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pubmed_572_10888
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Acinetobacter baumannii is one of the most important nosocomial opportunistic pathogen worldwide. In addition, obesity has been associated with an increased risk of nosocomial infection, suggesting that there may be an association between A. baumannii and white adipose tissue. However, the effects of A. baumannii on adipocytes have not been well studied at the molecular level. Here, we investigated the potential role of A. baumannii-derived lipopolysaccharides (LPS) as signaling molecules that affect adipocyte functionality. We tested the effect of increasing concentrations of A. baumannii-derived LPS (10, 100, or 1000 ng/mL) on the 3T3-L1 adipocyte cell line. Exposure to LPS was found to increase the expression of several adipokines (e.g., MIP-2, MCP-1, TNF-α, IL-6, lipocalin-2, and FABP4) in 3T3-L1 adipocytes and significantly reduced the expression of leptin and adiponectin. The effects of A. baumannii-derived LPS on MIP-2 expression were similar in comparison with that of LPS prepared from Pseudomonas aeruginosa and Escherichia coli in our cell culture-based system. This study suggests that A. baumannii-derived LPS functions as a signaling molecule that impacts the inflammatory function of white adipose tissue on the level of gene expression.
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10.1155/2017/9039302
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pubmed_573_18595
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The authors present the case of a 37-year-old man who developed a psychotic manic episode and was found to have bilateral basal ganglia calcification (BGC). The authors present this case report along with a discussion of the literature on the neuropsychiatry of BGC.
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10.1176/appi.neuropsych.12090222
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pubmed_667_12180
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The benefit/risk ratio of administering heparin during spinal anaesthesia in patients undergoing total hip replacement (THR) has not been studied widely. We conducted a prospective, randomized, double-blind study to compare low molecular weight heparin (LMWH) for 10 days and placebo in patients undergoing THR performed under spinal anaesthesia associated with gradual compression stockings. Efficacy was assessed by systematic bilateral ascending venography on day 10 +/- 2 in a sequential analysis. Among the 170 patients enrolled, data were available in 153 patients. In the LMWH group (n = 78) the total incidence of deep vein thrombosis (DVT) was 14.1% compared with 37.3% in the placebo group (n = 75) (P = 0.0016). No gross neurological sequelae were observed during the study. This study showed that the addition of LMWH in patients undergoing THR under spinal anaesthesia and wearing gradual compression stockings significantly decreased the incidence of venogram-proved DVT.
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10.1093/bja/78.6.660
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pubmed_368_24368
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Coumarin derivates are oral anticoagulants commonly prescribed for treatment and prevention of thromboembolism. Due to a small therapeutic index and large inter- and intrapatient differences in dose requirements, treatment with coumarins is challenging, particularly in its starting phase. Extensive evidence suggests that common genetic variants in CYP2C9 and VKORC1 genes together with a number of clinical factors are important determinants of the coumarin dose variability. Pharmacogenetic algorithms comprising both genetic and non-genetic factors were developed to improve the safety of coumarin therapy initiation. Recently, three randomized controlled trials (the COAG and the EU-PACT trials) on pharmacogenetic dosing of warfarin, acenocoumarol and phenprocoumon were published. In these trials different coumarin dosing strategies were compared to investigate whether or not pharmacogenetic testing could be beneficial for coumarin management. The purpose of this review was to present and discuss the design and results of these studies within the context of previously published randomized controlled trials and to address the issues surrounding the incorporation of coumarin pharmacogenetic testing into clinical practice.
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10.2174/1566524014666140811114906
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pubmed_1036_5466
|
Defects in insulin signalling and glucose metabolism are associated with the development of diabetes. Insulin signalling is initiated by the binding of insulin to its receptor and triggering cascades of events including activation of PI3kinase/Akt signalling pathway. Calreticulin (CRT) is a calcium binding chaperone molecule located in the endoplasmic reticulum. Targeted deletion of CRT in mice is embryonic lethal as a result of developmental and metabolic abnormalities. Rescued CRT null mice develop severe hypoglycemia the reason for which is not known. In addition, ventricular cardiomyocytes isolated from CRT null (crt-/-) mice have increased glycogen deposits. Therefore, the aim of this study was to investigate the changes in the glucose uptake and insulin signalling pathway (mainly PI3 kinase/Akt) in the absence of CRT. Here we show a significant increase in the glucose uptake by the crt-/- cells. This increase was accompanied by a significant increase in both insulin receptor beta expression, Insulin receptor substrate-1 phosphorylation, GLUT-1 expression and in insulin stimulated Akt phosphorylation and kinase activity in the crt-/- cells. Intriguingly, the increased expression of insulin receptor beta in the crt-/- was due to decreased levels of p53 protein. The current study is the first evidence for the up-regulation of insulin receptor density and activity in the absence of CRT function.
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10.1016/j.bbamcr.2008.08.014
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pubmed_635_1770
|
The small-range millipedes Tasmaniosomaanubis sp. n., Tasmaniosomainterfluminum sp. n. and Tasmaniosomanicolaus sp. n. are described, and the colour of live Tasmaniosomabarbatulum Mesibov, 2010 is documented.
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10.3897/zookeys.488.9460
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pubmed_764_11900
|
We report the performance of a prosopagnosic patient on face learning tasks under different encoding instructions (i.e., levels of processing manipulations). R.J. performs at chance when given no encoding instructions or when given "shallow" encoding instruction to focus on facial features. By contrast, he performs relatively well with "deep" encoding instructions to rate faces in terms of personality traits or when provided with semantic and name information during the study phase. We propose that the improvement associated with deep encoding instructions may be related to the establishment of distinct visually derived and identity-specific semantic codes. The benefit associated with deep encoding in R.J., however, was found to be restricted to the specific view of the face presented at study and did not generalize to other views of the same face. These observations suggest that deep encoding instructions may enhance memory for concrete or pictorial representations of faces in patients with prosopagnosia, but that these patients cannot compensate for the inability to construct abstract structural codes that normally allow faces to be recognized from different orientations. We postulate further that R.J.'s poor performance on face learning tasks may be attributable to excessive reliance on a feature-based left hemisphere face processing system that operates primarily on view-specific representations.
|
10.1017/s1355617700001181
|
pubmed_923_8030
|
The transcriptional enhancer of a chicken U1 small nuclear RNA (snRNA) gene contains a GC-box, an octamer motif, and an SPH motif that are recognized by the transcription factors Sp1, Oct-1, and SBF respectively. Previous work indicated that the octamer and the SPH motifs were both required for U1 gene enhancer activity in frog oocytes when the U1 gene was coinjected with a competing snRNA gene template. Here we show that neither two copies of the octamer motif, nor two copies of the SPH motif, can effectively substitute for the natural combination of octamer and SPH. Furthermore, neither the octamer nor the SPH motif (in the absence of the other) functioned efficiently in combination with a GC-box. Alteration of the spacing between the octamer and SPH motifs also reduced U1 template activity. Several potential cis-acting elements other than the SPH motif, with one possible exception among those tested, were unable to cooperate with the octamer motif to effectively enhance U1 gene expression. These results indicate that rather stringent structural requirements exist with respect to the essential cis-acting motifs present in the U1 enhancer, possibly reflecting the unique properties of the transcription complexes assembled on snRNA gene promoters.
|
10.1093/nar/21.2.281
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pubmed_740_14611
|
INTRODUCTION In New Zealand, extended medicines management roles proposed for pharmacists include the optimisation and monitoring of medicines in patients with long-term conditions through greater collaboration with general practitioners (GPs). Although some collaborative roles have been successfully implemented in hospitals, barriers for both pharmacists and GPs hinder interprofessional working relationships in the community. AIM To compare data from a 2012 study with two previous studies (1998, 2002) examining perceptions of community pharmacists and GPs of the expanding medicines management roles of community pharmacists. METHODS In 2012, a survey, modelled on the 1998 and 2002 studies, was sent to 600 community pharmacists and 600 GPs. Analyses considered the five-point Likert scale to be a continuous variable. A change of ≥ 10% between any two surveys indicated a relevant change for comparison. RESULTS Increasing agreement, which differed considerably between professions, was apparent for most expanding medicine management roles over the 14 study years. In all three studies, pharmacists were open to expanding their roles to include monitoring, screening, advisory and prescribing roles. GPs were most accepting of the traditional dispensing role with a positive shift towards pharmacists' involvement in medicines management over time. DISCUSSION Over 14 years, GPs became more accepting of community pharmacists' involvement in extended medicines management roles, although still had low acceptance of the more clinical roles. Pharmacists considered increased involvement in medicines management as their role, but appeared to lack confidence in their ability to do this role.
|
10.1071/HC16032
|
pubmed_675_8557
|
BACKGROUND
FGFR1 amplification, but not overexpression, has been related to adverse prognosis in hormone-positive breast cancer (HRPBC). Whether FGFR1 overexpression and amplification are correlated, what is their distribution among luminal A or B HRPBC, and if there is a potential different prognostic role for amplification and overexpression are currently unknown features. The role of FGFR1 inhibitors in HRPBC is also unclear.
METHODS
FGFR1 amplification (FISH) and overexpression (RNAscope) were investigated in a N = 251 HRPBC patients cohort and the METABRIC cohort; effects on survival and FISH-RNAscope concordance were determined. We generated hormonal deprivation resistant (LTED-R) and FGFR1-overexpressing cell line variants of the ER+ MCF7 and T47-D and the ER+, FGFR1-amplified HCC1428 cell lines. The role of ER, CDK4/6, and/or FGFR1 blockade alone or in combinations in Rb phosphorylation, cell cycle, and survival were studied.
RESULTS
FGFR1 overexpression and amplification was non-concordant in > 20% of the patients, but both were associated to a similar relapse risk (~ 2.5-fold; P < 0.05). FGFR1 amplification or overexpression occurred regardless of the luminal subtype, but the incidence was higher in luminal B (16.3%) than A (6.6%) tumors; P < 0.05. The Kappa index for overexpression and amplification was 0.69 (P < 0.001). Twenty-four per cent of the patients showed either amplification and/or overexpression of FGFR1, what was associated to a hazard ratio for relapse of 2.6 (95% CI 1.44-4.62, P < 0.001). In vitro, hormonal deprivation led to FGFR1 overexpression. Primary FGFR1 amplification, engineered mRNA overexpression, or LTED-R-acquired FGFR1 overexpression led to resistance against hormonotherapy alone or in combination with the CDK4/6 inhibitor palbociclib. Blocking FGFR1 with the kinase-inhibitor rogaratinib led to suppression of Rb phosphorylation, abrogation of the cell cycle, and resistance-reversion in all FGFR1 models.
CONCLUSIONS
FGFR1 amplification and overexpression are associated to similar adverse prognosis in hormone-positive breast cancer. Capturing all the patients with adverse prognosis-linked FGFR1 aberrations requires assessing both features. Hormonal deprivation leads to FGFR1 overexpression, and FGFR1 overexpression and/or amplification are associated with resistance to hormonal monotherapy or in combination with palbociclib. Both resistances are reverted with triple ER, CDK4/6, and FGFR1 blockade.
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10.1186/s13058-021-01398-8
|
pubmed_633_92
|
The title compound, dipotassium tri-mu-arsenato-scandium(III)tin(IV), is the first arsenate-containing langbeinite to be characterized by single-crystal methods and crystallizes in the aristotype P2(1)3 cubic symmetry for this structure type in which the K(+) ions and the octahedral scandium and tin cations lie on crystallographic threefold axes. The Sc(III) and Sn(IV) ions show a slight segregation over the two octahedral sites, with Sc/Sn populations of 0.582 (5):0.418 (5) on one site and 0.418 (5):0.582 (5) on the other. Bond-valence-sum calculations indicate that the K(+) ions are significantly underbonded in this structure and the O atoms show large anisotropic displacement parameters, as also seen in other langbeinites. The crystal studied was found to be a merohedral twin with a 0.690 (16):0.310 (16) domain ratio.
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10.1107/S0108270110021670
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pubmed_38_12055
|
Lidocaine is commonly used for regional anesthesia and nerve blocks. However, recent clinical studies demonstrated that intravenous perioperative administration of lidocaine can lead to better postoperative analgesia, reduced opioid consumption and improved intestinal motility. It can therefore be used as an alternative when epidural analgesia is contraindicated, not possible or not feasible. Apart from the sodium channel blocking effects relevant for regional anesthesia, lidocaine also has anti-inflammatory properties. Lidocaine can obviously inhibit the priming of resting neutrophilic granulocytes, which, simplified, may reduce the liberation of superoxide anions, a common pathway of inflammation after multiple forms of tissue trauma. At the authors' institutions intravenous lidocaine is primarily used for postoperative pain relief following abdominal surgery and is given as a bolus dose of 1.5-2.0 mg/kg body weight (BW) injected over 5 min followed by an infusion of 1.5 mg/kg BW/h intraoperatively and 1.33 mg/kg BW/h postoperatively in the recovery room or in the intensive care unit (ICU). The lidocaine infusion is stopped in the recovery room 30 min before discharge or in the ICU at the latest after 24 h. Lidocaine is not used on normal wards. This overview summarizes the current evidence for the intravenous administration of lidocaine for patients undergoing different types of surgery and gives practical advice for its use.
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10.1007/s00101-010-1829-0
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pubmed_387_404
|
Between 1978 and 1986, internal iliac artery ligation was performed on eight patients undergoing treatment for severe post-partum hemorrhage, and disseminated intra-vascular coagulation (DIVC) combined with causal pathology was detected in five patients. This procedure was effective in controlling bleeding in eight patients and no hysterectomy was necessary. Post-operative follow-up was uncomplicated in six patients. One patient suffered from post-operative occlusion. Another patient suffered from renal failure, due to secondary cortical renal necrosis. Surgery is usually simple and does not pose any technical problems. This technique allows for the conservation of the reproductive functions, and two of the women became pregnant at a later stage. Obstetric hysterectomy can be avoided by using this technique. It is recommended in cases where DIVC does not respond to medical treatment and can furthermore be used by all surgeons.
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10.1016/0028-2243(88)90031-7
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pubmed_286_13924
|
BACKGROUND
Bone represents one of the most common sites to which breast cancer cells metastasize. Patients experience skeletal related adverse events (pathological fractures, spinal cord compressions, and irradiation for deteriorated pain on bone) even during treatment with zoledronic acid (ZA). Therefore, we conducted a retrospective cohort study to investigate the predictive factors for symptomatic skeletal events (SSEs) in bone-metastasized breast cancer (b-MBC) patients.
METHODS
We retrospectively collected data on b-MBC patients treated with ZA. Patient characteristics, including age, subtype, the presence of non-bone lesions, the presence of multiple bone metastases at the commencement of ZA therapy, duration of ZA therapy, the time interval between breast cancer diagnosis and the initiation of ZA therapy, and type of systemic therapy, presence of previous SSE were analyzed using multivariable logistic regression analysis.
