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pubmed_779_17252
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The prognosis of advanced esophageal cancer (EC) remains poor, and few effective agents are available. For advanced EC patients, a combination of platinum and fluoropyrimidine is recognized as the standard first-line treatment. After first-line treatment, taxane or irinotecan has been used. Based on the KEYNOTE-181 and the ATTRACTION-3 trials, immune checkpoint inhibitors (ICIs) such as pembrolizumab and nivolumab appear to prolong survival, compared with cytotoxic agents, as second-line treatments for advanced EC patients. In addition, ICIs have different safety profiles than conventional cytotoxic agents. Herein, we discuss the differences in the safety profiles of cytotoxic agents and ICIs for the treatment of advanced EC patients after first-line chemotherapy.ICIs as a second-line treatment are tolerable in advanced EC patients. Although infrequent, ICIs can cause immune-related adverse events that are sometimes fatal. Therefore, regular monitoring of physical and laboratory examinations is needed during and after the administration of ICIs. As the major toxicities of taxane are neutropenia and neuropathy, while those of irinotecan are neutropenia and diarrhea, appropriate supportive care or dose modification may be needed for individual patients. ICI-containing treatments have been developed not only as second-line treatments, but also as first-line treatments or for use in perioperative settings; thus, particular attention with regard to immune-related toxicities is needed.
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10.1080/14740338.2021.1955100
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pubmed_609_7348
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We assessed the efficacy of recombinant human interleukin-1 receptor antagonist (rhIL-1ra) on brain injury and edema formation after permanent middle cerebral artery occlusion (MCAo) in the rat. Previous studies showed that low amounts of rhIL-1ra injected directly into the brain significantly decreased infarct size after MCAo or excitotoxic injury in rats. Peripheral administration of rhIL-1ra (100 mg/kg sc at 0, 4, 8, 12, and 18 h after MCAo) significantly inhibited infarct size, by 46% (P < 0.05), measured at 24h. This was greater than the effect of MK801 administered immediately after MCAo (4 mg/kg ip, 0 h) which did not significantly reduce infarct size. rhIL-1ra (100 mg/kg also significantly inhibited cerebral edema formation by 49% (p< 0.05 measured 24 h after MCAo, but did not reduce edema formation measured 2 h after MCAo, but did not reduce edema formation measured 2 h after MCAo. Inhibition of infarction by rhIL-1ra was dependent on dose and time of administration. Together the results demonstrate that peripherally administered rhIL-1ra at high doses is able to mimic the efficacy of low dose of rhIL-1ra administered directly into the brain in a rodent model of stroke and that protection observed with rhIL-1ra was better than that offered by MK801 in this model.
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10.1006/exnr.1996.0059
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pubmed_1050_8161
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Aim of the study was to evaluate the influence of the EEG channels number on the brain networks' analysis, to establish whether and how much higher density EEG actually contributes to add supplementary information to brain networks analyses. 59 electrodes EEGs were recorded in 20 healthy subjects in eyes open and closed condition. For each condition, we analyzed the recording dataset of 59 channels, and three sub-datasets obtained by the selection of 44, 30, 19 channels from the 59 ones. Then we computed the EEG sources of current density and evaluated the SW index in the four EEGs data montages. Results showed that in the eyes open condition the number of recording channels influences more the SW index modulation respect that in the eyes closed condition. Conversely, in the eyes closed condition the brain activity is less affected by specific brain regions' activations and the signal's generators produced not significant variations on EEG data and consequently the small world network measure is not affected by the recording channels number. We can conclude that in the eyes closed condition, the 19 EEG channels is an acceptable montage to study brain networks' modulations, to both detect the higher and the lower brain waves' frequencies.
