consequent dispersal to the Caribbean and across the lowlands. Importantly, the Arawak expansion carried with it not only language but also a number of cultural traits that contrast Arawak societies with other lowland cultures. | 10.1098/rspb.2010.2579 |
pubmed_165_5149 | Invasive pulmonary aspergillosis is acquired through inhalation of conidia. Little is known about early interactions between Aspergillus fumigatus conidia and alveolar epithelial cells, so an in vitro model was developed to study binding between conidia and A549 cells, a line of type II pneumocytes. Conidia rapidly became attached to confluent monolayers of A549 cells in serum-free medium, reaching a plateau within 40 min. Scanning electron microscopy (EM) showed a random pattern of early adherence; viable conidia subsequently became clustered on pneumocyte surfaces. Following germination of pneumocyte-adherent conidia for 12 h, direct penetration of epithelial cells by hyphae could be demonstrated by scanning and transmission EM. These data suggest that an early event following inhalation of A. fumigatus conidia may be binding of conidia to pneumocytes, followed by hyphal penetration of the epithelial cell layer. | 10.1093/infdis/175.1.146 |
pubmed_386_19854 | OBJECTIVES
Poor weight gain during the first weeks of life in preterm infants is closely associated with the risk of developing the retinopathy of prematurity (ROP) and insufficient nutrition might be an important contributing factor. This study aimed to evaluate the effect of energy and macronutrient intakes during the first 4 weeks of life on the risk for severe ROP (stages 3-5).
STUDY DESIGN
A population-based study including all Swedish extremely preterm infants born before 27 gestational weeks during a 3-year period. Each infant was classified according to the maximum stage of ROP in either eye as assessed prospectively until full retinal vascularisation. The detailed daily data of actual intakes of enteral and parenteral nutrition and growth data were obtained from hospital records.
RESULTS
Of the included 498 infants, 172 (34.5%) had severe ROP and 96 (19.3%) were treated. Energy and macronutrient intakes were less than recommended and the infants showed severe postnatal growth failure. Higher intakes of energy, fat and carbohydrates, but not protein, were significantly associated with a lower risk of severe ROP. Adjusting for morbidity, an increased energy intake of 10 kcal/kg/day was associated with a 24% decrease in severe ROP.
CONCLUSIONS
We showed that low energy intake during the first 4 weeks of life was an independent risk factor for severe ROP. This implies that the provision of adequate energy from parenteral and enteral sources during the first 4 weeks of life may be an effective method for reducing the risk of severe ROP in extremely preterm infants. | 10.1136/archdischild-2014-306816 |
pubmed_200_13798 | Metazoan transcriptional repressors regulate chromatin through diverse histone modifications. Contributions of individual factors to the chromatin landscape in development is difficult to establish, as global surveys reflect multiple changes in regulators. Therefore, we studied the conserved Hairy/Enhancer of Split family repressor Hairy, analyzing histone marks and gene expression in Drosophila embryos. This long-range repressor mediates histone acetylation and methylation in large blocks, with highly context-specific effects on target genes. Most strikingly, Hairy exhibits biochemical activity on many loci that are uncoupled to changes in gene expression. Rather than representing inert binding sites, as suggested for many eukaryotic factors, many regions are targeted errantly by Hairy to modify the chromatin landscape. Our findings emphasize that identification of active cis-regulatory elements must extend beyond the survey of prototypical chromatin marks. We speculate that this errant activity may provide a path for creation of new regulatory elements, facilitating the evolution of novel transcriptional circuits. | 10.7554/eLife.06394 |