RESULTS
The medical records of 183 patients were reviewed and 176 eligible patients were analyzed. The median age was 59 (range, 30-87) years. Eighty-seven patients were aged ≥60 years and 89 patients were aged < 60 years. The proportions of patients with estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2-positive disease were 81.8%, 63.1%, and 17.6%, respectively. Fifty-three patients had bone-only MBC at the commencement of ZA therapy. SSEs were observed in 42 patients. In the multivariable logistic regression analysis, bone-only MBC but not a breast cancer subtype was an independent risk factor for an SSE during ZA therapy (odds ratio: 3.878, 95% confidence interval: 1.647-9.481; p = 0.002).
CONCLUSIONS
Bone-only MBC patients are more likely to experience an SSE even after treatment with ZA.
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10.1016/j.jbo.2017.08.004
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pubmed_720_19764
|
BACKGROUND
Urinary incontinence (UI) is known to be more prevalent among women and is associated with decline in quality of life. The aim of our study was to investigate the prevalence, risk factors of urinary incontinence and its impact on quality of life among community dwelling older women living in urban and rural populations.
METHODS
This study was conducted based on secondary data analysed from the third phase of the longitudinal study "Neuroprotective Model for Health Longevity among Malaysian Elderly" (LRGS TUA). Stratification of urban and rural study areas were in accordance to that determined by the Department of Statistics. A total of 814 community dwelling older women (53% urban, 47% rural), aged 60 years and above, across four states within Peninsular Malaysia were included in this analysis. Interview-based questionnaires were used to obtain respondents' sociodemographic details and clinical characteristics. The Timed Up and Go test and Handgrip Strength tests were used to assess physical function. Urinary incontinence was self-reported, and quality of life of those with incontinence was assessed using the King's Health Questionnaire (KHQ).
RESULTS
Prevalence of urinary incontinence was 16% and 23% among older women living in urban and rural areas, respectively. Ethnicity was significantly associated with incontinence among older women in both urban and rural population (p < 0.05). Chronic constipation, functional mobility and muscle strength were associated with UI in participants from rural setting (p < 0.05). Binary logistic regression analysis showed that risk of incontinence is lower among Chinese [OR 0.430, 95% C.I: 0.224-0.825, p = 0.011] compared to Malay older women living in urban population. Within the rural population, respondents with chronic constipation [OR: 3.384, 95% C.I: 1.556-7.360, p = 0.002] were found to be at a higher risk of UI. In terms of quality of life, respondents in rural areas experienced more role, physical, social, emotional limitations and sleep disturbance as compared to their urban counterparts (p < 0.05).
CONCLUSION
UI is more prevalent and had a more profound impact on quality of health among older women in the rural setting. The risk factors of UI were ethnicity and chronic constipation among urban and rural older women respectively. It is important to provide holistic strategies in the prevention and management of UI among older women especially within the rural population.
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10.1186/s12889-019-6870-6
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pubmed_972_8793
|
We consider weighted logrank tests for interval censored data when assessment times may depend on treatment, and for each individual, we only use the two assessment times that bracket the event of interest. It is known that treating finite right endpoints as observed events can substantially inflate the type I error rate under assessment-treatment dependence (ATD), but the validity of several other implementations of weighted logrank tests (score tests, permutation tests, multiple imputation tests) has not been studied in this situation. With a bounded number of unique assessment times, the score test under the grouped continuous model retains the type I error rate asymptotically under ATD; however, although the approximate permutation test based on the permutation central limit theorem is not asymptotically valid under every ATD scenario, we show through simulation that in many ATD scenarios, it retains the type I error rate better than the score test. We show a case where the approximate permutation test retains the type I error rate when the exact permutation test does not. We study and modify the multiple imputation logrank tests of Huang, Lee, and Yu (2008, Statistics in Medicine, 27: 3217-3226), showing that the distribution of the rank-like scores asymptotically does not depend on the assessment times. We show through simulations that our modifications of the multiple imputation logrank tests retain the type I error rate in all cases studied, even with ATD and a small number of individuals in each treatment group. Simulations were performed using the interval R package.
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10.1002/sim.5447
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pubmed_819_4256
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The effects of caffeine on rate-force relation and their Ca++ dependence were studied in canine cardiac Purkinje fibers. At constant rate, caffeine increased and then decreased force. During drives at different rates (15, 60 and 120/min), 1 mM caffeine caused the largest positive inotropic effect at the slowest rate, but in 8.1 mM [Ca++]o caffeine no longer increased force even at 15/min. Interruptions of drive were followed by a positive and then a negative staircase: caffeine (1-4 mM) blunted these effects. A sudden decrease in rate caused a positive staircase: caffeine decreased and caffeine plus 8.1 mM [Ca++]o abolished it. A sudden increase in rate caused a negative staircase and on recovery a positive staircase: caffeine reduced and caffeine plus 8.1 mM [Ca++]o could reverse them. In low [Ca++]o (0.54 mM), caffeine caused only a positive inotropic effect and did not modify the rate-force relation patterns. High [Ca++]o ( > 8.1 mM) reversed the staircase patterns induced by a rate increase; adding caffeine shifted the reversal to lower [Ca++]o. Low [Na]o altered the rate-force relation similarly to high [Ca++]o, and caffeine exaggerated its effects. Decreasing [Ca++]i by means of tetrodotoxin or high [K+]o antagonized the caffeine effects on the rate-force relation. We conclude that caffeine markedly modulates the rate-force relation through a Ca(++)-dependent mechanism. This mechanism appears to involve a supraoptimal increase in [Ca++]i rather than a decrease in Ca++ released during the action potential.
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pubmed_819_4256
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pubmed_732_20609
|
The GC-rich bacterial species, Aeromonas salmonicida, is parasitised by both GC-rich phages (Aeromonas phages - phiAS7 and vB_AsaM-56) and GC-poor phages (Aeromonas phages - 25, 31, 44RR2.8t, 65, Aes508, phiAS4 and phiAS5). Both the GC-rich Aeromonas phage phiAS7 and Aeromonas phage vB_AsaM-56 have nearly identical codon usage bias as their host. While all the remaining seven GC-poor Aeromonas phages differ dramatically in codon usage from their GC-rich host. Here, we investigated whether tRNA encoded in the genome of Aeromonas phages facilitate the translation of phage proteins. We found that tRNAs encoded in the phage genome correspond to synonymous codons overused in the phage genes but not in the host genes.
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pubmed_732_20609
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pubmed_407_21236
|
Encephalitis has been described as a rare complication of pandemic 2009 (H1N1) influenza A infection in children and adolescents. This report is on two adult patients who presented with encephalitis in relation to acute H1N1 influenza. Encephalitis is therefore also a potential complication of pandemic 2009 (H1N1) influenza infection in adults.
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pubmed_407_21236
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pubmed_468_14957
|
Soft tissue sarcomas are a heterogeneous group of malignant mesenchymal tumors, and novel tumors biomarkers and therapeutic targets are required to achieve early diagnosis and optimize therapy for individual patients. Global protein expression studies, an approach known as "proteomics", can offer important clues for understanding tumor biology that cannot be obtained by other approaches. Proteomic studies, such as two-dimensional difference gel electrophoresis (2D-DIGE) and mass spectrometry, have provided protein expression profiles of soft tissue tumors that can be used to develop novel diagnostic and therapeutic biomarkers and allow molecular classification of tumors. In this article, a brief description of the methodology will be provided, followed by a few examples of the recent proteomic studies that have generated new information for the diagnosis, classification and treatment of soft tissue tumors.
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10.1007/s10147-011-0203-9
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pubmed_982_22080
|
Pediatric wards in South Africa are largely occupied by children with AIDS-related illnesses. This study uses qualitative inquiry involving focus groups with nurses into the needs of children, caregivers, and healthcare providers. The findings indicate changes to the nature of nursing practice, knowledge of nursing, and ethics of nursing care.
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10.1097/00004650-200609000-00008
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pubmed_698_15610
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Many studies that aim to characterize the proteome require the production of pure protein in a high-throughput format. We have developed a system for high-throughput subcloning, protein expression and purification that is simple, fast, and inexpensive. We utilized ligation-independent cloning with a custom-designed vector and developed an expression screen to test multiple parameters for optimal protein production in E. coli. A 96-well format purification protocol that produced microgram quantities of pure protein was also developed.
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10.1021/pr025554a
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pubmed_578_5854
|
Memory formation requires changes in gene expression, which are regulated by the activation of transcription factors and by changes in epigenetic factors. Poly[ADP]-ribosylation of nuclear proteins has been postulated as a chromatin modification involved in memory consolidation, although the mechanisms involved are not well characterized. Here we demonstrate that poly[ADP]-ribose polymerase 1 (PARP-1) activity and the poly[ADP]-ribosylation of proteins over a specific time course is required for the changes in synaptic plasticity related to memory stabilization in mice. At the molecular level, histone H1 poly[ADP]-ribosylation was evident in the hippocampus after the acquisition period, and it was selectively released in a PARP-1-dependent manner at the promoters of cAMP response element-binding protein and nuclear factor-κB dependent genes associated with learning and memory. These findings suggest that histone H1 poly[ADP]-ribosylation, and its loss at specific loci, is an epigenetic mechanism involved in the reprogramming of neuronal gene expression required for memory consolidation.
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10.1523/JNEUROSCI.3010-10.2010
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pubmed_484_4141
|
STATEMENT OF PURPOSE
Indirect markers are consistent with greater oxidative stress in autism. They include greater free-radical production, impaired energetics and cholinergics, and higher excitotoxic markers. Brain and gut, both abnormal in autism, are particularly sensitive to oxidative injury. Higher red-cell lipid peroxides and urinary isoprostanes in autism signify greater oxidative damage to biomolecules. A preliminary study found accelerated lipofuscin deposition--consistent with oxidative injury to autistic brain in cortical areas serving language and communication. Double-blind, placebo-controlled trials of potent antioxidants--vitamin C or carnosine--significantly improved autistic behavior. Benefits from these and other nutritional interventions may be due to reduction of oxidative stress. Understanding the role of oxidative stress may help illuminate the pathophysiology of autism, its environmental and genetic influences, new treatments, and prevention.
OBJECTIVES
Upon completion of this article, participants should be able to: 1. Be aware of laboratory and clinical evidence of greater oxidative stress in autism. 2. Understand how gut, brain, nutritional, and toxic status in autism are consistent with greater oxidative stress. 3. Describe how anti-oxidant nutrients are used in the contemporary treatment of autism.
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pubmed_484_4141
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pubmed_866_1366
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Recently, lanthanide-doped luminescent materials have been widely studied and most investigations have been limited to rare-earth-containing fluorides formed with lighter alkali metals (Li, Na and K). Hence, it is important to understand the luminescence properties of cesium rare-earth fluorides. Herein, a novel type of multi-functional luminescent material, hexagonal β-CsRe2F7 (Re = La-Lu, Y, Sc) nanocrystals, is successfully prepared via in situ crystallization inside glass. Specifically, Yb/Er:β-CsLu2F7@glass exhibits a much higher upconversion quantum yield than Yb/Er:β-NaYF4@glass (about 6 times), which is believed to be one of the most efficient upconversion materials so far. Impressively, Er:CsYb2F7@glass shows a significant photothermal effect, which can produce variable upconversion emission colors induced by an incident 980 nm laser diode, enabling it to find practical application in novel/high-precision anti-counterfeiting. In addition, Ce:CsLu2F7@glass with a maximal photoluminescence quantum yield reaching 67% can yield intense X-ray excitable radioluminescence, which is even higher than that of a commercial Bi4Ge3O12 scintillator. Benefitting from the effective protection of robust oxide glass, lanthanide-doped CsRe2F7 nanocrystals show long-term stability in harsh environments, retaining near 100% luminescence after directly immersing them in water/oil for 30 days. It is expected that the present nanocomposites have potential applications in the fields of high-end upconversion anti-counterfeiting and high-energy radiation detection.
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10.1039/c9nr08656k
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pubmed_149_19279
|
BACKGROUND
Cystic pulmonary fibrosis (CF) affects mostly the lung of the newborns. Chronic infection and inflammation become the major causes of morbidity and mortality in CF. However, the underlying molecular mechanisms causing CF still remain unclear.
METHODS
ELISA assay was used to examine the expression of HE4 and pro-inflammatory cytokines in W126VA4 cells supernatant fluid. qRT-PCR was applicable to determine the mRNA level of HE4, α-SMA, collagen 1, MMP2, MMP9 and various interleukins. Immunofluorescent assay was used to test the expression of HE4 in WI-26 VA4 cells. Major elements of MAPK and NF-κB signals pathways were examined by western blot.
RESULTS
We found higher expression of HE4 in CF patients serum and lung biopsy. Interestingly, HE4 expression was positively correlated with fibrosis markers expression. In addition,HE4 overexpression increased inflammatory cytokines secretion and fibrosis markers expression in WI-26 VA4 cells. And NF-κB pathways were responsible for elevated inflammation. In addition, HE4/MAPK/MMPs signaling cascades destroyed the normal extracellular matrix (ECM) and promoted fibrosis.
CONCLUSIONS
Overall, we first identified that HE4 promoted CF-associated inflammation. Additionally, NF-κB and MAPK signalings were further validated to be responsible for CF-associated inflammation and ECM destruction. Characterization of lumacaftor/ivacaftor in CF-associated inflammation may provide a novel insight into clinical CF treatment.
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10.1007/s13258-019-00836-4
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pubmed_211_14348
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The topoisomerase I inhibitor GL147211C [7-[(4-methylpiperazino)methyl]-10,11-(ethylenedioxy)-(20S)-campto thecin trifluoroacetate], a camptothecin analogue, has significant activity in tumor cell cytotoxicity assays in vitro and antitumor activity in both animal tumor models and human patients. Its toxicity is significant, however, effectively limiting the amount of drug that can be administered and its clinical utility. To determine whether the therapeutic index of GL147211C could be improved, the drug was encapsulated in long-circulating, pegylated (STEALTH) liposomes (SPI-355). The pharmacokinetics and antitumor activity of SPI-355 were compared to those of nonliposomal GL147211C. The plasma pharmacokinetics of SPI-355 in rats were typical of those of other pegylated liposomal formulations, with significantly increased blood circulation time; the dose-corrected area under the curve and Cmax of SPI-355 (10 mg/kg) were 1250- and 35-fold higher, respectively, than those of nonliposomal GL14711C (8.72 mg/kg). The comparative antitumor activity of SPI-355 and nonliposomal GL1472211C was evaluated in nude mice implanted with HT29 colon carcinoma xenografts. SPI-355 was 20-fold more effective than GL147211C in inhibiting tumor growth (1 mg/kg SPI-355 and 20 mg/kg GL147211C) and produced durable complete remissions of tumors at well-tolerated dose levels that were >5-fold lower than the maximally tolerated dose of GL147211C, which induced no durable complete responses. Signs of toxicity were similar between the two drugs, but liposome encapsulation increased the toxicity of drug approximately 4-fold, with increased weight loss and several deaths with SPI-355 (5 mg/kg SPI-355 versus 20 mg/kg GL147211C). Despite the increased toxicity seen with SPI-355, the therapeutic index of the liposomal formulation was increased approximately 5-fold over that of nonliposomal GL147211C, suggesting that such a pegylated liposomal formulation could demonstrate increased therapeutic index in human patients.