|
10.1016/j.brainresbull.2020.11.014
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pubmed_305_25135
|
Angle-closure glaucoma includes a number of entities with closed angle, elevated intraocular pressure, in association with optic nerve damage and visual field defects as common markers. These entities are characterized by irido-trabecular apposition, irido-trabecular synechiae or both. The angle configuration must be systematically checked at least one time in patients presenting with raised intraocular pressure or glaucoma. Gonioscopy represented for a long time the gold standard for clinically assessing anterior chamber angle structures and their configuration. However, the interpretation of gonio-scopic findings is subjective and only semiquantitative. With the development of new imaging techniques of the anterior segment, new analysis methods have also emerged. Ultrabiomicroscopy was the first method of analyzing the anterior segment and is still the only imaging technique for all anterior segment structures (especially the ciliary body). Another method is optical coherence tomography, a non-contact technique by which angle configuration can be assessed in a more rapid and less invasive manner. Recently developed Pentacam technology could represent in the near future a more quantitative, rapid and non-invasive screening tool which could allow early detection of angle closure glaucoma and narrow angle configurations by measuring a set of anterior chamber parameters. List of abbreviations: ACG -angle closure glaucoma, ASOCT-anterior segment optical coherence tomography UMB- ultrasound biomicroscopy (ultrabiomicroscopy), PAS-posterior angle synechiae ACD-anterior chamber depth, ACV-anterior chamber volume, PLI-periphery laser iridotomy.
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pubmed_305_25135
|
pubmed_748_18485
|
Some new oleanolic acid derivatives with lactame and thiolactame structures in the A- or C-ring were prepared and tested as percutaneous transport promoters in vitro. Their activity was comparable with activity of N-dodecylcaprolactame (Azone). A-Thiolactame derivative of methyl oleanolate (13) was the most effective compound.
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10.1016/j.bmcl.2004.06.087
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pubmed_372_12220
|
A 25-year-old woman with a background history of bronchial asthma and intellectual disability presented to hospital with progressively worsening dyspnoea. Despite testing negative four times for coronavirus disease infection by nasopharyngeal swab reverse-transcriptase polymerase chain reaction, her clinical symptoms of hypoxaemic respiratory failure and radiological findings on computed tomography pulmonary angiogram were consistent with coronavirus disease pneumonia. Although she made a quick recovery in the intensive care unit with a combination of empirical antibiotics, corticosteroids, high flow nasal oxygen, therapeutic anticoagulation and awake semi proning, her protracted hospital course due to persistent sinus tachycardia remained challenging. A diagnosis of potential postural orthostatic tachycardia syndrome was explored during the acute phase of illness following an active stand test and exclusion of other causes. She was treated with beta blockers as she failed to improve with non-pharmacological measures. We searched for similar cases by analysing the literature databases. Our case aims to stress the importance of recognising and treating patients with negative nasal reverse-transcriptase polymerase chain reaction swabs as coronavirus disease infection, especially if there is strong evidence of clinical and radiological findings where diagnosis is often under recognised in asthmatics with intellectual disability.
|
10.1177/2050313X211066647
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pubmed_49_11337
|
A double-blind study was performed in 305 patients to compare ketotifen capsule and clemastine tablet. Ketotifen alleviated eruption and itching to a significantly greater extent than clemastine. The utility rating of ketotifen was significantly higher than that of clemastine.
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pubmed_49_11337
|
pubmed_676_965
|
This paper analyzes the powerful professional and social forces arrayed against community control. True community control is seen to be in danger of being compromised and co-opted by the mental health establishment. A radical and untried proposition, the implementation of community control, awaits broader institutional and political reform.