pubmed_715_8669 | Ovulation failure and double ovulation rates were examined in 1917 inseminations performed in high-yielding dairy cows under standard commercial conditions. The ovulation rate was determined 11 days post-insemination by ultrasound detection of at least one corpus luteum in the ovaries. Analyzing the double ovulation and pregnancy rates, the study population consisted only of ovulated cows (n = 1792). Data were analyzed using logistic regression methods. A failure to ovulate was recorded in 125/1917 (6.5%) services: 82/663 (12.4%) during the warm and 43/1254 (3.4%) during the cool period. Based on the odds ratios, the risk of ovulation failure was 3.9 times higher for inseminations performed during the warm period. No significant effects of estrous synchronization, milk production and days in milk at AI, and service and lactation number on ovulation failure were found. Double ovulation was recorded in 277/1792 (15.5%) services: 146 (52.7%) unilateral double ovulations (42.5% left versus 57.5% right); 115 (41.5%) bilateral double ovulations; and 16 (5.8%) triple ovulations. Double ovulation was recorded in 72 (12.4%) and 205 (16.9%) AI during the warm and the cool period, respectively. The percentages of double ovulation for first, second and third or more lactations were 6.7, 16.6 and 25%, respectively. Double ovulation rates for early (less than 90 days), mid- (90-150 days) and late (more than 150 days) lactation periods were 13, 20.7 and 14.2%, respectively. Reaching estrus during the warm period decreased the likelihood of double ovulation by a factor of 0.86; the risk of double ovulation was lower in cows with higher milk production (a 1 kg increase in milk yield led to a 0.97-fold reduced risk of double ovulation); cows in their second and in their third or more lactations showed a likelihood of double ovulation (using the first lactation as reference) increased by factors of 3.4 and 5.6, respectively; and reaching estrus during the early and late lactation period was related to a decreased probability of double ovulation (using the mid-lactation period as reference) by factors of 0.56 and 0.84, respectively. No significant effects of synchronization and service number on the double ovulation rate were found. Pregnancy was recorded in 914/1792 (51%) services: rates of 53.5% (811/1515) were recorded for single ovulations; 37.2% (103/277) for double ovulations: 28.8% (42/146) for unilateral double ovulations; 45.2% (52/115) for bilateral double ovulations; and 56.3% (9/16) for triple ovulations. The likelihood of pregnancy diminished in cows: inseminated during the warm period (by a factor of 0.5); inseminated by one particular bull (by a factor of 0.33); with higher milk production (a 1 kg increase in milk yield decreased the probability of pregnancy by a factor of 0.98); or undergoing unilateral (by a factor of 0.31) and bilateral (by a factor of 0.64) double ovulation. Logistic regression analysis indicated no significant effects of synchronization, days in milk, lactation number and service number on pregnancy rate. Collectively, our results indicate that cows showing estrus in conditions of heat stress had a high risk of ovulation failure. The effect of milk production on double ovulation was negative, whereas lactation number was positively correlated with this factor; the highest incidence of double ovulation occurring during the mid-lactation period. | 10.1016/j.theriogenology.2004.06.010 |
pubmed_573_4235 | Cell therapy is a major discipline of regenerative medicine that has been continually growing over the last two decades. The aging of the population necessitates discovery of therapeutic innovations to combat debilitating disorders, such as stroke. Menstrual blood and Sertoli cells are two gender-specific sources of viable transplantable cells for stroke therapy. The use of autologous cells for the subacute phase of stroke offers practical clinical application. Menstrual blood cells are readily available, display proliferative capacity, pluripotency and angiogenic features, and, following transplantation in stroke models, have the ability to migrate to the infarct site, regulate the inflammatory response, secrete neurotrophic factors, and have the possibility to differentiate into neural lineage. Similarly, the testis-derived Sertoli cells secrete many growth and trophic factors, are highly immunosuppressive, and exert neuroprotective effects in animal models of neurological disorders. We highlight the practicality of experimental and clinical application of menstrual blood cells and Sertoli cells to treat stroke, from cell isolation and cryopreservation to administration. | 10.2174/1871527311312030013 |
pubmed_1012_8104 | A fluorescence assay method for beta1-4galactosyltransferase (beta1-4GT) has been developed involving a pyridylaminated sugar as an acceptor substrate, a fluorescent sugar chain, with the reducing end of the Gnbeta1 - 2Malpha1 - 6(Gnbeta1-2Malpha1-3)Mbeta1 - 4Gnbeta1 - 4Gn - PA aminated with 2-aminopyridine. Microsome was prepared from the liver of normal male rats as an enzyme sample. Then the fluorescent reaction product was separated by reverse-phase HPLC. The kinetic experiments were carried out using crude enzyme extracts of the Golgi complex from the rat liver. The enzyme has a pH optimum of 6.5,and optimal concentration of Triton X-100 of 0.5%. The K(m) and V(max) values for the sugar acceptor substrates were found to be 2.31x10(-3)M(-1) and 5.75x10(-2) &mgr;mol/(min.mg) respectively. Furthermore, our research revealed that beta1-4GT had branch specificity. The Gn of alpha1-3 mannose branch of the acceptor substrate was more susceptible to galactosylation than that of the alpha1-6 branch by 2.10 times. | pubmed_1012_8104 |