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pubmed_211_14348
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pubmed_954_22262
|
The anticoagulant serpin, protein Z-dependent protease inhibitor (ZPI), circulates in blood as a tight complex with its cofactor, protein Z (PZ), enabling it to function as a rapid inhibitor of membrane-associated factor Xa. Here, we show that N,N'-dimethyl-N-(acetyl)-N'-(7-nitrobenz-3-oxa-1,3-diazol-4-yl)ethylenediamine (NBD)-fluorophore-labeled K239C ZPI is a sensitive, moderately perturbing reporter of the ZPI-PZ interaction and utilize the labeled ZPI to characterize in-depth the thermodynamics and kinetics of wild-type and variant ZPI-PZ interactions. NBD-labeled K239C ZPI bound PZ with ∼3 nM KD and ∼400% fluorescence enhancement at physiologic pH and ionic strength. The NBD-ZPI-PZ interaction was markedly sensitive to ionic strength and pH but minimally affected by temperature, consistent with the importance of charged interactions. NBD-ZPI-PZ affinity was reduced ∼5-fold by physiologic calcium levels to resemble NBD-ZPI affinity for γ-carboxyglutamic acid/EGF1-domainless PZ. Competitive binding studies with ZPI variants revealed that in addition to previously identified Asp-293 and Tyr-240 hot spot residues, Met-71, Asp-74, and Asp-238 made significant contributions to PZ binding, whereas Lys-239 antagonized binding. Rapid kinetic studies indicated a multistep binding mechanism with diffusion-limited association and slow complex dissociation. ZPI complexation with factor Xa or cleavage decreased ZPI-PZ affinity 2-7-fold by increasing the rate of PZ dissociation. A catalytic role for PZ was supported by the correlation between a decreased rate of PZ dissociation from the K239A ZPI-PZ complex and an impaired ability of PZ to catalyze the K239A ZPI-factor Xa reaction. Together, these results reveal the energetic basis of the ZPI-PZ interaction and suggest an important role for ZPI Lys-239 in PZ catalytic action.
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10.1074/jbc.M114.633479
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pubmed_680_12263
|
We found that in regenerative erythropoiesis, the erythroid progenitor landscape is reshaped, and a previously undescribed progenitor population with colony-forming unit-erythroid (CFU-E) activity (stress CFU-E [sCFU-E]) is expanded markedly to restore the erythron. sCFU-E cells are targets of erythropoietin (Epo), and sCFU-E expansion requires signaling from the Epo receptor (EpoR) cytoplasmic tyrosines. Molecularly, Epo promotes sCFU-E expansion via JAK2- and STAT5-dependent expression of IRS2, thus engaging the progrowth signaling from the IGF1 receptor (IGF1R). Inhibition of IGF1R and IRS2 signaling impairs sCFU-E cell growth, whereas exogenous IRS2 expression rescues cell growth in sCFU-E expressing truncated EpoR-lacking cytoplasmic tyrosines. This sCFU-E pathway is the major pathway involved in erythrocytosis driven by the oncogenic JAK2 mutant JAK2(V617F) in myeloproliferative neoplasm. Inability to expand sCFU-E cells by truncated EpoR protects against JAK2(V617F)-driven erythrocytosis. In samples from patients with myeloproliferative neoplasm, the number of sCFU-E-like cells increases, and inhibition of IGR1R and IRS2 signaling blocks Epo-hypersensitive erythroid cell colony formation. In summary, we identified a new stress-specific erythroid progenitor cell population that links regenerative erythropoiesis to pathogenic erythrocytosis.
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10.1182/blood.2022016741
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pubmed_118_25156
|
OBJECTIVE:
To evaluate in vivo changes in the color of esthetic elastomeric ligatures from different manufacturers.
METHODS:
Four widely used commercial brands of elastomeric ligatures were selected and used in 20 adult patients in a split-mouth design. The ligatures were evaluated by orthodontists and patients in a double-blind manner on the day the ligatures were placed (T0) and 30 days after intraoral exposure (T1) by means of a system of staining scores. Groups were compared by Friedman test with p < 0.05.
RESULTS:
Orthodontists and patients reported similar staining scores (p > 0.05). Results showed that all brands underwent significant staining when exposed to the intraoral environment. Modular-crystal MorelliTM (Sorocaba, SP, Brazil) showed the highest degree of staining with the median reaching the maximum value (3); while the other brands (3M UnitekTM, American OrthodonticsTM and GAC DentsplyTM) showed the median equal to 1 (p < 0.001). A large individual variability in the degree of staining was also found for all brands.
CONCLUSIONS:
All four brands of esthetic ligatures showed significant staining, which appeared to be more pronounced for the MorelliTM brand. Changes in color of the elastomeric ligatures were perceived similarly by patients and orthodontists. The industry needs to improve the color stability of esthetic ligatures.
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10.1590/2177-6709.21.5.053-057.oar
|
pubmed_1048_14512
|
The present experiment was designed to assess the effects of seed soaking with 24-epibrassinolide (EBR) on the physiology of Brassica juncea L. seedlings grown under imidacloprid (IMI) toxicity. Application of EBR increased the length of seedlings, dry weight, and pigment contents, polyphenols, total phenols, and organic acids under IMI toxicity. The expression of genes coding key enzymes of pigment, phenols, polyphenols, and organic acid biosynthetic pathways was also studied including CHLASE (chlorophyllase), PSY (phytoene synthase), CHS (chalcone synthase) and PAL (phenylalanine ammonialyase), CS (citrate synthase), SUCLG1 (succinyl Co-A ligase,), SDH (succinate dehydrogenase), FH (fumarate hydratase), MS (malate synthase). Multiple linear regression (MLR) analysis revealed that IMI application regressed negatively on seedling length, dry weight and total chlorophyll content. However, EBR seed treatment regressed positively on all the parameters studied. Moreover, interaction between IMI and EBR showed positive regression for growth parameters, content of pigments, total polyphenol, total phenol and malate, and expression of PSY and PAL. Negative interactions were noticed for the contents of fumarate, succinate and citrate, and expression of CHS and all genes studied related to organic acid metabolism. In conclusion, EBR enhanced the growth and contents of all studied metabolites by regulating the gene expression of B. juncea seedlings under IMI stress.
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10.3389/fpls.2016.01569
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pubmed_675_16486
|
AIMS
The NHS Long Term Plan has a prevention focus and ambition to support patients to self-manage disease through improving health behaviours. An essential requirement of self-management is behaviour change, but many practitioners have not been trained in skills to support behaviour change. 'Healthy Conversation Skills' (HCS) training was developed at the University of Southampton for this purpose. This article reports on a pilot study that aimed to assess the feasibility of primary care practitioners adopting HCS in their routine practice. It describes their experiences and level of competence post-training.
METHODS
Health Education England (Wessex) commissioned HCS training for 18 primary care practitioners. Fifteen of these practitioners were subsequently observed in their consultations at one or two time points; face-to-face semi-structured, reflective feedback interviews were conducted immediately following the observations. Practitioners' HCS competence was assessed from the observations and interviews using a previously developed and published coding rubric. The interview data were analysed thematically to understand practitioners' experiences of using the new skills.
RESULTS
Practitioners demonstrated competence in embedding the skills into their routine practice following HCS training. They reflected on how patients liked being asked questions, the usefulness of setting SMARTER (Specific, Measured, Action-oriented, Realistic, Timed, Evaluated and Reviewed) goals and the power of listening. They could also identify facilitators of skill use and ways to overcome challenges such as patients with competing priorities and organisational constraints. They found the skills valuable as a way of empowering patients to make changes to manage their own health.
CONCLUSIONS
HCS are acceptable to primary care practitioners, can be readily adopted into their routine consultations and are a helpful strategy for supporting patients to make changes. HCS training has the potential to be a sustainable, scalable and effective way of contributing to the prevention agenda by supporting disease self-management, and hence of addressing today's epidemic of lifestyle-related conditions.
|
10.1177/1757913920977030
|
pubmed_617_23005
|
BACKGROUND
Biphenotypic acute leukemia (BAL) is a distinct entity that is immunophenotypically defined by the European Group for the Immunological Classification of Leukemia (EGIL) scoring system and accounts for less than 5% of all acute leukemia cases. Since it is a rare and heterogeneous form of acute leukemia with an allegedly poor outcome, there is no consensus on the best treatment approach in these patients. Our objective was to analyze the biological features and outcome of patients diagnosed with BAL in our institution.
PATIENTS AND METHODS
Using the EGIL system, we identified 21 cases (3.9%) of BAL from 535 newly diagnosed acute leukemia patients in an 11-year period.
RESULTS
There were ten cases of myeloid+B-lymphoid leukemia, eight cases of myeloid+T-lymphoid, one case of B+T-lymphoid and two cases of trilineage (myeloid+B+T-lymphoid leukemia). The complete remission (CR) rate with high-dose chemotherapy was 72% and overall survival at 5 years was 21%. Patients that received acute lymphoblastic leukemia-oriented chemotherapy had a higher CR rate compared with those who received acute myeloid leukemia-oriented chemotherapy (100% vs. 60%, P = .007). The white blood cell count at diagnosis was found to have statistically significant impact on survival.
CONCLUSION
Despite the progress in the treatment of acute leukemia, the prognosis of BAL remains poor and treatment protocols devised explicitly for this entity should be investigated in prospective collaborative studies.
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10.1016/s1658-3876(08)50009-4
|
pubmed_373_8955
|
Silane coupling agents containing a fluorocarbon chain were prepared in high yields. It was found that silanes can be useful modifiers of the surfaces of glass, metals, and resin composites for dental use. The silane coupling agent CF3(CF2)9CH2CH2Si(OCH3)3 was the best modifier of these surfaces in terms of water and oil repellency. Colorants and experimental bacterial plaque detached much more easily from, and adhered less well to, surfaces modified with this silane coupling agent compared with unmodified surfaces. The surfaces of four teeth of a denture were modified with this silane coupling agent by spreading the agent on the surfaces with a small brush followed by brief drying with a hair drier. The modified tooth surfaces of the denture, which was worn for four months in a heavy smoker's oral cavity, were more stain-resistant than the unmodified tooth surfaces. It is expected that silane coupling agents containing a fluorocarbon chain will be surface modifiers for enhancement of oral health.
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10.1163/156856297x00218
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pubmed_825_10329
|
Mice were treated with griseofulvin (GF) containing diet or control diet for 12 months. The livers from mice fed griseofulvin showed large tumors that were excised and used for analysis. The infrared spectra from control liver tissue and tumor tissue from GF livers were measured and compared as a function of pressure up to 27 kbar. Many changes in the infrared spectral features of the tumor tissue were observed. Results showed that neoplasm formation involved structural modifications of nucleic acids, lipids, carbohydrates, and proteins in the liver cells, which were detected from the abnormal vibrations of the functional groups in these biomolecules. The amount of glycogen was dramatically decreased in the tumor tissue compared to the control tissue. Important changes in the strength of hydrogen-bondings in the phosphodiester backbone of the nucleic acids and in the C-O groups of tissue proteins and carbohydrates were observed. Stronger interchain interactions and thus close interchain packing among the lipids in the GF liver were evident. These results showed very close similarities with those obtained with other types of tumors such as human colon cancer, suggesting that a common pattern of molecular changes has been identified in neoplastic transformation.
|
10.1016/0014-4800(91)90007-k
|
pubmed_532_8819
|
Arthrobacter sp. CGMCC 3584 are able to produce cAMP from glucose by the purine synthesis pathway via de novo or salvage biosynthesis. In order to gain an improved understanding of its metabolism, (13)C-labeling experiment and gas chromatography-mass spectrometry (GC-MS) analysis were employed to determine the metabolic network structure and estimate the intracellular fluxes. GC-MS analysis helps to reflect the activity of the intracellular pathways and reactions. The metabolic network mainly contains glycolytic and pentose phosphate pathways, the tricarboxylic acid cycle, and the inactive glyoxylate shunt. Hypoxanthine as a precursor of cAMP and sodium fluoride as an inhibitor of glycolysis were found to increase the cAMP production, as well as the flux through the PP pathway. The effects of adding hypoxanthine and sodium fluoride are discussed based on the enzyme assays and metabolic flux analysis. In conclusion, our results provide quantitative insights into how cells manipulate the metabolic network under different culture conditions and this may be of value in metabolic regulation for desirable production.
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pubmed_532_8819
|
pubmed_675_10169
|
The cobas® Liat® Influenza A/B and respiratory syncytial virus assay was tested on nasopharyngeal aspirates. The resolution of invalid samples was performed using a preanalytical step. cobas® Liat® can be used on nasopharyngeal aspirates with a preanalytical processing step, with a slightly diminished performances in detecting respiratory syncytial virus but not for influenza.
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10.1016/j.diagmicrobio.2021.115326
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pubmed_625_3082
|
Rapid and specific detection of single nucleotide polymorphisms (SNPs) related to drug resistance in infectious diseases is crucial for accurate prognostics, therapeutics and disease management at point-of-care. Here, we present a novel amplification method and provide universal guidelines for the detection of SNPs at isothermal conditions. This method, called USS-sbLAMP, consists of SNP-based loop-mediated isothermal amplification (sbLAMP) primers and unmodified self-stabilizing (USS) competitive primers that robustly delay or prevent unspecific amplification. Both sets of primers are incorporated into the same reaction mixture, but always targeting different alleles; one set specific to the wild type allele and the other to the mutant allele. The mechanism of action relies on thermodynamically favored hybridization of totally complementary primers, enabling allele-specific amplification. We successfully validate our method by detecting SNPs, C580Y and Y493H, in the Plasmodium falciparum kelch 13 gene that are responsible for resistance to artemisinin-based combination therapies currently used globally in the treatment of malaria. USS-sbLAMP primers can efficiently discriminate between SNPs with high sensitivity (limit of detection of 5 × 101 copies per reaction), efficiency, specificity and rapidness (<35 min) with the capability of quantitative measurements for point-of-care diagnosis, treatment guidance, and epidemiological reporting of drug-resistance.