|
10.1002/1520-6629(197801)6:1<3::aid-jcop2290060102>3.0.co;2-9
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pubmed_23_7802
|
Apoptosis has been described as an energy-consuming process. This combined in vivo/in vitro study investigated the effects of the antineoplastic agent gemcitabine on tumour metabolism and on the induction of apoptosis. Dynamic positron emission tomography (PET) measurements of fluorine-18 fluorodeoxyglucose (FDG) uptake were done in rats bearing Morris hepatoma prior to and after therapy with 90 mg gemcitabine/kg b.w. Furthermore, thymidine (TdR) incorporation into the DNA of these tumours was determined. In vitro measurements of FDG and TdR uptake were performed immediately and 24 h after the end of gemcitabine treatment, and the amount of apoptotic cells was determined using the TUNEL reaction. In vivo an increase in FDG transport and phosphorylation occurred early after gemcitabine treatment, although TdR incorporation into the DNA of the tumours declined. In vitro, an enhanced glucose transport, an increase in TdR uptake in the cytoplasm and a decrease in TdR incorporation in the nucleic acid fraction early after treatment occurred. Inhibition of glucose transport caused an increase in the amount of apoptotic cells. The increase in glucose uptake and TdR metabolism early after therapy is interpreted as a stress reaction of the tumour cells, protecting the cells from apoptosis during this early period after exposure to cytotoxic drugs like gemcitabine.
|
10.1007/s002590100489
|
pubmed_1122_18862
|
OBJECTIVE
A double-blind, multicenter, randomized trial was conducted to compare the side effects and efficacy of domperidone and metoclopramide in symptomatic diabetic gastroparesis.
METHODS
Ninety-three insulin-dependent diabetes patients with a > or = 3-month history of gastroparesis symptoms were recruited; 48 received domperidone 2 x 10-mg tablets 4 times daily, and 45 received metoclopramide 1 x 10-mg tablet + 1 placebo tablet 4 times daily. Nausea, vomiting, bloating/distension, and early satiety were evaluated for severity after 2 and 4 wk. Adverse central nervous system (CNS) effects of somnolence, akathisia, asthenia, anxiety, depression, and reduced mental acuity were elicited and graded for severity at 2 and 4 wk.
RESULTS
Domperidone and metoclopramide were equally effective in alleviating symptoms of diabetic gastroparesis. Elicited adverse CNS effects were more severe and more common with metoclopramide. Somnolence was acknowledged by 49% of patients (mean severity score, 1.03) after 4 wk of metoclopramide compared with 29% of patients (mean severity score, 0.49) after 4 wk of domperidone (incidence, p = 0.02; severity; p = 0.03). A reduction in mental acuity was acknowledged by 33% of patients (mean severity score, 0.62) after 4 wk of metoclopramide, compared with 20% of patients (mean severity score, 0.27) after 4 wk of domperidone (incidence, p = 0.04; severity, p = 0.04). Akathisia, asthenia, anxiety, and depression were also acknowledged less often, and at a lower severity, after 4 wk of domperidone, although these differences were not statistically significant.
CONCLUSIONS
Domperidone and metoclopramide effectively reduce the symptoms of diabetic gastroparesis; CNS side effects are more pronounced with metoclopramide.
|
10.1111/j.1572-0241.1999.00456.x
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pubmed_490_5044
|
BACKGROUND
The aim of this review was to estimate the lethal and exposure doses of a representative symptom (blindness) of methanol exposure in humans by reviewing data from previous articles.
METHODS
Available articles published from 1970 to 2016 that investigated the dose-response relationship for methanol exposure (i.e., the exposure concentration and the biological markers/clinical symptoms) were evaluated; the MEDLINE and RISS (Korean search engine) databases were searched. The available data from these articles were carefully selected to estimate the range and median of a lethal human dose. The regression equation and correlation coefficient (between the exposure level and urinary methanol concentration as a biological exposure marker) were assumed from the previous data.
RESULTS
The lethal human dose of pure methanol was estimated at 15.8-474 g/person as a range and as 56.2 g/person as the median. The dose-response relationship between methanol vapor in ambient air and urinary methanol concentrations was thought to be correlated. An oral intake of 3.16-11.85 g/person of pure methanol could cause blindness. The lethal dose from respiratory intake was reported to be 4000-13,000 mg/l. The initial concentration of optic neuritis and blindness were shown to be 228.5 and 1103 mg/l, respectively, for a 12-h exposure.