pubmed_1056_904 | The inbred and congenic strain distribution of the I(H)-peptide marker in the variable region of mouse immunoglobulin light chains has been compared with other known genetic markers. A positive correlation was noted between the I(H)-peptide marker and expression of the Ly-3.1 thymocyte cell surface antigen. This suggests that the locus responsible for I(H)-peptide expression is genetically linked to the Ly-2 and Ly-3 loci in linkage group XI on chromsome 6 of the mouse. | 10.1084/jem.140.5.1432 |
pubmed_115_3894 | Kefir is a fermented beverage originating form the Caucasian regions composed of a number of bacteria and yeasts living together in polysaccharide grains secreted by them. Kefir can be considered a probiotic source as it presents anti-bacterial, anti-mycotic, anti-neoplasic and immunomodulatory properties. Aiming to appraise a possible anti-inflammatory effect of kefir we conducted cotton-induced granuloma and paw oedema assays in rats, the latter using carrageenan, dextran and histamine as stimuli. Kefir samples were thawed and continuously cultured during 15 days both in a molasses solution (50 g/l) and in cow's milk. A polysaccharide extract isolated from the grains (kefiran) was also tested in cotton-pellet experiments. The results showed significant inhibition in the formation of granuloma tissue for all the test groups, as compared to the blank group. Kefir suspensions in molasses presented an inhibition of 41 +/- 3% for the inflammatory process, fermented milk prepared from kefir showed 44 +/- 6% inhibition and kefiran extract 34 +/- 15%. Rat paw oedema also showed significant decreases with the mediators. Dextran-induced oedema was completely inhibited at 1 h after input, with a 76% inhibition after 2 h. Carrageenan stimulus was inhibited 62% after the 3rd hour, and histamine by 52% after the 2nd hour. These results points to the existence of anti-inflammatory prebiotic compounds present in symbiotic cultures of kefir growing in both aqueous and milky suspensions. | 10.1163/156856005774649395 |
pubmed_814_2138 | Currently, dementia is the only leading cause of death that is still on the rise, with total costs already exceeding those of cancer and heart disease and projected to increase even further in the coming years. Unfortunately, there are no satisfactory treatments and attempts to develop novel, more effective treatments have been extremely costly, albeit unsuccessful thus far. This has led us to investigate the use of established drugs, licensed for other therapeutic indications, for their potential application in cognitive disorders. This strategy, referred to as "drug repositioning," has been successful in many other areas including cancer and cardiovascular diseases. To our knowledge, this is the first study to investigate the effects of long-term treatment with verapamil, a calcium channel blocker commonly prescribed for various cardiovascular conditions and recently applied for prevention of cluster headaches, on the development of cognitive impairment in aged animals. Verapamil was studied at a low dose (1mg/kg/d) in a mouse model of sporadic Alzheimer's disease (sAD). Oral treatment with verapamil or vehicle was started, 24 h post-intracerebroventricular (ICV) streptozotocin/(STZ), in 12-month-old animals and continued for 3 months. Cognitive function was assessed using established tests for spatial learning, short-term/working memory, and long-term/reference memory. Our findings demonstrate that long-term low-dose verapamil effectively prevents development of ICV/STZ-induced cognitive impairment. It mitigates the astrogliosis and synaptic toxicity otherwise induced by ICV/STZ in the hippocampus of aged animals. These findings indicate that long-term, low-dose verapamil may delay progression of sAD in susceptible subjects of advanced age. | 10.1007/s12035-021-02350-9 |
pubmed_368_23424 | OBJECTIVES
The purpose of this study was to use spectral and cepstral analyses of speech to investigate whether underlying physiological changes in voice result in changes in acoustic estimates of dysphonia severity in continuous speech contexts within a single breath group. The effect of dysphonia on acoustic estimates of dysphonia severity, frequency, relative intensity, and vocalization time across initial and terminal segments of a single breath group using a common clinical stimulus was investigated.