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10.1021/acs.analchem.8b02416
|
pubmed_975_13169
|
A valuable approach to investigating a biological process is to study the effect of mutations in the involved genes. By studying a diverse set of such mutations, one can gain important insights into the roles that the given gene product plays in the biological process. Although this approach has long been recognized, the scarcity of mammalian mutations has largely limited such investigations to simple organisms. It has recently been shown that highly efficient mutagenesis of the mouse germline with a random point mutagen can produce mutations that are valuable in several important ways. First, it can produce numerous different types of mutations. Second, it can be used to mutate genes that have yet to be cloned or characterized. Genes that have been marked by mutation can ultimately yield molecular access after mapping to high resolution and cloning from map position. Such new investigative capabilities will ultimately allow one to gain intimate knowledge of the molecular basis of complex biological processes like behavior and development. Third, mutations can be induced that yield animal models of human heritable diseases. Such disease models allow for intensive research into the etiology of the given disease and also permit the facile evaluation of new therapeutic regimens.
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10.3181/00379727-209-43905
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pubmed_410_16479
|
Thoracic blunt trauma is evident in up to one-fifth of all hospital admissions, and is second only to head trauma in motor vehicle crashes. One of the most problematic injury mechanisms associated with blunt thoracic trauma is pulmonary contusion, occurring in up to 75% of blunt thoracic trauma cases. The source and effects of pulmonary contusion caused by blunt lung injury are not well defined, especially within the field of continuum biomechanics. This, paired with unreliable diagnostics for pulmonary contusion, leads to uncertainty in both the clinical entity and mechanics of how to predict the presence of injury. There is a distinct need to combine the clinical aspects with mechanical insights through the identification and mitigation of blunt lung trauma and material testing and modeling. This is achieved through using the mechanical insights of lung tissue behavior in order to better understand the injurious mechanisms and courses of treatment of blunt-caused pulmonary contusion. This paper hopes to act as a step forward in connecting two perspectives of blunt lung injury, the clinical entity, and mechanical testing and modeling, by reviewing the known literature and identifying the unknowns within the two related fields. Through a review of related literature, clinical evidence is correlated to mechanical data to gain a better understanding of what is being missed in identification and response to blunt lung injury as a whole.
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10.1115/1.4054057
|
pubmed_689_16384
|
Plants produce low molecular weight compounds with antimicrobial activity in response to microbial attack termed phytoalexins. The first phytoalexin identified was (+) pisatin from pea, and several fungi are able to detoxify pisatin to a less inhibitory compound, including F. oxysporum f. sp. pisi. This detoxification is catalyzed by demethylation of the compound (termed pisatin demethylase activity, or PDA) by the cytochrome P450, Pda. Here we detail two procedures to assess PDA using radiolabeled [14C]pisatin as a substrate and monitoring activity using a scintillation counter.
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10.1007/978-1-0716-1795-3_15
|
pubmed_163_18020
|
The COVID-19 pandemic caused by SARS-CoV-2 has become a major threat across the globe. Here, we developed machine learning approaches to identify key pathogenic regions in coronavirus genomes. We trained and evaluated 7,562,625 models on 3,665 genomes including SARS-CoV-2, MERS-CoV, SARS-CoV, and other coronaviruses of human and animal origins to return quantitative and biologically interpretable signatures at nucleotide and amino acid resolutions. We identified hotspots across the SARS-CoV-2 genome, including previously unappreciated features in spike, RdRp, and other proteins. Finally, we integrated pathogenicity genomic profiles with B cell and T cell epitope predictions for enrichment of sequence targets to help guide vaccine development. These results provide a systematic map of predicted pathogenicity in SARS-CoV-2 that incorporates sequence, structural, and immunologic features, providing an unbiased collection of genetic elements for functional studies. This metavirome-based framework can also be applied for rapid characterization of new coronavirus strains or emerging pathogenic viruses.
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10.1016/j.patter.2021.100407
|
pubmed_407_867
|
When engaging in joint attention, one person directs another person's attention to an object (Initiating Joint Attention, IJA), and the second person's attention follows (Responding to Joint Attention, RJA). As such, joint attention must occur within the context of a social interaction. This ability is critical to language and social development; yet the neural bases for this pivotal skill remain understudied. This paucity of research is likely due to the challenge in acquiring functional MRI data during a naturalistic, contingent social interaction. To examine the neural bases of both IJA and RJA we implemented a dual-video set-up that allowed for a face-to-face interaction between subject and experimenter via video during fMRI data collection. In each trial, participants either followed the experimenter's gaze to a target (RJA) or cued the experimenter to look at the target (IJA). A control condition, solo attention (SA), was included in which the subject shifted gaze to a target while the experimenter closed her eyes. Block and event-related analyses were conducted and revealed common and distinct regions for IJA and RJA. Distinct regions included the ventromedial prefrontal cortex for RJA and intraparietal sulcus and middle frontal gyrus for IJA (as compared to SA). Conjunction analyses revealed overlap in the dorsal medial prefrontal cortex (dMPFC) and right posterior superior temporal sulcus (pSTS) for IJA and RJA (as compared to SA) for the event analyses. Functional connectivity analyses during a resting baseline suggest joint attention processes recruit distinct but interacting networks, including social-cognitive, voluntary attention orienting, and visual networks. This novel experimental set-up allowed for the identification of the neural bases of joint attention during a real-time interaction and findings suggest that whether one is the initiator or responder, the dMPFC and right pSTS, are selectively recruited during periods of joint attention.
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10.3389/fnhum.2012.00169
|
pubmed_559_9260
|
BACKGROUND
As the major target of Angiotensin II (Ang II) in the vessel wall, vascular smooth muscle cells (VSMCs) are a tentative source to produce C-reactive protein (CRP). However, it is largely unknown if Ang II is capable of inducing CRP production in VSMCs.
METHODS AND RESULTS
Ang II induced a concentration-dependent release of CRP in cultured rat VSMCs as measured by sandwich ELISA. Real-time PCR revealed that Ang II significantly upregulated CRP mRNA level in vitro. Ang II-induced CRP generation in aortic VSMCs was also investigated using double-labeled fluorescent immunohistochemistry and in situ hybridization in subchronic Ang II administration in rats. Losartan but not PD123319 markedly blocked the Ang II-induced CRP production in cultured VSMCs, suggesting that such effect was mediated via Ang II type 1 receptor. Further, Western blotting analysis showed that mitogen-activated protein kinase (MAPK) activation was obligatory in Ang II-induced CRP production, since specific MAPK inhibitor PD098059 almost abolished the action.
CONCLUSIONS
We identified that Ang II is capable of inducing CRP generation in VSMCs, in which Ang II type 1 receptor followed by MAPK signal pathway is involved. It strengthened the role of Ang II-induced CRP production by VSMCs in the inflammatory process in atherosclerosis.
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10.1016/j.atherosclerosis.2006.09.007
|
pubmed_612_25271
|
BACKGROUND
Caesarean delivery is an essential surgical skill within the primary care setting aimed at reducing maternal morbidity and mortality.
OBJECTIVES
To determine the rate and indications for caesarean deliveries with a view to improving on the service delivery in the study area.
METHODS
A retrospective review of all caesarean deliveries over a five-year period, January 1st, 2012 to December 31st, 2016.
RESULTS
A total of 2321 deliveries were recorded during the study duration and 481 of them were through caesarean section (CS) giving a caesarean section rate of 20.4%. The rate was higher in the multigravida 255 (53.1%). The commonest indication for caesarean section was previous caesarean section 131 (27.2%). Emergency caesarean delivery accounted for 278 (57.8%). Only 16 (3.3%) stayed more than five days postoperatively while the rest, 465 (96.7%), stayed less than five days. There was a gradual yearly increase in rate from 12.1% in 2012 to 19.5% in 2016.
CONCLUSION
The rate of CS in this study has shown a gradual yearly increase with emergency CS having a higher percentage. Early diagnosis and referral of high-risk pregnancies from peripheral hospitals could reduce emergency CS among the study population.
|
10.4314/ahs.v21i1.41
|
pubmed_321_14400
|
Wolbachia (Hertig) endosymbionts are extensively studied in a wide range of organisms and are known to be transmitted through the egg cytoplasm to the offsping. Wolbachia may cause several types of reproductive modifications in arthropods. In Trichogramma species, parthenogenesis-inducing Wolbachia bacteria allow females wasps to produce daughters from unfertilized eggs and these bacteria are present in at least 9% of all Trichogramma species. Phylogenetic studies have led to the subdivision of the Wolbachia clade in five supergroups (A, B, C, D and E) and Wolbachia from Trichogramma belong to supergroup B. Here, using the wsp gene, four groups of Wolbachia that infect Trichogramma species were distinguished and the addition of a new group "Ato" was suggested due to the addition of Wolbachia from Trichogramma atopovirilia (Oatman and Platner). Specific primers were designed and tested for the "Ato" group. Seventy-five percent of all evaluated Wolbachia strains from Trichogramma fell within "Sib" group.
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10.1590/1519-6984.166671
|
pubmed_226_21559
|
BACKGROUND
In patients with acute intermittent porphyria (AIP), induction of delta aminolevulinic acid synthase 1 (ALAS1) leads to haem precursor accumulation that may cause recurring acute attacks. In a recent phase III trial, givosiran significantly reduced the attack rate in severe AIP patients. Frequent adverse events were injection-site reaction, fatigue, nausea, chronic kidney disease and increased alanine aminotransferase.
OBJECTIVES
To describe the efficacy and safety of givosiran based on a personalized medical approach.
METHODS
We conducted a retrospective patient file study in 25 severe AIP patients treated with givosiran in France. We collected data on clinical and biochemical efficacy along with reports of adverse events.
RESULTS
Givosiran drastically reduced the attack rate in our cohort, as 96% were attack-free at the time of the study. The sustained efficacy of givosiran in most patients allowed us to personalize dosing frequency. In 42%, givosiran was only given when haem precursor levels were increasing. Our data suggest that givosiran is most effective when given early in the disease course. We confirmed a high prevalence of adverse events. One patient discontinued treatment due to acute pancreatitis. All patients had hyperhomocysteinemia, and all patients with initial homocysteine levels available showed an increase under treatment. In this context, one patient was diagnosed with pulmonary embolism.
CONCLUSION
The sustained effect of givosiran allowed a decrease in dosing frequency without compromising treatment efficacy. The high prevalence of adverse events emphasizes the importance of restricting the treatment to severe AIP and administering the minimum effective dose for each patient.
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10.1016/j.ymgme.2022.01.002
|
pubmed_781_23700
|
Natural compounds with antioxidant activity can be useful for treatment of reactive oxygen species-related diseases, comprising atherosclerosis, inflammatory injury, cardiovascular disease, cancer, diabetes, Alzheimer's disease, cataracts, autism, and aging. The current study was perform to assay the antioxidant activity different fractions of methanolic extract of golden chanterelle mushroom Cantharellus cibarius, a mushroom found in the north of Iran. Different fractions of methanolic extract of this mushroom, including n-hexane, chloroform, ethyl acetate, n-butanol, and water, were evaluated for antioxidant activity using six in vitro assay systems. Mushroom fruit was obtained from the local market, Sari (northern Iran). The n-hexane fraction had higher amounts of flavonoids contents (40.01 ± 1.30 mg quercetin equivalent g-1 of extract) and the highest exhibition of nitric oxide scavenging activity (77.21 ± 1.48%). The highest content of phenol was observed in the n-butanol fraction, which was 40.97 ± 0.99 mg gallic acid equivalent g-1 of extract. Among all the fractions, the ethyl acetate fraction was found to show higher DPPH scavenging activity (33.43 ± 1.30%) and the aqueous fraction to display the most reducing power. The highest Fe2+ chelating activity was observed in the chloroform fraction and then in the n-hexane fraction (86.13 ± 1.61 and 80.68 ± 2.07, respectively). The results all together signify C. cibarius as a valuable source of natural bioactive compounds with antioxidant activity.
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10.1615/intjmedmushrooms.v17.i6.60
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pubmed_294_18715
|
We describe molecular genetic findings in a patient who initially presented with an intermediate teratoma of the testis and who many years later presented with an oligodendro-astrocytoma. In addition he developed a malignant histiocytoma over the scapula, an adenocarcinoma of the stomach and a late stage adenoma of the sigmoid colon. Due to the development of several neoplasms the possibility of either ataxia telangiectasia or Li-Fraumeni syndrome was considered in differential diagnosis. A molecular genetic investigation revealed that both he and his brother carried a germline p53 tumor suppressor gene mutation at codon 248. From this result we conclude that this family belongs to the Li-Fraumeni syndrome. Once characterized as belonging to the Li-Fraumeni syndrome, the remaining members of the family were typed to determine if they too carried the same mutation. The two children of the index patient were shown not to carry the mutation and are therefore at no increased risk of developing any of the Li-Fraumeni spectrum of malignancies. A molecular genetic investigation into similar families could help to prevent the development of additional malignancies as seen in the index patient, as radiotherapy may interfere with the normal function of the p53 protein and this may in turn help to orchestrate DNA repair after radiation.
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pubmed_294_18715
|
pubmed_149_7126
|
OBJECTIVE
The objective of this study was to assess current Cochrane Review practice in identifying and incorporating information from clinical trial registers.
STUDY DESIGN AND SETTING
A cross-sectional study was conducted to assess a sample of new or updated intervention reviews from all Cochrane Review Groups up to February 1, 2017. Two assessors independently extracted data from each review using a pretested audit questionnaire. Data were analyzed relating to the frequency of reporting (1) the register source and search strategy; (2) the results of trial register searches; and (3) the use of trial register information in the review.
RESULTS
Over 90% (236/260) of Cochrane Reviews reported searching a trial register (e.g., ClinicalTrials.gov or the WHO International Clinical Trials Registry Platform). In reviews that reported trial register searches, 39% (92/236) indicated the number of trial records retrieved and 56.8% (134/236) used information from the trial register records in the review. Trial record information was incorporated into the results (39.6%; 53/134), risk of bias assessments (53.7%; 72/134), and discussion (24.6%, 33/134) and conclusion sections (25.4%, 34/134).
CONCLUSION
Most audited reviews used trial register information. Guidance may be needed to better incorporate information from these valuable resources in Cochrane Reviews to assist future research decisions made by funders and prospective study investigators.
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10.1016/j.jclinepi.2019.05.020
|
pubmed_200_6026
|
BACKGROUND
Given the rapid increase of Internet use for effective health communication, it is important for health practitioners to be able to identify and mobilize active users of online health information across various web-based health intervention programmes. We propose the concept 'health e-mavens' to characterize individuals actively engaged in online health information seeking and sharing activities.