CONCLUSION
The concentration of biological exposure indices and clinical symptoms for methanol exposure might have a dose-response relationship according to previous articles. Even a low dose of pure methanol through oral or respiratory exposure might be lethal or result in blindness as a clinical symptom.
|
10.1186/s40557-017-0197-5
|
pubmed_1041_2083
|
Nephropathic cystinosis is a rare autosomal recessive disease characterised by raised intracellular levels of the amino acid, cystine. If untreated, the disease, progressively deteriorates towards end stage renal disease (ESRD) at the end of the first decade. The disease is caused by a defect in the lysosomal transport mechanism for cystine. The treatment of choice is the aminothiol cysteamine which acts as a lysine mimic. However, cysteamine possesses an offensive taste and smell and irritates the gastrointestinal tract leading to nausea and vomiting following administration. Furthermore, the rapid metabolism of cysteamine requires oral administration every 6 h for life, in consequence, the patient compliance is poor. As part of our continuing work to obtain new pro-drugs for the treatment of this genetic disease, we have synthesised a folate derivative of cystamine, the disulfide derivative of cysteamine. This new pro-drug was non cytotoxic, showed greater ability to deplete intralysosomal cystine than the current treatment, and, in fact has been the most effective reducer of intralysosomal cystine discovered in our laboratories to date.
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10.1016/j.bmcl.2011.02.048
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pubmed_392_19717
|
Treatment of articular cartilage injuries especially osteochondral tissue requires intervention of bioengineered scaffold. In this study, we investigated the potential of the tissue-engineered cryogel scaffold fabricated using cryogelation technology. Two types of cryogels viz. chitosan-gelatin-chondroitin sulfate (CGC) for articular cartilage and nano-hydroxyapatite-gelatin (HG) for subchondral bone were fabricated. Further, novel bilayer cryogel designed using single process fabrication of two layers (CGC as top layer and HG as the lower layer) was designed to mimic osteochondral unit. CGC cryogel was tested for their biocompatibility using the enzymatically isolated chondrcoytes from goat articular cartilage while HG cryogel was tested using pre-osteoblast cell line. Extracellular vesicles, specifically exosomes were isolated from the spent media of chondrocytes to validate their effect over cell proliferation and migration which are required for defect healing and infiltration respectively. These isolated exosomes were characterized and analyzed for confirming their size distribution profile and visualized morphologically using advanced microscopy techniques. For cartilage part, CGC cryogels were examined as delivery system for delivering exosomes at defect site, where 80% of release was observed in 72 h. Release of 18.7 µg chondroitin sulfate/mg cryogel was obtained in a period of one week from CGC cryogel (termed cryogel extract) which has chondroprotective effect. Further, effect of exosome concentration (10 and 20 µg/ml), CGC extract and combination of exosome and CGC extract (Exo-Ex) were assessed over the chondrocytes. In addition, in vitro scratch wound assay was performed to analyse the migration capacity over the micro-injury when treated with exosomes, cryogel extract and Exo-Ex. The overall results thus answer key questions of therapeutic potential of chondrocyte exosomes, cryogel extract in addition to potential of CGC and HG cryogel for osteochondral repair.
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10.1002/bit.27982
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pubmed_648_274
|
Both degenerative cervical myelopathy (DCM) and anemia are common among older patients, however insufficient data exists evaluating their co-occurrence and the influence of anemia on baseline neurological status. To address this, we examined a retrospective multicenter series of patients treated for DCM or radiculopathy. Myelopathy was graded using the Nurick scale. Established criteria for diagnosing abnormalities were used to identify blood abnormalities, including macrocytic and microcytic anemia. Multivariable regression was used to determine the impact of hematological anomalies on Nurick grades. In our analysis, we included 725 patients (age of 57.1 ± 11.7), of whom 398 presented with myelopathy and 327 presented with radiculopathy alone. Twenty six percent of all patients were anemic at baseline and the mean preoperative Nurick grade across all patients was 2.09 ± 1.29; mean Nurick grade amongst those with DCM was 2.98 ± 1.12. Compared to those with myelopathy, patients with radiculopathy were significantly younger (53.8 ± 11.0 vs 59.8 ± 11.6, p < 0.001) and less likely to be anemic (16.8% vs 33.7%, p < 0.0001). Nurick grading was significantly higher in myelopathy patients with anemia (3.13 ± 1.19 vs 2.91 ± 1.07, p = 0.05) and macrocytic anemia (4.00 ± 1.41 vs 2.97 ± 1.11, p = 0.04). Multivariate regression demonstrated that anemia (p < 0.001), age (p < 0.0001), and posterior surgical approach (p < 0.0001) were related to worse preoperative Nurick grade. In sum, these data suggest that anemia and degenerative cervical spine pathologies commonly co-occur. Anemia, and macrocytic anemia specifically, is associated with poorer neurological status in myelopathic patients. These data suggest anemia may influence baseline neurological status and impact surgical recovery in patients treated for DCM or radiculopathy.