STUDY DESIGN
Prospective quasi-experimental controlled design.
METHODS
Digitized recordings of the Consensus Auditory-Perceptual Evaluation of Voice sentence "We were away a year ago" were obtained from 20 treatment-seeking dysphonic individuals (females, mean age = 39 years) and 20 normal controls (females, mean age = 39 years). Each recorded sample was separated into the first four syllables ("We were away … ") and second four syllables ("…a year ago.") of the breath group. Cepstral and spectral measures, intensity measures, and temporal analyses were obtained and used in calculations of the Cepstral Spectral Index of Dysphonia (CSID, an acoustic estimate of dysphonia severity), fundamental frequency (F0), vocalization time, and relative vocal intensity (dB SLP). Statistical analyses were applied to calculations of change (delta [Δ]) in these measures from one breath group segment to the next.
RESULTS
Results revealed a significant effect of group on measures of CSID and F0, but not relative intensity or vocalization time. Dysphonic speakers exhibited a significant increase in the CSID from the first to second breath group segment and limited variation in F0 compared with controls.
CONCLUSIONS
These results may support the hypothesis that voice impairment increases in severity toward the termination of a breath group even within a short temporal frame (i.e., 2 seconds or less of connected speech), and that this portion of the breath group may be an important determinant of perceptual impressions. Further interpretation in the context of laryngeal physiology and indications for additional study will be discussed. | pubmed_368_23424 |
pubmed_810_13226 | BACKGROUND AND PURPOSE
We aimed to underline the importance of serum S100B protein as a useful biochemical marker in patients with obstructive sleep apnea syndrome (OSAS).
MATERIAL AND METHODS
Forty-three newly diagnosed patients with OSAS (median apnea-hypopnea index [AHI, events/ hour]: 37.5 [range 11.3-137]) and 25 subjects with AHI < 5 (median AHI: 4.4 [range 0.7-4.8]) were included in the study. Serum S100B protein level was tested in serum samples taken after polysomnography in both groups and the difference between OSAS patients and the control group regarding that level was assessed. In addition, the association of S100B protein serum level with age, body mass index, AHI, mean O2 saturation percentage during sleep, minimum O2 saturation value (%) at the end of the apneas, and the time spent at an O2 saturation less than 90% were analyzed in the OSAS patient group.
RESULTS
Median serum S100B protein level was 133.7 pg/ mL (range 20.97-230.70 pg/mL) in patients with OSAS and 16.1 pg/mL (range 10.1-22.9 pg/mL) in the control group (p < 0.005). Serum S100B protein level did not correlate with any studied variable (p > 0.05 for each correlation coefficient).