OBJECTIVES
This study aimed to address three goals: (i) to test the factor structure of health e-mavenism, (ii) to assess the reliability and validity of this construct and (iii) to determine what predictors are associated with health e-mavenism.
METHODS
This study was a secondary analysis of nationally representative data from the 2010 Health Tracking Survey. We assessed the factor structure of health e-mavenism using confirmatory factor analysis and examined socio-demographic variables, health-related factors and use of technology as potential predictors of health e-mavenism through ordered regression analysis.
RESULTS
Confirmatory factor analyses showed that a second-order two-factor structure best captured the health e-maven construct. Health e-mavenism comprised two second-order factors, each encompassing two first-order dimensions: information acquisition (consisting of information tracking and consulting) and information transmission (consisting of information posting and sharing). Both first-order and second-order factors exhibited good reliabilities. Several factors were found to be significant predictors of health e-mavenism.
DISCUSSION AND CONCLUSION
This study offers a starting point for further inquiries about health e-mavens. It is a fruitful construct for health promotion research in the age of new media technologies. We conclude with specific recommendations to further develop the health e-maven concept through continued empirical research.
|
10.1111/hex.12398
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pubmed_312_19317
|
Tropomyosin (TM) exists in thermal equilibrium between a highly structured N state, a partially unfolded X state, and a completely unfolded D state, i.e., N in equilibrium X in equilibrium D. The strongly immobilized electron spin resonance (ESR) spectral component of spin-labeled TM corresponds to TM in the N state and the weakly immobilized component to TM in the X state below the main unfolding transition and to TM in the D state above this transition [Graceffa, P., & Lehrer, S. S. (1984) Biochemistry 23, 2606-2612]. The addition of actin, troponin (TN), and heavy meromyosin (HMM) to spin-labeled TM reduces the ratio of weakly to strongly immobilized labels, indicating a shift in the N in equilibrium X in equilibrium D equilibrium toward the N state. At 37 degrees C, for spin-labeled TM alone K (=X/N) greater than 1.0 with some TM in the D state, K = 0.8 for spin-labeled TM bound to actin, and K less than 0.05 for spin-labeled TM bound to actin + TN +/- Ca2+, actin + HMM + TN +/- Ca2+, and actin + HMM. Thus, actin + TN dramatically shifts the TM structure to the N conformation with little further effect upon addition of Ca2+ or HMM. The temperature at which spin-labeled TM begins to dissociate from a protein complex was determined from the temperature dependence of the ESR spectra.(ABSTRACT TRUNCATED AT 250 WORDS)
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10.1021/bi00332a022
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pubmed_724_8226
|
BACKGROUND
Impaired face processing is a widely documented deficit in autism. Although the origin of this deficit is unclear, several groups have suggested that a lack of perceptual expertise is contributory. We investigated whether individuals with autism develop expertise in visuoperceptual processing of faces and whether any deficiency in such processing is specific to faces, or extends to other objects, too.
METHOD
Participants performed perceptual discrimination tasks, including a face inversion task and a classification-level task, which requires especially fine-grained discriminations, on three classes of stimuli: socially-laden faces, perceptually homogenous novel objects, greebles, and perceptually heterogeneous common objects.
RESULTS
We found that children with autism develop typical levels of expertise for recognition of common objects. However, they evince poorer recognition for perceptually homogenous objects, including faces and, most especially, greebles.
CONCLUSIONS
Documenting the atypical recognition abilities for greebles in children with autism has provided an important insight into the potential origin of the relatively poor face recognition skills. Our findings suggest that, throughout development, individuals with autism have a generalized deficit in visuoperceptual processing that may interfere with their ability to undertake configural processing, and that this, in turn, adversely impacts their recognition of within-class perceptually homogenous objects.
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10.1111/j.1469-7610.2008.01903.x
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pubmed_870_127
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Sera from rats bearing primary or grafted colon carcinoma may contain antibodies that can react with antigenic determinants at the surface of cultivated colon cancer cells. Assays with various target cells and absorption experiments suggest that antigens recognized by circulating antibodies are common to independent lines of cultivated colon cancer cells. They are therefore cross-reacting, tumor-type-specific antigens. They could be embryonic or fetal antigens, because some sera from multiparous animals react with colon cancer cells. However, blocking experiments suggest that these antigens differ from the carcinofetal antigen previously demonstrated on the surface of intestinal cancer cells by xenoantiserum.
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pubmed_870_127
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pubmed_113_11727
|
BACKGROUND
Right ventricular function is strongly associated with clinical outcomes in populations at high cardiovascular risk. Renal Transplant Recipients have multiple coexisting comorbidities potentially involved in the biventricular dysfunction including the right ventricular chamber. Speckle tracking echocardiography is recently used to investigate the normal function of this chamber. The study aims to verify whether global longitudinal strain carries clinical and prognosis implications in the renal transplant recipients during 1 year of regular unsupervised physical activity and compared to a control group.
METHODS
A group of 50 transplant recipients, aged 49.6±11.5 was submitted for 1 year to a moderate intensity of mixed exercise. All the subjects were followed by echocardiographic exam every 6 months, only 25 subjects with a high quality of image were investigated by 2D Speckle tracking strain analysis with the measurement calculated at T0, T6, and T12 months.
RESULTS
Renal transplant recipients started with low values of right ventricle global longitudinal strain compared to health controls; it increased significantly (P<0.01) after 12 months of exercise, restoring the normal range.
CONCLUSIONS
Moderate intensity of physical exercise, despite unsupervised, support a normal RV ventricular performance in renal transplant recipients' strain analysis contribute to plan a correct follow-up, with prognostic impact in these patients practicing physical exercise.
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10.23736/S0022-4707.21.12537-X
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pubmed_157_23165
|
The desire for power and social dominance plays a significant role in the development of social aggression. Although the construct of Machiavellianism reflects these aspects well, it has hardly been recognized in Germany. In this review article the construct of Machiavellianism will be presented. Previous research on the relationship between Machiavellianism and particularly aggressive behavior in children and adolescents are critically discussed and implications for future studies are derived.
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10.1024/1422-4917/a000395
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pubmed_235_11954
|
PURPOSE
The aim of this study was to report outcomes following mini-open lower limb fasciotomy (MLLF) in active adults with chronic exertional compartment syndrome (CECS).
METHODS
From 2013-2018, 38 consecutive patients (mean age 31 years [16-60], 71% [n = 27/38] male) underwent MLLF. There were 21 unilateral procedures, 10 simultaneous bilateral and 7 staged bilateral. There were 22 anterior fasciotomies, five posterior and 11 four-compartment. Early complications were determined from medical records of 37/38 patients (97%) at a mean of four months (1-19). Patient-reported outcomes (including EuroQol scores [EQ-5D/EQ-VAS], return to sport and satisfaction) were obtained via postal survey from 27/38 respondents (71%) at a mean of 3.7 years (0.3-6.4).
RESULTS
Complications occurred in 16% (n = 6/37): superficial infection (11%, n = 4/37), deep infection (3%, n = 1/37) and wound dehiscence (3%, n = 1/37). Eight per cent (n = 3/37) required revision fasciotomy for recurrent leg pain. At longer-term follow-up, 30% (n = 8/27) were asymptomatic and another 56% (n = 15/27) reported improved symptoms. The mean pain score improved from 6.1 to 2.5 during normal activity and 9.1 to 4.7 during sport (both p < 0.001). The mean EQ-5D was 0.781 (0.130-1) and EQ-VAS 77 (33-95). Of 25 patients playing sport preoperatively, 64% (n = 16/25) returned, 75% (n = 12/16) reporting improved exercise tolerance. Seventy-four per cent (n = 20/27) were satisfied and 81% (n = 22/27) would recommend the procedure.
CONCLUSION
MLLF is safe and effective for active adults with CECS. The revision rate is low, and although recurrent symptoms are common most achieve symptomatic improvement, with reduced activity-related leg pain and good health-related quality of life. The majority return to sport and are satisfied with their outcome.
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10.1007/s00590-021-02919-z
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pubmed_419_24110
|
BACKGROUND AND OBJECTIVE
In the last few decades, several studies have been performed to investigate traumatic brain injuries (TBIs) and to understand the biomechanical response of brain tissues, by using experimental and computational approaches. As part of computational approaches, human head finite element (FE) models show to be important tools in the analysis of TBIs, making it possible to estimate local mechanical effects on brain tissue for different accident scenarios. The present study aims to contribute to the computational approach by means of the development of three advanced FE head models for accurately describing the head tissue dynamics, the first step to predict TBIs.
METHODS
We have developed three detailed FE models of human heads from magnetic resonance images of three volunteers: an adult female (32 yrs), an adult male (35 yrs), and a young male (16 yrs). These models have been validated against experimental data of post mortem human subjects (PMHS) tests available in the literature. Brain tissue displacements relative to the skull, hydrostatic intracranial pressure, and head acceleration have been used as the parameters to compare the model response with the experimental response for validation. The software CORAplus (CORrelation and Analysis) has been adopted to evaluate the bio-fidelity level of FE models.
RESULTS
Numerical results from the three models agree with experimental data. FE models presented in this study show a good bio-fidelity for hydrostatic pressure (CORA score of 0.776) and a fair bio-fidelity brain tissue displacements relative to the skull (CORA score of 0.443 and 0.535). The comparison among numerical simulations carried out with the three models shows negligible differences in the mechanical state of brain tissue due to the different morphometry of the heads, when the same acceleration history is considered.
CONCLUSIONS
The three FE models, thanks to their accurate description of anatomical morphology and to their bio-fidelity, can be useful tools to investigate brain mechanics due to different impact scenarios. Therefore, they can be used for different purposes, such as the investigation of the correlation between head acceleration and tissue damage, or the effectiveness of helmet designs. This work does not address the issue to define injury thresholds for the proposed models.
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10.1016/j.cmpb.2022.107225
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pubmed_614_10373
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Cutaneous anaplastic large cell lymphoma can present either as a primary disease or as secondary to a pre-existing systemic anaplastic lymphoma. Distinguishing primary cutaneous anaplastic lymphoma (PC-ALCL) from its systemic counterpart requires a complete clinical and laboratory workup. We hereby report a case of PC-ALCL in a young adult, who presented with unusual rapidly progressive ulcerated mass in the neck. Biopsy showed anaplastic large cells, which were strongly positive for CD30 and CD25 but ALK1 gene product was negative. Clinical examination and computed tomography (CT) scan ruled out extracutaneous involvement. Chemotherapy with 6 cycles of CHOP regimen was planned and on follow-up, a complete remission of the lesion was attained.
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10.4103/0973-1482.139338
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pubmed_859_16745
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Hydrops fetalis is a rare disorder associated with significant perinatal complications and a high perinatal mortality of at least 50%. Nonimmune hydrops fetalis (NIHF) is more frequent and results from a wide variety of etiologies. One cause of NIHF is lymphatic malformation 6 (LMPHM6) due to biallelic loss-of-function (LoF) variants in PIEZO1. Most individuals are diagnosed postnatally and only few clinical data are available on fetal presentations. We report six novel biallelic predicted LoF variants in PIEZO1 identified by exome sequencing in six fetuses and one deceased neonate from four unrelated families affected with LMPHM6. During the pregnancy, most cases are revealed by isolated NIHF at second trimester of gestation. At post-mortem examination ascites, pleural effusions and telengectasies can guide the etiological diagnosis. We aim to further describe the perinatal presentation of this condition which could be underdiagnosed. This article is protected by copyright. All rights reserved.
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10.1111/cge.14274
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pubmed_997_6945
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Since the advent of sequencing technologies in the 1990s, researchers have focused on the association between aberrations in chromosomal DNA and disease. However, not all forms of the DNA are linear and chromosomal. Extrachromosomal circular DNAs (eccDNAs) are double-stranded, closed-circled DNA constructs free from the chromosome that reside in the nuclei. Although widely overlooked, the eccDNAs have recently gained attention for their potential roles in physiological response, intratumoral heterogeneity and cancer therapeutics. In this review, we summarize the history, classifications, biogenesis, and highlight recent progresses on the emerging topic of eccDNAs and comment on their potential application as biomarkers in clinical settings.
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10.1016/j.csbj.2022.10.033
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pubmed_320_6292
|
OBJECTIVE
We attempted to obtain baseline data on the incidence of intussusception and its association with gastroenteritis in a cross-sectional observational study in children.
METHODS
Admissions to all 38 pediatric units in Switzerland because of intussusception were reported to the Swiss Pediatric Surveillance Unit from April 2003 to March 2006. Patient and disease characteristics were assessed prospectively with the use of a standardized questionnaire based on the case definition for intussusception developed by the Brighton Collaboration. Completeness of reporting was verified through capture-recapture analysis.
RESULTS
There were 294 patients with reported intussusception; 35 cases were excluded for various reasons, and 29 additional patients were identified through International Classification of Diseases, 10th Revision, codes. After capture-recapture analysis, we estimated underreporting to the Swiss Pediatric Surveillance Unit to be 32% and we calculated a true number of 381 intussusception episodes. The highest level of diagnostic certainty was reached by 248 patients, and 20 fulfilled level 2 criteria; for the remaining 20 patients, available information was insufficient. The mean age of the patients was 2.7 years. The yearly mean incidence of intussusception was 38, 31, and 26 cases per 100,000 live births in the first, second, and third year of life, respectively, with no apparent seasonality. Seventy patients had a history of coinciding gastroenteritis, and 5 of 61 tested positive for rotavirus. Spontaneous devagination was observed for 38 patients; enemas reduced intussusception successfully in 183 cases, whereas surgical treatment was required in 67. All patients recovered without sequelae.
CONCLUSIONS
This is the first prospective nationwide surveillance of intussusception in childhood using a standardized case definition. Most cases occurred beyond infancy, and association with rotavirus gastroenteritis was rare.