|
10.1016/j.jocn.2019.11.027
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pubmed_602_16692
|
There has been increasing interest in a potential role for fatty acids in adversely affecting organismal substrate utilization and contributing to the cardiovascular complications in insulin resistance. Fatty acids have already been implicated in regulating the expression of a number of genes in resident cells of the vessel wall. In the current studies, we evaluated a potential role for fatty acids in the regulation of macrophage apoE expression. Incubation in oleic acid increased the synthesis and secretion of apoE by human monocyte-derived macrophages. Part of this stimulation was mediated at a post-translational locus. Oleic acid increased the secretion of apoE from macrophages that constitutively expressed a human apoE3 cDNA. Incubation in palmitic acid decreased apoE secretion from these cells. The effect of oleic acid on apoE secretion could not be accounted for by the known effect of fatty acid on cellular sterol, because incubation in oleic acid did not suppress the degradation of nascent apoE. Incubation in oleic acid for at least 6 h was required to observe an effect on apoE secretion. Oleic acid altered the glycosylation pattern of cellular and secreted apoE, with a loss of the most heavily sialylated isoform. Oleic acid had no effect on the glycosylation of interleukin 6 secreted from macrophages. Elimination of apoE glycosylation, by substitution of threonine 194 with alanine, eliminated oleic acid-mediated stimulation of apoE secretion. These results indicate that oleic acid increases apoE secretion from macrophages at a locus involving post-translational glycosylation.
|
10.1074/jbc.M402631200
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pubmed_517_24338
|
OBJECTIVE
The goal of this study was to develop an in-depth understanding of how a health information exchange (HIE) fits into clinical workflow at multiple clinical sites.
MATERIALS AND METHODS
The ethnographic qualitative study was conducted over a 9-month period in six emergency departments (ED) and eight ambulatory clinics in Memphis, Tennessee, USA. Data were collected using direct observation, informal interviews during observation, and formal semi-structured interviews. The authors observed for over 180 h, during which providers used the exchange 130 times.
RESULTS
HIE-related workflow was modeled for each ED site and ambulatory clinic group and substantial site-to-site workflow differences were identified. Common patterns in HIE-related workflow were also identified across all sites, leading to the development of two role-based workflow models: nurse based and physician based. The workflow elements framework was applied to the two role-based patterns. An in-depth description was developed of how providers integrated HIE into existing clinical workflow, including prompts for HIE use.
DISCUSSION
Workflow differed substantially among sites, but two general role-based HIE usage models were identified. Although providers used HIE to improve continuity of patient care, patient-provider trust played a significant role. Types of information retrieved related to roles, with nurses seeking to retrieve recent hospitalization data and more open-ended usage by nurse practitioners and physicians. User and role-specific customization to accommodate differences in workflow and information needs may increase the adoption and use of HIE.
CONCLUSION
Understanding end users' perspectives towards HIE technology is crucial to the long-term success of HIE. By applying qualitative methods, an in-depth understanding of HIE usage was developed.
|
10.1136/amiajnl-2011-000432
|
pubmed_463_10110
|
METHODS
We searched MEDLINE and EMBASE for epidemiologic studies on occupational exposure to methylene chloride and risk of cancer. Estimates of study-specific odds ratios (ORs) were calculated using inverse-variance-weighted fixed-effects models and random-effects models. Statistical tests for heterogeneity were applied.