CONCLUSIONS
Serum S100B protein level is increased in patients with OSAS and may be a useful biochemical marker in those patients. | 10.5114/ninp.2012.31355 |
pubmed_91_1329 | Normal mouse sera were tested for cytotoxic antibody to surface antigens of cultured monolayer cells infected with AKR-derived ecotropic MuLV, xentropic MuLV, or dualtropic MCF 247 MuLV. Antibody to ecotropic MuLV-infected cells was found in a proportion of C57BL/6, C3Hf/Bi, AKR-Fv-1b, and (C3Hf/Bi X AKR)F1 mice, but not AKR or (AKR X C3Hf/Bi)F1 mice. Antibody to xenotropic MuLV-infected cells was virtually restricted to C57BL/6 mice. Antibody to MCF 247-infected cells was found in all strains tested, including AKR mice. Absorption analysis of (C3Hf/Bi x akr)f1 and AKR-Fv-1b sera with selective reactivity for MCF 247-infected cells showed that these sera recognize distinctive antigens on MCF 247-infected cells that are not present on ecotropic or xenotropic MuLV-infected cells. The transplantable AKR spontaneous leukemia AKSL2 was found to be uniquely sensitive to the cytotoxic action of naturally occurring antibody to MCF 247-related antigens and absorption tests with AKSL2 as the target cell and sera from a single AKR-Fv-1b mouse have permitted the definition of a new MuLV-related cell surface antigen, which has been designated G(AKSL2). Thymocytes from young mice of high leukemia-incidence strains (AKR, C58, and PL) express G(AKSL2), whereas thymocytes from 12 other strains do not. In AKR mice, the antigen is expressed in higher amounts on cells from thymus and bone marrow than on spleen cells. All AKR spontaneous leukemias tested express G(AKSL2), as did three MuLV-induced leukemias arising in G(AKSL2)- strains. Five X-ray-induced leukemias of G(AKSL2)- strains were G(AKSL2)-, as were MuLV+ and MuLV- chemically induced sarcomas. In the limited survey conducted to date, natural antibody to G(AKSL2) has been restricted to strains expressing G(AKSL2) in their normal tissues: AKR, AKR congenic mice AKR-Fv-1b and AKR hybrid mice (C3Hf/Bi x akr)f1 and (C57BL/6 X AKR)F1. In vitro G(AKSL2) induction tests involving MuLV infection of cultured monolayer cells showed that 8 of 12 newly isolated dualtropic MuLV shared the property of G(AKSL2) induction with the prototype MCF MuLV, MCF 247. Of the 12 ecotropic MuLV tested, only the N-tropic MuLV isolated from a leukemia originally induced by Passage A Gross virus induced G(AKSL2). The xenotropic and amphotropic MuLV isolates tested lacked G(AKSL2) inducing activity. Recognition of the g(aksl2) system provides a way to trace the origin and natural history of a class of dualtropic MCF MuLV in the mouse and to determine whether natural antibody to G(AKSL2) plays a role in AKR leukemogenesis. | 10.1084/jem.149.1.200 |
pubmed_716_18429 | d-Arabitol is a top value-added compound with wide applications in the food, pharmaceutical and biochemical industries. Nevertheless, sustainable biosynthesis of d-arabitol is limited by lack of efficient strains and suitable fermentation process. Herein, metabolic engineering and process optimization were performed in Zygosaccharomyces rouxii to overcoming these limitations. Adopting systems metabolic engineering include enhancement of innate biosynthetic pathway, supply of precursor substrate d-ribulose-5P and cofactors regeneration, a novel recombinant strain ZR-5A with good performance was obtained, which boosted d-arabitol production up to 29.01 g/L, 59.31 % higher than the parent strain. Further with the optimum medium composition and fed-batch fermentation, the strain ZR-5A finally produced 149.10 g/L d-arabitol with the productivity of 1.04 g/L/h, which was the highest titer ever reported by Z.rouxii system. This is the first report on the use of metabolic engineering to construct Z. rouxii chassis for the sustainable production of d-arabitol. | 10.1016/j.biortech.2022.128251 |
pubmed_776_11206 | Contemporary patterns of allele frequencies allow inferences on past evolutionary processes. L.L. CavalliSforza [(1988) Munibe 6, 129-137] and C. Renfrew [(1991) Cambridge Archaeol. J. 1, 3-23] proposed that neolithic farmers from the Near East propagated a group of related ancestral languages, from which three or four linguistic families developed. Here we show that genetic variation among Indo-European, Elamo-Dravidian, and Altaic speakers (grouped by some linguists in the Nostratic macrofamily) supports this hypothesis, whereas the evidence on Afro-Asiatic speakers is ambiguous. Gene-frequency clines within these linguistic families suggest that language diffusion was largely associated with population movements rather than with purely cultural transmission. Archeological, linguistic, and genetic evidence can be reconciled by envisaging a process of population growth and multidirectional dispersal from the Near East as the main factor shaping genetic and linguistic diversity in Eurasia and perhaps in North Africa. | 10.1073/pnas.90.10.4670 |
pubmed_93_4811 | CONTEXT
Nutrition education aims to enhance knowledge and improve dietary intake in athletes. Understanding athletes' nutrition knowledge and its influence on dietary intake will inform nutrition-education programs in this population.