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10.1542/peds.2007-0035
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pubmed_592_1384
|
Ferrets were tested for their ability to detect temporal gaps in noise before and after bilateral lesions of the primary auditory cortex. Thresholds for gap detection were determined first for normal animals with band-pass noises at various center frequencies (0.5 to 32 kHz) and at 8 kHz with various sound pressure levels (-10-70 dB). Gap-detection ability improved steadily as sound pressure increased up to 70 dB. No systematic relation was found between threshold and center frequency. To determine the effects of brain damage, ferrets were tested with 8-kHz band-pass noise at 70 dBSPL. After bilateral lesions of auditory cortex, ferrets were still capable of detecting gaps, but the mean threshold was elevated from 10.1 to 20.1 ms. The data demonstrate that auditory cortex is important for perceptual tasks requiring fine temporal resolution.
|
10.1037//0735-7044.110.3.542
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pubmed_814_12761
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Hosting millions of microorganisms, the digestive tract is the primary and most important part of bacterial colonization. On one side, in cases of opportunistic invasion, the abundant bacterial population inside intestinal tissues may face potential health problems such as inflammation and infections. Therefore, the immune system has evolved to sustain the host-microbiota symbiotic relationship. On the other hand, to maintain host immune homeostasis, the intestinal microflora often exerts an immunoregulatory function that cannot be ignored. A field of great interest is the association of either microbiota or probiotics with the immune system concerning clinical uses. This microbial community regulates some of the host's metabolic and physiological functions and drives early-life immune system maturation, contributing to their homeostasis throughout life. Changes in gut microbiota can occur through modification in function, composition (dysbiosis), or microbiota-host interplays. Studies on animals and humans show that probiotics can have a pivotal effect on the modulation of immune and inflammatory mechanisms; however, the precise mechanisms have not yet been well defined. Diet, age, BMI (body mass index), medications, and stress may confound the benefits of probiotic intake. In addition to host gut functions (permeability and physiology), all these agents have profound implications for the gut microbiome composition. The use of probiotics could improve the gut microbial population, increase mucus-secretion, and prevent the destruction of tight junction proteins by decreasing the number of lipopolysaccharides (LPSs). When LPS binds endothelial cells to toll-like receptors (TLR 2, 4), dendritic cells and macrophage cells are activated, and inflammatory markers are increased. Furthermore, a decrease in gut dysbiosis and intestinal leakage after probiotic therapy may minimize the development of inflammatory biomarkers and blunt unnecessary activation of the immune system. In turn, probiotics improve the differentiation of T-cells against Th2 and development of Th2 cytokines such as IL-4 and IL-10. The present narrative review explores the interactions between gut microflora/probiotics and the immune system starting from the general perspective of a biological plausibility to get to the in vitro and in vivo demonstrations of a probiotic-based approach up to the possible uses for novel therapeutic strategies.
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10.3389/fimmu.2021.578386
|
pubmed_639_4086
|
BACKGROUND
Despite the rise in positive psychology within organisational settings, less is known about the positive factors associated with veterinary work and veterinarian well-being. This qualitative study investigated sources of pleasure for veterinarians.
METHOD
A subset of archival data from a larger study on veterinary well-being was analysed. The current study was based on data from 273 veterinarians responding to a Ten Statements Test (TST) and demographic questions. In the TST, participants provided up to 10 responses to the prompt, 'I derive pleasure in my work as a veterinarian when…'.
RESULTS
Using the job demands-resources model as a framework, a total of 2536 responses were manually coded into themes relating to resources (positive responses) or demands (responses indicating a negative factor). In order of frequency, job resources are related to professional expertise (22%), positive outcomes (20%), job characteristics (19%), relationships (16%), recognition (10%), helping (7%) and personal resources (3%). Top job demands are related to stress and fatigue (17%) and poor work-life balance (16%).
CONCLUSION
The results suggest that there are an abundance of positive factors in veterinary work associated with feelings of pleasure, which may support veterinarian well-being.
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10.1002/vetr.54
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pubmed_687_25585
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Noise pollution is a severe public health problem as continuous exposure to even moderate noise levels between 55-65 dB can lead to various pathologies, including neurological states. In the present study, we assessed the ultrastructural alterations in selective auditory pathways of the rat brain following high intensity white noise exposure. In addition, learning, anxiety-like behavior and locomotor activity were assessed. Adult male rats were exposed to 100 dB noise, one hour daily, for 10 consecutive days. The evaluations were performed on day 11. Exposure to noise did not affect learning or the components of locomotor activity. However, it induced anxiety-like behavior as evidenced by time spent in the closed arm of elevated-plus maze. Concomitantly, ultrastructural changes in medial geniculate body, considered an integral component of classical auditory pathway, as well as in the hippocampus and basolateral amygdala, considered important structures of non-classical auditory pathway were noted. Specifically, noise resulted in neuronal apoptosis, chromatolysis, cytoplasmic organelle destruction, and glial activation in medial geniculate body and hippocampus, as well as mild alterations in amygdala. These results provide further evidence of detrimental consequences following exposure to loud noise.
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10.1016/j.neulet.2020.134898
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pubmed_632_15142
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Soil fluoride (F) and cadmium (Cd) pollution are of great concern in recently years, due to the fact that considerable amounts of wastewater, gas and residue, containing F and Cd, have been discharged into the environment through ore smelting. Soil F and Cd contamination may result in their interaction in soil and plant, which affects their fractionation distribution in soil and accumulation in oilseed rape. Oilseed rape, which is widely planted and consumed as a popular vegetable in arid and semi-arid land of northwest China, has been believed to a hyperaccumulator for Cd. However, there is limited information about the accumulation, interaction and fractionation of F and Cd in soil-oilseed rape system under F-Cd stresses. A pot-culture experiment, with single (F or Cd) or double elements (F-Cd) being added to soil, was carried out study the accumulation, interaction and fractionation of F and Cd in sierozem and oilseed rape. We found that soil F applications increased the contents of Cd in exchangeable fraction (EX-Cd), the bound to carbonate fraction (CAB-Cd) and the bound to iron and manganese oxides fraction (FMO-Cd) in soil and also increased plant Cd accumulation. Therefore, we suggest that the permitted level of F should be confined within soil quality standards for farmland of China in order to upset the effect of high F concentration on bioavailability of soil Cd. However, soil Cd applications showed negative effects on the content of F in water soluble fraction (Water-F), hence decreased plant F accumulation. A better understanding of the accumulation, interaction and fractionation of F and Cd in sierozem-oilseed rape system are of great importance for environmental protection and for human health. The present study may serve as a basic understanding of the accumulation, interaction and fractionation of F and Cd in sierozem-oilseed rape system, and provide a suggestion for the environmental management.
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10.1016/j.plaphy.2018.04.017
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pubmed_692_11765
|
Dynamic reporting tools, such as dashboards, should be developed to measure emergency department (ED) performance. However, choosing an effective balanced set of performance measures and key performance indicators (KPIs) is a main challenge to accomplish this. The aim of this study was to develop a balanced set of KPIs for use in ED strategic dashboards following an analytic hierarchical process. The study was carried out in 2 phases: constructing ED performance measures based on balanced scorecard perspectives and incorporating them into analytic hierarchical process framework to select the final KPIs. The respondents placed most importance on ED internal processes perspective especially on measures related to timeliness and accessibility of care in ED. Some measures from financial, customer, and learning and growth perspectives were also selected as other top KPIs. Measures of care effectiveness and care safety were placed as the next priorities too. The respondents placed least importance on disease-/condition-specific "time to" measures. The methodology can be presented as a reference model for development of KPIs in various performance related areas based on a consistent and fair approach. Dashboards that are designed based on such a balanced set of KPIs will help to establish comprehensive performance measurements and fair benchmarks and comparisons.
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10.1097/HCM.0000000000000033
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pubmed_716_7653
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The ongoing COVID-19 pandemic has taken a heavy toll on the physical and mental health of the public. Nevertheless, the presence of green and blue spaces has been shown to be able to encourage physical activities and alleviate the mental distress caused by COVID-19. However, just as the impact of COVID-19 varies by geographical region and area, the distribution of green and blue spaces is also different across different neighborhoods and areas. By using Hong Kong as the study area, we determine the local neighborhoods that suffer from both high COVID-19 infection risk as well as low green and blue space accessibility. The results show that some of the poorest neighborhoods in the territory such as Sham Shui Po, Kwun Tong and Wong Tai Sin are also among the most doubly disadvantaged in terms of COVID-19 infection risk as well as green and blue space accessibility.
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10.1371/journal.pone.0273125
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pubmed_130_6371
|
Data on the use of oral anti-coagulants (OAC) for stroke prevention in cancer patients with atrial fibrillation (AF) are sparse. Nationwide cohort study of patients with AF (2012-2018) and an indication for OAC who were diagnosed with cancer at least one year later (N = 12 756). We identified treatment with OAC at cancer diagnosis and the following year and described the incidence of discontinuing or switching between warfarin and direct oral anti-coagulants (DOACs). We also described baseline characteristics associated with OAC non-persistence. One third of the cancer patients received no OAC therapy, whereas 42% received warfarin and 24% received DOAC treatment. Switching incidence between OACs was higher for those receiving warfarin treatment (8.6%) than DOAC treatment (1.7%) within one year. Treatment discontinuation was 61% for warfarin and 26% for DOAC. Females were less likely to discontinue DOAC than males (ratio 0.77, 95% confidence interval: 0.66, 0.90). Increasing cancer stage was associated with discontinuation of DOAC, but not warfarin. OAC for stroke prevention in AF was used by two thirds of patients with newly diagnosed cancer. Switching between OACs and discontinuation was more common for warfarin than DOAC, and females had higher persistence with DOACs.
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10.1111/bjh.18060
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pubmed_1115_6684
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Methylglyoxal (MG) is one of the most powerful glycating agents of proteins and other important cellular components and has been shown to be toxic to cultured cells. Under hyperglycaemic conditions, an increase in the concentration of MG has been observed in human body fluids and tissues that seems to be responsible for diabetic complications. Recent data suggest that diabetes may cause impairment of cognitive processes, according to a mechanism involving both oxidative stress and advanced glycation end product (AGE) formation. In this work, we explored the molecular mechanism underlying MG toxicity in neural cells, by investigating the effect of MG on both the interleukin-1beta (IL-1beta), as the major inducer of the acute phase response, and the nervous growth factor (NGF) expression. Experiments were performed on cultured neural cells from rat hippocampus, being this brain region mostly involved in cognitive processes and, therefore, possible target of diabetes-mediated impairment of cognitive abilities. Results show that MG treatment causes in hippocampal neural cells extensive, oxidative stress-mediated cell death, in consequence of a strong catalase enzymatic activity and protein inhibition. MG also causes a very significant increase in both transcript and protein expression of the NGF as well as of the pro-inflammatory cytokine IL-1beta. MG co-treatment with the antioxidant N-acetylcysteine (NAC) completely abrogates the observed effects. Taken together, these data demonstrate that hippocampal neurons are strongly susceptible to MG-mediated oxidative stress.
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10.1016/j.brainres.2004.01.066
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pubmed_72_16408
|
OBJECTIVE
Although physical exercise is the commonly recommended for osteoarthritis (OA) patients, the working mechanism behind the positive effects of physical exercise on pain and function is a black box phenomenon. In the present study we aimed to identify possible mediators in the relation between physical exercise and improvements of pain and function in OA patients.
DESIGN
A systematic search for all studies evaluating the effects of physical exercise in OA patients and select those that additionally reported the change in any physiological factor from pre-to post-exercise.
RESULTS
In total, 94 studies evaluating 112 intervention groups were included. Most included studies evaluated subjects with solely knee OA (96 out of 112 groups). Based on the measured physiological factors within the included studies, 12 categories of possible mediators were formed. Muscle strength and ROM/flexibility were the most measured categories of possible mediators with 61 and 21 intervention groups measuring one or more physiological factors within these categories, respectively. 60% (31 out of 52) of the studies showed a significant increase in knee extensor muscle strength and 71% (22 out of 31) in knee flexor muscle strength over the intervention period. All 5 studies evaluating extension impairments and 10 out of 12 studies (83%) measuring proprioception found a significant change from pre-to post-intervention.
CONCLUSION
An increase of upper leg strength, a decrease of extension impairments and improvement in proprioception were identified as possible mediators in the positive association between physical exercise and OA symptoms.
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pubmed_72_16408
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pubmed_234_22027
|
In this study, we examined in detail the interaction of platelet factor-4 (PF-4) with fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF) and the effect of PF-4-derived synthetic peptides. We show that a peptide between amino acids 47 and 70 that contains the heparin-binding lysine-rich site inhibits FGF-2 or VEGF function. This is based on the following observations: PF-4 peptide 47-70 inhibited FGF-2 or VEGF binding to endothelial cells; it inhibited FGF-2 or VEGF binding to FGFRs or VEGFRs in heparan sulfate-deficient CHO cells transfected with FGFR1 (CHOFGFR1) or VEGFR2 (CHOmVEGFR2) cDNA; it blocked proliferation or tube formation in three-dimensional angiogenesis assays; and, finally, it competed with the direct association of (125)I-PF-4 with FGF-2 or VEGF, respectively, and inhibited heparin-induced FGF-2 dimerization. A shorter C-terminal peptide (peptide 58-70), which still contained the heparin-binding lysin-rich site, had no effect. Peptide 17-58, which is located in the central part of the molecule, although it does not inhibit FGF-2 or VEGF binding or biologic activity in endothelial cells, inhibited heparin-dependent binding of (125)I-FGF-2 or (125)I-VEGF to CHOmFGFR1 or CHOmVEGFR2 cells, respectively. Shorter peptides (peptides 34-58 and 47-58) did not show any of these effects.
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pubmed_234_22027
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pubmed_932_14389
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Taking advantage of ultrahigh electric field generated in electric-double-layer transistors (EDLTs), we investigated spin-orbit interaction (SOI) and its modulation in epitaxial trilayer graphene. It was found in magnetotransport that the dephasing length L(φ) and spin relaxation length L(so) of carriers can be effectively modulated with gate bias. As a direct result, SOI-induced weak antilocalization (WAL), together with a crossover from WAL to weak localization (WL), was observed at near-zero magnetic field. Interestingly, among existing localization models, only the Iordanskii-Lyanda-Geller-Pikus theory can successfully reproduce the obtained magnetoconductance well, serving as evidence for gate tuning of the weak but distinct SOI in graphene. Realization of SOI and its large tunability in the trilayer graphene EDLTs provides us with a possibility to electrically manipulate spin precession in graphene systems without ferromagnetics.
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10.1021/nl204012c
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pubmed_1082_20125
|
We have examined the interactions of 5-aminosalicylic acid with nitric oxide (NO). Phenylephrine-precontracted rat aortic strips with intact endothelium were further contracted by 5-aminosalicylic acid (50-200 microM) in a concentration-dependent manner. Removal of endothelium, inhibition of guanylate cyclase by methylene blue, inhibition of NO biosynthesis by NG-nitro-L-arginine as well as in inactivation of NO by oxyhemoglobin abolished the effect of 5-aminosalicylic acid. The antiaggregatory effects of 3-morpholinosydnonimine and rat peritoneal neutrophils, which are due to release of NO, were diminished in a concentration-dependent manner by 5-aminosalicylic acid (50-250 microM). In both experimental models the effects of 5-aminosalicylic acid were significantly reduced by superoxide dismutase in a concentration which alone exhibited no effect. Since NO might act as a cytotoxic and vasodilating mediator, our results suggest that inactivation of NO by 5-aminosalicylic acid could contribute to the therapeutic activity of the drug in inflammatory bowel disease.