PURPOSE
To systematically review the level of nutrition knowledge in athletes, benchmark this against nonathlete comparison groups, and determine the impact of nutrition knowledge on dietary intake.
METHODS
An extensive literature search from the earliest record to March 2010 using the terms nutrition knowledge or diet knowledge and athlete or sport was conducted. Included studies recruited able or physically disabled, male or female, competitive (recreational or elite) athletes over the age of 13 yr. Quantitative assessment of knowledge and, if available, diet intake was required. Because of variability in the assessment of nutrition knowledge and dietary intake, meta-analysis was not conducted.
RESULTS
Twenty-nine studies (17 published before 2000) measuring nutrition knowledge (7 including a nonathlete comparison group) met inclusion criteria. Athletes' knowledge was equal to or better than that of nonathletes but lower than comparison groups including nutrition students. When found statistically significant, knowledge was greater in females than males. A weak (r < .44), positive association between knowledge and dietary intake was reported in 5 of 9 studies assessing this. Common flaws in articles included inadequate statistical reporting, instrument validation, and benchmarking.
CONCLUSION
The nutrition knowledge of athletes and its impact on their dietary intake is equivocal. There is a need for high-quality, contemporary research using validated tools to measure nutrition knowledge and its impact on dietary intake. | 10.1123/ijsnem.21.3.248 |
pubmed_317_25183 | BACKGROUND
Forensic odontology nowadays has become a developing science and is of great importance to society. It is important that dental practitioners should have a proper knowledge of forensics as the need has increased greatly over the last decades due to the unprecedented demand from the criminal justice including terrorism in Kashmir valley (J&K India).
MATERIALS AND METHODS
Data was collected based on questionnaire survey among qualified dental practitioners related to their awareness of forensic odontology.
RESULTS
A total number of 235 dental practitioners responded to the questionnaire. RESULTS showed that there was a low confidence, in handling of forensic odontology related cases among dental practitioners and majority of dental practitioners were not having any formal training in forensic odontology.
CONCLUSION
Each dental practitioner has a responsibility to understand the forensic implications associated with the practice of his profession and thus he should work sincerely enough so to ensure his contribution in the field of forensic odontology. | 10.7860/JCDR/2014/9976.5273 |
pubmed_698_2494 | Microchimerism has been defined by the presence of a low number of circulating cells transferred from one individual to another. This transfer takes place naturally during pregnancy, between mother and fetus, or between fetuses in multigestational pregnancies. Furthermore, the establishment of microchimerism can also occur during blood transfusion, as well as during bone marrow and solid-organ transplants. Recently, microchimeric cells have been implicated in the pathogenesis of autoimmune diseases, particularly systemic sclerosis. Studies have demonstrated an increased presence of microchimeric cells in peripheral blood and tissues from patients with systemic sclerosis, and, more recently, microchimeric cells were demonstrated to be specifically activated and capable of recognizing patient human leukocyte antigens. | 10.1007/s11926-003-0044-2 |
pubmed_799_5299 | The aim of this study was to evaluate the effect of ultrasonic treatment on occlusion of dentine tubules in root canal walls after post space preparation in endodontically treated teeth. Twenty-four premolars were instrumented and filled using warm vertical condensation; after post space preparation, they were divided into two groups. The control group was treated using the etching procedure. The experiment samples were treated with EDTA irrigation and ultrasound activation for 30 s before the etching procedure. The roots were divided and the canal walls were examined under SEM at 1000x magnification. The debris and open tubule marks were observed at 2, 6, and 10 mm levels using a three-step scale and the differences in marks among the groups were tested for statistical significance. The following were observed: (a) A decrease in debris and open tubule marks in the samples treated with ultrasounds and the control group (p < 0.05), (b) no significant differences between the three levels of post space in debris and open tubule marks in the experiment samples, and (c) significant differences between the apical and coronal levels in debris and open tubule marks in the control group. | 10.1016/j.joen.2005.07.003 |