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10.1016/0014-2999(95)00305-5
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pubmed_828_14522
|
Aboriginal boys of Chukotka and North-Evenk district of Magadan region aged 10-17 years were studied in 2004-2007 to characterize major and detailed indices of physical development and to evaluate the puberty stages (PS) according to J. Tanner. The body proportions and component content were found to depend on the region of habitation, degree of mestization and social conditions. Chukotka aboriginal boys were characterized by an increased body fat mass during the puberal period and a longitudinal body growth. In aboriginal boys of Russia's North-East in 2nd PS, the maximal increment was found in the indices of pelvic and shoulder width. In 3rd PS, the maximal increment was found in body mass, muscle and bone components, body length, body surface area, chest circumference, while the maximal increment in body fat mass was detected in 4th PS. Transformation of the increments of body parts and body mass components during the pubescence forms an adaptive type in an aboriginal, with the maximal changes at the stage of gonadal maturation, while the metabolic processes and mestization influence the formation of body proportions and components.
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pubmed_828_14522
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pubmed_778_23068
|
PURPOSE
Vietnamese children's performance on language-based processing tasks of fast-mapping (FM) word-learning and dynamic assessment (DA) word- and rule-learning tasks were investigated.
METHOD
Twenty-one first- and second-generation Vietnamese preschool children participated in this study. All children were enrolled in 2 Head Start programs in a large city in the Midwest. All children had passed a developmental assessment and routine speech, language, and hearing screenings. All participants were taught 4 invented monosyllabic words in an FM word task, an invented monosyllabic suffix rule (-po) meaning "a part of" in a DA rule task, and 4 invented bisyllabic words in a DA word task. Potential relationships among task performances were investigated. Receptive task performances, expressive task performances, and task totals were added to create receptive total, expressive total, and accumulated performance total (APT) scores. Relationships among receptive total, expressive total, and APT scores were also investigated.
RESULTS
Significant correlations were found between FM word, DA rule, and the receptive total. The expressive total correlated with all task total scores, APT, age, and modifiability scores. Modifiability scores correlated with the two DA tasks, expressive total, and the APT. Findings indicate that FM word and the expressive total were positively correlated with most of the other tasks, composite totals, and age.
CLINICAL IMPLICATIONS
Performance on language-based processing tasks may provide valuable information for separating typically developing Vietnamese preschool children from their peers with language disorders. Practitioners should consider linguistic characteristics of target stimuli. Comparisons should include task, receptive, expressive, and APT.
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10.1044/0161-1461(2005/023)
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pubmed_918_19000
|
Bacterial RNA polymerase employs extra-cytoplasmic function (ECF) σ factors to regulate context-specific gene expression programs. Despite being the most abundant and divergent σ factor class, the structural basis of ECF σ factor-mediated transcription initiation remains unknown. Here, we determine a crystal structure of Mycobacterium tuberculosis (Mtb) RNAP holoenzyme comprising an RNAP core enzyme and the ECF σ factor σH (σH-RNAP) at 2.7 Å, and solve another crystal structure of a transcription initiation complex of Mtb σH-RNAP (σH-RPo) comprising promoter DNA and an RNA primer at 2.8 Å. The two structures together reveal the interactions between σH and RNAP that are essential for σH-RNAP holoenzyme assembly as well as the interactions between σH-RNAP and promoter DNA responsible for stringent promoter recognition and for promoter unwinding. Our study establishes that ECF σ factors and primary σ factors employ distinct mechanisms for promoter recognition and for promoter unwinding.
|
10.1038/s41467-019-09096-y
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pubmed_538_12886
|
The quantified analysis of the electroencephalogram (qEEG) has enabled the extraction of additional psychophysiological information from the raw EEG, but in turn has introduced a number of distortions. This study compared Dynamic Spectral Analysis (DSA), a novel and mathematically stringent technique for the evaluation of qEEG activity with conventional power spectral analysis in subjects with both first episode and chronic schizophrenia and matched controls. Advantages of the technique in the automated processing of data, rejection of artefact, avoidance of artefact introduced by the mathematical trans-formation of the data and the identification of irregular low frequency artefactual activity "pi" are discussed in detail. Using this method, the study has confirmed past observations of increased slow wave activity in schizophrenia, and identified a decrease in peak frequency in the alpha band in the subjects with chronic schizophrenia. The two clinical groups differed in mean peak frequency in the delta band with the first episode schizophrenia subjects having a raised mean peak frequency and the subjects with chronic schizophrenia having a lowered mean peak frequency. The results suggest continued change in the EEG with illness chronicity in schizophrenia. These changes were most evident in the frequency domain emphasizing the importance of routine measurement of mean band frequencies in qEEG studies.
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10.1080/00207450500402977
|
pubmed_289_18703
|
Severe pre-eclampsia and eclampsia are common causes of maternal deaths worldwide and more so in developing countries. Magnesium sulphate (MgSO4) is now the most-recommended drug of choice to treat these conditions. Despite favourable policies for the use of MgSO4 treatment in India, eclampsia continues to take a high toll. This study examined the availability and use of MgSO4 treatment in the public health system and poor women's recent experiences with eclampsia treatment in Maharashtra state. A mix of qualitative and quantative methods was used. A facility-based survey of all secondary and tertiary healthcare facilities (n = 44) in 3 selected districts and interviews with public and contracted-in private sector obstetricians, health officials, and programme managers were conducted. A list of recently-delivering women from marginalized communities, with up to two livebirths, was drawn through a community-level survey in 272 villages covered by 60 subcentres selected at random. Mothers were selected for interviews, using maximum variation sampling, and interviews were conducted with 17% of the mothers who reported having experienced eclampsia; 61% of facilities had no stock of MgSO4, the stock-out position continuing from a period ranging from 3 months to 3 years while another 20% had some stock, although less than the expected minimum quantity. No treatment for eclampsia was provided in the recent 3 months at 73% facilities. Our survey of recently-delivering mothers recorded a history of eclampsia in 3.2% pregnancies/ deliveries. Interviews with 10 such mothers revealed that treatment for eclampsia has been sought from public as well as private hospitals and from traditional healers. However, facilities where women have received medical treatment are exclusively in the private sector. Almost all public and private care providers were aware of MgSO4 as the gold standard to treat eclampsia; however, it is unclear if they knew of its use to treat severe pre-eclampsia. The private care providers routinely used MgSO4 for eclampsia treatment while the public care providers seemed hesitant to use it fearing risks of complications. We stress the need for improved inventory control practices to ensure sustained availability of supplies and building confidence of care providers in using MgSO4 treatment for severe pre-eclampsia and eclampsia in public facilities, in addition to teaching expectant mothers how to recognize symptoms of these conditions.
|
10.3329/jhpn.v31i1.14753
|
pubmed_752_1316
|
Criteria to assess charge-transfer (CT) and CT-like character of electronic excitations are examined. Time-dependent density functional theory (TDDFT) calculations with non-hybrid, hybrid, and tuned long-range corrected (LC) functionals are compared with coupled-cluster (CC) benchmarks. The test set comprises an organic CT complex, two push-pull donor-acceptor chromophores, a cyanine dye, and several polycyclic aromatic hydrocarbons. Proper CT is easily identified. Excitations with significant density changes upon excitation within regions of close spatial proximity can also be diagnosed. For such excitations, the use of LC functionals in TDDFT sometimes leads to dramatic improvements of the singlet energies, similar to proper CT. It is shown that such CT-like excitations do not have the characteristics of physical charge transfer, and improvements with LC functionals may not be obtained for the right reasons. The TDDFT triplet excitation energies are underestimated for all systems, often severely. For the CT-like candidates, the singlet-triplet (S/T) separation changes from negative with a non-hybrid functional to positive with a tuned LC functional. For the cyanine, the S/T separation is systematically too large with TDDFT, leading to better error compensation for the singlet energy with a non-hybrid functional.
|
10.1021/acs.jctc.5b00335
|
pubmed_1039_16652
|
The growth-promoting effect of growth hormones and related polypeptides was examined in vitro with a clonogenic assay using human erythroleukemic cells (K562). The erythroleukemia cells were grown in a serum-substituted methylcellulose culture system and colonies counted after 4 days' incubation. Human growth hormone (hGH) was a potent stimulant for K562 cell growth (60% augmentation). The cys(Cam)53-hGH(1-134) fragment of hGH and human chorionic somatomammotropin had less than half the activity of the intact hGH molecule. Bovine growth hormone was inactive in enhancing K562 colony formation. K562 cell proliferation was stimulated by hGH at concentrations as low as 0.1 ng/ml. Insulin stimulated K562 cell proliferation most effectively at a concentration of 1 ng/ml. The K562 culture system may conveniently be employed for determining the in vitro bioactivity of hGH.
|
10.1210/jcem-51-5-1208
|
pubmed_469_1464
|
The development of high-frequency ultrasound made the diagnosis of pancreaticobiliary maljunction (PBM) possible. However, no study has been performed to clarify the sensitivity and specificity of transabdominal ultrasound (TAUS) in the diagnosis of PBM. The purpose of this study was to evaluate the accuracy of TAUS in the diagnosis of pediatric PBM and to assess factors that may influence the accuracy of ultrasound. This was a prospective study and 43 patients with suspected PBM were enrolled. All of these patients underwent TAUS examination to detect the pancreaticobiliary ductal union. Final diagnoses were determined by endoscopic retrograde cholangiopancreatography or intraoperative cholangiography. Sensitivity and specificity were calculated. Fisher exact test was used to analyze the difference of sonographic features between false-negative group and true-positive group. Transabdominal ultrasound demonstrated 77.4% (95% confidence interval, 58.5%-89.7%) sensitivity and 100% (95% confidence interval, 69.9%-100%) specificity for PMB diagnosis. In the false-negative group, infant patients (71.4% vs 16.7%, P = 0.012), cystic dilatation of the common bile duct (CBD) (71.4% vs 16.7%, P = 0.012), and stenosis of the distal CBD (71.4% vs 16.7%, P = 0.012) were more frequently observed than in the true-positive group. On the other hand, the true-positive group showed a higher incidence of protein plugs than the false-negative group (62.5% vs 0%, P = 0.007). Transabdominal ultrasound may serve as a potential alternative detection modality for pediatric patients with suspected PBM. Nondetection of the anomaly may be attributed to factors, such as younger age, cystic dilatation of the CBD, and stenosis of the distal CBD.
|
10.1097/RUQ.0000000000000585
|
pubmed_85_11014
|
OBJECTIVE
The aim of this study was to compare the diagnostic performance of Virtual Touch Tissue Imaging & Quantification (VTIQ) and Virtual Touch Tissue Quantification (VTQ) in differentiating benign from malignant thyroid nodules (TNs).
MATERIALS AND METHODS
In this study 107 TNs in 107 patients were enrolled and analyzed. All of them were detected by conventional ultrasound (US) and confirmed by fine-needle aspiration (FNA) biopsy or surgery. VTIQ and VTQ examinations were performed on each nodule. Thereafter the median and mean of shear wave speed (SWS) values in lesions on VTIQ and VTQ were computed (SWS-median and SWS-mean). With cytological results of FNA and histological results adopted as the reference standard, area under the receiver operating characteristic (AUROC) curve analysis was performed to evaluate the diagnostic efficiency of VTIQ and VTQ in differentiation of TNs.
RESULTS
Among the 107 lesions, 19 were papillary thyroid carcinomas (PTCs), 1 was medullary thyroid carcinoma (MTC) and 87 were benign. In total lesions, AUROC-median in VTIQ was significantly higher than that in VTQ (0.851 vs.0.759; p < 0.05).
CONCLUSION
VTIQ and VTQ were equivalent in diagnosing TNs when using SWS-mean, whereas VTIQ showed better performance in comparison with VTQ when using SWS-median.
|
10.3233/CH-16142
|
pubmed_937_19932
|
Beta-Agonists are a mainstay of asthma treatment. Short-acting beta-agonists are the most effective bronchodilators for rescue or quick relief of symptoms. Long-acting beta-agonists have a key role in long-term control when added to inhaled corticosteroid therapy, and are especially useful in the control of nocturnal asthma. Both types of beta-agonists may be used in the prophylaxis of exercise-induced asthma with long-acting beta-agonists providing more prolonged protection. beta-Agonists have minimal side effects and are safe when used appropriately.
|
10.1016/s0025-7125(02)00031-7
|
pubmed_293_11820
|
Disseminated histoplasmosis is an endemic systemic mycosis, caused by the dimorphic fungus Histoplasma capsulatum. The clinical manifestations depend on the inhaled fungal load, the immunological state of the patient and the virulence of the infecting fungal strain. The disseminated variant is most frequent in immunocompromised patients, with 90% of cases in patients with positive serology for HIV, In this series, 37 patients with diagnosis of HIV and disseminated histoplasmosis were evaluated. The 43.2% of the patients did not know their serology prior to the consultation due to histoplasmosis. The main clinical causes were impregnation syndrome (67.6%), fever (64.9%), respiratory symptoms (62.2%) and mucocutaneous manifestations (67.6%), among others. The 94.6% of the patients presented anemia, 75.7% had bicytopenia and 32.4% pancytopenia. The sensitivity of the blood cultures was 70.4%. The 86.5% of the patients did not have another opportunistic infection concomitant at the time of diagnosis. In 83.8% of patients, disseminated histoplasmosis was the first AIDS disease. A mortality of 14.7% was recorded.
|
10.4067/S0716-10182018000600671
|
pubmed_617_8062
|
A previous study found almost no leakage of polymeric nanomicelles from vessels in microtumors. If such vessels become leaky, sufficient nanomedicines may be delivered to microtumors and large tumors. To create leaky vessels, a combretastatin derivative (Cderiv), a vascular disrupting agent, was used. Via vital microscopy with fluorescein isothiocyanate (FITC)-labeled nanomicelles, the effect of Cderiv pretreatment on changes in micelle extravasation was investigated. Whether such treatment would prolong microtumor retention of micelles was also examined. FITC-albumin was used for comparison. The degree of extravasation from intact vessels in microtumors (rat sarcoma LY80) was extremely low and comparable to that from normal vessels. Cderiv pretreatment (1 or 3 days before administration of FITC-labeled compounds) markedly enhanced extravasation of such nanomicelles and albumin from vessels that survived treatment and had restored blood flow. A high concentration of extravasated macromolecules remained even 24 h later in tissue areas whose microcirculatory function had collapsed. Tumors receiving 10 Gy irradiation 3 days before the macromolecules evidenced gradual removal of extravasated macromolecules, which did not accumulate in those areas, despite extravasation from tumor vessels. Our results strongly suggest that pretreatment with Cderiv is quite effective for maintaining microtumor concentrations of nanomicelles and albumin associated with anticancer or diagnostic drugs.