pubmed_1105_3113 | Negative-ion electrospray tandem mass spectrometry (ES-MS/MS) with collision-induced dissociation (CID) is attempted for sequence determination of alginate oligosaccharides, derived from polyanionic alginic acid, polymannuronate, and polyguluronate by partial depolymerization using either alginate lyase or mild acid hydrolysis. Sixteen homo- and hetero-oligomeric fragments were obtained after fractionation by gel-filtration and strong anion exchange high performance liquid chromatography. The product-ion spectra of these alginate oligosaccharides were dominated by intense B-, C-, Y-, and Z-type ions together with (0,2)A- and (2,5)A-ions of lower intensities. Internal mannuronate residues (M) produce weak but specific decarboxylated Z(int)-ions (Z(int) - 44 Da; int: denotes internal), which can be used for distinction of M and a guluronate residue (G) at an internal position. A reducing terminal M or G, although neither gives rise to a specific ion, can be identified by differences in the intensity ratio of fragment ions of the reducing terminal residue [(2,5)A(red)]/[(0,4)A(red)] (red: denotes reducing terminal). | 10.1016/j.jasms.2006.01.002 |
pubmed_71_24395 | BACKGROUND
Outcomes for children with acute myeloid leukemia (AML) have improved over the past 20 years even though the medications used for induction therapy have not changed.
METHODS
This study analyzed data from patients with AML who were enrolled in successive protocols (AML97 and AML02) to determine the contributors to the improved outcomes of the latter clinical trial.
RESULTS
There were significant improvements in 5-year overall survival (48.9% vs 71.2%; P < .0001) and event-free survival (43.5% vs 61.8%; P = .002) from AML97 to AML02. The 5-year cumulative incidence of early death (ED)/treatment-related mortality (TRM) was reduced for patients treated in AML02 (18.5% vs 7.9%; P = .007). Although the overall incidence of refractory disease (6.5% vs 5.6%; P = .736) and relapse (29.3% vs 21.0%; P = .12) did not differ between the 2 studies, patients with low-risk AML who were treated in AML02 had a reduced incidence of relapse (27.3% vs 8.8%; P = .036).
CONCLUSIONS
The improved outcomes of the AML02 trial resulted from improved disease control for low-risk patients and overall decreased ED/TRM. These results emphasize the importance of supportive-care measures throughout chemotherapy courses and hematopoietic cell transplantation and the value of treatment intensity for patients with low-risk AML while underscoring the need for novel therapy, rather than increased therapy intensity, for children with high-risk AML. Cancer 2017;123:3791-3798. © 2017 American Cancer Society. | 10.1002/cncr.30791 |
pubmed_1063_13840 | Polyaniline (PANI)/graphene oxide (GO) composites were synthesized via in situ polymerization of aniline in the presence of GO. The effect of microwave treatment of graphite on the electrical conductivity and electrochemical properties of PANI/GO composites was highlighted, and the morphology and microstructure were subsequently characterized using transmission electron microscopy, scanning electron microscopy, Fourier-transformed infrared spectroscopy, X-ray diffraction, and thermogravimetric analysis. The results demonstrated that microwave treatment of graphite imparted a well-dispersed, highly ordered layered structure to the as-prepared GO, and in turn facilitated strong bonding between the GO and PANI nanosheets, which may be responsible for the improved electrical conductivity and electrochemical properties of the resulting PANI/GO composites. The desired PANI/GO composites possessed an electrical conductivity of 508 S/m, an areal capacitance of 172.8 mF/cm², and a retained capacitance of 87.4% after cycling, representing percentage increases of 102, 232, and 112, respectively, as a result of the microwave treatment of graphite. The resulting composites are promising electrode materials for high-performance and ecofriendly electrical energy storage devices. | 10.3390/polym8110399 |
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