|
10.1002/jps.22038
|
pubmed_675_7439
|
Zeolite has a high adsorption capacity for heavy metals, but it is difficult to separate from the medium because of its small particle size. In this study, magnetic zeolite was synthesized from natural, low-grade molybdenum ore by adding nano ferroferric oxide (saturation magnetization 83.43 emu/g) directly in the hydrothermal synthesis process, which was used to adsorb cadmium from wastewater. The results of scanning electron microscopy showed that the nano ferroferric oxide was adhered to the surface of the zeolite to make it magnetic. The vibrating sample magnetometer showed that the larger the amount of nano ferroferric oxide added, the higher the saturation magnetization of the magnetic zeolite. The saturation magnetization of the magnetic zeolite with a loading proportion of 25% was 18.18 emu/g with a specific surface area of 459.8 m2/g. The adsorption experiments showed that when the pH value is greater than 4, the adsorption capacity of magnetic zeolite is high and stable, and the theoretical maximum adsorption capacity is 204.2 mg Cd/g. Na+ and Ca2+ have different inhibitory functions on the adsorption capacity. The mapping graphs showed that cadmium is captured by the magnetic zeolite after contact with cadmium, and XRD confirmed the presence of cadmium oxide in the magnetic zeolite after adsorption, XPS and EDS results indicated that ion exchange is one of the main mechanisms of cadmium adsorption by magnetic zeolites, and electrostatic adsorption may also have a contribution.
|
10.1016/j.scitotenv.2021.145355
|
pubmed_199_5786
|
The role of accessory cells (AC) in the initiation of mitogen-induced T cell proliferation was examined by comparing the effect of intact macrophages (M phi) with that of 4-beta-phorbol 12-myristate 13-acetate (PMA). In high-density cultures, purified guinea pig T cells failed to proliferate in response to stimulation with phytohemagglutinin (PHA), concanavalin A (Con A), or PMA alone. The addition of M phi to PHA or Con A but not PMA-stimulated cultures restored T cell proliferation. The addition of PMA to high-density T cell cultures stimulated with PHA or Con A also permitted [3H]thymidine incorporation, but was less effective than intact M phi in this regard. This action of PMA was dependent on the small number of AC contaminating the T cell cultures as evidenced by the finding that PMA could not support mitogen responsiveness of T cells that had been depleted of Ia-bearing cells by planning, even when these cells were cultured at high density. When PMA was added to T cell cultures supported by optimal numbers of M phi, catalase-reversible suppression of responses was noted. Even in cultures containing catalase, PMA failed to enhance responsiveness above that supported by optimal numbers of M phi. A low-density culture system was used to examine in greater detail the possibility that PMA could completely substitute for M phi in promoting T cells activation. In low-density cultures, mitogen-induced T cell proliferation required intact M phi. PMA could not support responses even in cultures supplemented with interleukin 1-containing M phi supernatants or purified interleukin 2 alone or in combination. Similar results were found in high-density cultures of T cells depleted of Ia-bearing cells. These results support a model of T cell activation in which AC play at least two distinct roles. The initiation of the response requires a signal conveyed by an intact M phi, which cannot be provided by either a M phi supernatant factor or PMA. The response can be amplified by additional M phi or M phi supernatant factors. PMA can substitute for M phi in this regard and can provide the signal necessary for amplification of T cell proliferation supported by small numbers of intact AC.
|
pubmed_199_5786
|
pubmed_95_2457
|
1. The present study investigated whether a low nitrate/nitrite diet could minimize variability in the measurement of endogenous plasma and urine nitric oxide (NO) metabolites, nitrate and nitrite (NOx) in normal subjects. 2. Nitrate and nitrite concentrations were measured in plasma and urine as indicators of NO production in six subjects during a free diet and then during a low nitrate/nitrite diet for 6 days. 3. The plasma concentration and 24 h urine NOx/creatinine ratio were significantly lower on the low nitrate/nitrite diet than on the free diet (P < 0.01). Nitric oxide production appeared to vary greatly within and between subjects, but these variations were substantially decreased by the fourth day of a low nitrate/nitrite diet. 4. Human plasma and urine NOx measurements should be determined after a low nitrate/nitrite diet for at least 4 days.
|
10.1111/j.1440-1681.1997.tb01212.x
|
pubmed_397_17431
|
BACKGROUND
The Notch1-signaling pathway has been shown to regulate the differentiation and growth of carcinoid tumor cells. However, the molecules that mediate Notch1 signaling, as well as their potential roles in regulating the growth of carcinoid tumors, have not been characterized. We and others have shown previously that the transcription factor Hairy Enhancer of Split-1 (HES-1) is upregulated in response to Notch1 signaling, demonstrating that it is a Notch1 effector. We hypothesized that HES-1 may be the essential downstream factor in Notch1-mediated growth regulation of carcinoid tumors.
METHODS
H727 carcinoid tumor cells were transduced stably with a doxycycline-inducible HES-1 construct, creating H727-HES-1 cells. H727-TRE (vector-only control) and H727-HES-1 cells were then treated with varying concentrations of doxycycline to achieve increasing levels of HES-1 protein expression. Cell proliferation was determined with the use of a cell viability assay.
RESULTS
Treatment of H727-HES-1 cells with increasing dosages of doxycycline resulted in dose-dependent increases in HES-1 protein by Western blot analysis. Importantly, induction of HES-1 in carcinoid tumor cells led to suppression of tumor cellular proliferation. Moreover, the degree of carcinoid growth inhibition appeared to be proportional to the level of HES-1 induction.
CONCLUSIONS
HES-1 alone can regulate the growth of carcinoid tumor cells. Furthermore, these results suggest that HES-1 may be the critical downstream effector in the Notch1-signaling pathway.
|
10.1016/j.surg.2005.05.027
|
pubmed_830_19980
|
Aerobic metabolism is fundamental for almost all animal life. Cellular consumption of oxygen (O(2)) and production of carbon dioxide (CO(2)) signal metabolic states and physiological stresses. These respiratory gases are also detected as environmental cues that can signal external food quality and the presence of prey, predators and mates. In both contexts, animal nervous systems are endowed with mechanisms for sensing O(2)/CO(2) to trigger appropriate behaviors and maintain homeostasis of internal O(2)/CO(2). Although different animal species show different behavioral responses to O(2)/CO(2), some underlying molecular mechanisms and pathways that function in the detection of respiratory gases are fundamentally similar and evolutionarily conserved. Studies of Caenorhabditis elegans and Drosophila melanogaster have identified roles for cyclic nucleotide signaling and the hypoxia inducible factor (HIF) transcriptional pathway in mediating behavioral responses to respiratory gases. Understanding how simple invertebrate nervous systems detect respiratory gases to control behavior might reveal general principles common to nematodes, insects and vertebrates that function in the molecular sensing of respiratory gases and the neural control of animal behaviors.
|
10.1007/s11515-012-1219-x
|
pubmed_784_6393
|
An examination of 200 serum samples from unvaccinated indigenous (local) chickens in Maiduguri, Borno State (Nigeria) using the haemagglutination inhibition (HI) test showed 73 sera to be positive and 127 to be negative for antibodies against Newcastle disease virus. The highest antibody titre observed was 1:128. The prevalence rate was higher (46.9%) in adult chickens than in young chickens of less than 12 weeks (23%). Presence of HI antibodies in unvaccinated indigenous chickens indicates that these birds had contracted infection and recovered thereafter.
|
10.20506/rst.11.3.615
|
pubmed_329_13163
|
Mixed gliomas, primarily oligoastrocytomas, account for about 5%-10% of all gliomas. Distinguishing oligoastrocytoma based on histological features alone has limitations in predicting the exact biological behavior, necessitating ancillary markers for greater specificity. In this case report, human telomerase reverse transcriptase (hTERT) and high mobility group-A1 (HMGA1); markers of proliferation and stemness, have been quantitatively analyzed in formalin-fixed paraffin-embedded tissue samples of a 34 years old patient with oligoastrocytoma. Customized florescence-based immunohistochemistry protocol with enhanced sensitivity and specificity is used in the study. The patient presented with a history of generalized seizures and his magnetic resonance imaging scans revealed infiltrative ill-defined mass lesion with calcified foci within the left frontal white matter, suggestive of glioma. He was surgically treated at our center for four consecutive clinical events. Histopathologically, the tumor was identified as oligoastrocytoma-grade II followed by two recurrence events and final progression to grade III. Overall survival of the patient without adjuvant therapy was more than 9 years. Glial fibrillary acidic protein, p53, Ki-67, nuclear atypia index, pre-operative neutrophil-lymphocyte ratio, are the other parameters assessed. Findings suggest that hTERT and HMGA1 are linked to tumor recurrence and progression. Established markers can assist in defining precise histopathological grade in conjuction with conventional markers in clinical setup.
|
10.12998/wjcc.v4.i9.296
|
pubmed_71_3173
|
A label-free photoelectrochemical (PEC) aptasensor for K+ was first constructed by direct self-assembly of the K+ aptamer onto the electrodeposited Mn-doped ZnO nanorods. In the presence of K+, the conformation of G-quadruplex changes to a K+-stabilized conformation, which can efficiently prevent the quercetin electron donor from reaching the functionalized photoanode, thus proportionately affecting the quercetin-enhanced photocurrent response. Under the optimal experimental conditions, the fabricated biosensor exhibited a linear response in the K+ concentration range of 0.012 to 12.32 nmol L-1, with a detection limit of 4.0 pmol L-1, which was 3-5 orders of magnitude lower than that of most of the recently reported methods. The presence of other ions did not interfere with the detection of K+, and the results in serum samples agreed well with those obtained by ICP-MS. Using K+ as the detection model, this novel PEC aptasensor exhibited a good performance in terms of ultrasensitivity, selectivity and simplicity, and it was economical. As regards the electrode modification, this work provided a convenient direct self-assembly strategy that did not require the use of ionic polymers such as PDDA as a binder. Thus, this study paves the way for the immobilization of molecular probes for label-free PEC aptasensing.
|
10.1039/c7an00446j
|
pubmed_576_3674
|
Sympathetic neurocirculatory failure (SNF) features orthostatic hypotension and abnormal beat-to-beat blood pressure (BP) responses to the Valsalva maneuver. This article describes a new sign of SNF, based on changes in BP after premature ventricular contractions (PVCs). Records of supine beat-to-beat BP at rest were reviewed from 22 patients with SNF and 52 control subjects. Records were also taken during intravenous infusion of the ganglion blocker trimethaphan from 38 control subjects. In all 10 control subjects who had PVCs, after the postextrasystolic beat, mean arterial pressure increased progressively to levels higher than before the PVC, peaking at about the eighth beat. In contrast, in all 13 patients with SNF who had PVCs, after the postextrasystolic beat, BP decreased to less than baseline and then increased gradually back to baseline. In all 3 control subjects who had at least one PVC before trimethaphan infusion and another during trimethaphan infusion, the post-PVC pressure pattern during trimethaphan infusion resembled that in SNF patients. Because of a brief increase in sympathetic cardiovascular outflows, after a PVC, BP increases progressively to greater than pre-PVC values, mimicking the pressure overshoot after release of the Valsalva maneuver. Just as the absence of the overshoot of BP after release of the Valsalva maneuver supports a diagnosis of SNF, so does the absence of the overshoot after a PVC.
|
10.1007/BF02279893
|
pubmed_92_7123
|
Stereotypy is often characterized as repetitious, invariant behavior that generates its own reinforcing consequence. Stereotypy represents a unique treatment challenge, because the consequences produced by stereotypy cannot be directly controlled by the practitioner. Likewise, practitioners have relatively few options for identifying the function of repetitive behavior. Recently, several researchers have been conducting empirical studies to address these issues. This article introduces a special issue presenting some of these recent developments in the assessment and treatment of stereotypy and related behavior.
|
10.1177/0145445514540914
|
pubmed_741_6615
|
We treated a patient with avascular necrosis of the carpal scaphoid associated with progressive systemic sclerosis. Aetiology and histology of this unusual condition are discussed in relation to the underlying disease and the anatomical characteristics of the carpal scaphoid. Resection of the carpal scaphoid and replacement were successful.
|
pubmed_741_6615
|
pubmed_851_23978
|
Whooping cough, or pertussis, is a contagious disease of the respiratory tract that is re-emerging worldwide despite high vaccination coverage. The causative agent of this disease is the Gram-negative Bordetella pertussis. Knowledge on complement evasion strategies of this pathogen is limited. However, this is of great importance for future vaccine development as it has become apparent that a novel pertussis vaccine is needed. Here, we unravel the effect of Virulence associated gene 8 (Vag8) of B. pertussis on the human complement system at the molecular level. We show that both recombinant and endogenously secreted Vag8 inhibit complement deposition on the bacterial surface at the level of C4b. We reveal that Vag8 binding to human C1-inhibitor (C1-inh) interferes with the binding of C1-inh to C1s, C1r and MASP-2, resulting in the release of active proteases that subsequently cleave C2 and C4 away from the bacterial surface. We demonstrate that the depletion of these complement components in the bacterial surrounding and subsequent decreased deposition on B. pertussis leads to less complement-mediated bacterial killing. Vag8 is the first protein described that specifically prevents C1s, C1r and MASP-2 binding to C1-inh and thereby mediates complement consumption away from the bacterial surface. Unravelling the mechanism of this unique complement evasion strategy of B. pertussis is one of the first steps towards understanding the interactions between the first line of defense complement and B. pertussis.
|
10.1371/journal.ppat.1006531
|
pubmed_1025_13199
|
Timely registration of fatalities is important for the assessment of course, extent, risk of age groups, and magnitude or severity of health threats. Nevertheless, timely data of casualties are not available on the state or national level. The current paper describes the implementation and structure of a surveillance system for the timely registration of casualties in the state of Hesse (Germany) and the experience obtained during the pandemic 2009/10. The delay of the case-based registration appears tolerable and after 2 weeks more than 80% of all deaths for a given week are registered. In 2008, the forwarding of the electronically registered data from the registry offices (95% of all cases) to the state statistical office (HSL) had been accelerated from a monthly to a weekly base. The HSL provides--on a weekly basis--this case-based data in accordance with data protection rules to the Hesse State Health Office (HLPUG, "Hessischer Landesprüfungs- und Untersuchungsamt im Gesundheitswesen"). During the pandemic, the data allowed assessment of the excess mortality with a delay of 2 weeks. No significant excess mortality was apparent; however, a slight increase was observed in the age groups 15-34, 35-49, and 50-59. Correlation of time with the severity of the A/H1N1v epidemic was not very strong. Hence, the data did not indicate an excess significantly exceeding the number of death cases registered with the mandatory reporting system of 21 cases for Hesse.
|
10.1007/s00103-011-1298-x
|
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