RESULTS
We summarized data from five cohort studies and 13 case-control studies. The pooled OR for multiple myeloma was (OR 2.04; 95 % CI 1.31-3.17) in relation to occupational exposure to methylene chloride but not for non-Hodgkin's lymphoma, leukemia, breast, bronchus, trachea and lung, brain and other CNS, biliary passages and liver, prostate, pancreas, and rectum. Furthermore, we focused on specific outcomes for non-Hodgkin's lymphoma and multiple myeloma because of exposure misclassification. The pooling OR for non-Hodgkin's lymphoma and multiple myeloma was 1.42 (95 % CI 1.10-1.83) with moderate degree of heterogeneity among the studies (I (2) = 26.9 %, p = 0.205).
CONCLUSIONS
We found an excess risk of multiple myeloma. The non-Hodgkin's lymphoma and leukemia that have shown weak effects should be investigated further.
|
10.1007/s10552-013-0283-0
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pubmed_1027_13201
|
We report a 25-year-old male with fever, generalized lymphadenopathy and an erythematosus maculo-papular eruption affecting face and upper body. A diagnosis of Kikuchi disease (necrotizing histiocytic lymphadenitis) was made on lymph node histology. The patient was found to be positive for the human T-cell leukaemia lymphoma virus (HTLV1). Kikuchi disease has been reported in association with infections such as Epstein-Barr virus (EBV), herpes (HHV6) and toxoplasmosis, but to our knowledge this is the first case of Kikuchi disease associated with HTLV1.
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pubmed_1027_13201
|
pubmed_134_23691
|
We examined the modulation of adrenergic cell signaling by the human mineralocorticoid receptor (hMR) in renal cell lines (RC.SV3) stably transfected with full-length (M cells) or truncated hMR. Isoproterenol time-dependently increased intracellular cAMP formation, which was up to six-fold higher in M cells than in parental RC.SV3 cells. Incubation of cells with aldosterone or spironolactone for 24h neither changed the basal nor the isoproterenol-stimulated cAMP level in both cell lines, while inhibitor studies revealed that those effects are mediated by the beta(2)-adrenergic receptor. Expression of stimulatory G protein alpha was increased and that of G protein receptor coupled kinase 3 (GRK3) was reduced by hMR. Deletion studies of cells stably transfected with truncated hMR indicated that the N-terminal and the DNA binding domains of hMR are essential for enhancement of the catecholamine signal transduction pathway. In conclusion, our findings suggest a novel interplay between cAMP and MR signaling pathways.
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10.1016/j.mce.2004.12.004
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pubmed_710_353
|
Runx1 is an important haematopoietic transcription factor as stressed by its involvement in a number of haematological malignancies. Furthermore, it is a key regulator of the emergence of the first haematopoietic stem cells (HSCs) during development. The transcription factor Gata3 has also been linked to haematological disease and was shown to promote HSC production in the embryo by inducing the secretion of important niche factors. Both proteins are expressed in several different cell types within the aorta-gonads-mesonephros (AGM) region, in which the first HSCs are generated; however, a direct interaction between these two key transcription factors in the context of embryonic HSC production has not formally been demonstrated. In this current study, we have detected co-localisation of Runx1 and Gata3 in rare sub-aortic mesenchymal cells in the AGM. Furthermore, the expression of Runx1 is reduced in Gata3 -/- embryos, which also display a shift in HSC emergence. Using an AGM-derived cell line as a model for the stromal microenvironment in the AGM and performing ChIP-Seq and ChIP-on-chip experiments, we demonstrate that Runx1, together with other key niche factors, is a direct target gene of Gata3. In addition, we can pinpoint Gata3 binding to the Runx1 locus at specific enhancer elements which are active in the microenvironment. These results reveal a direct interaction between Gata3 and Runx1 in the niche that supports embryonic HSCs and highlight a dual role for Runx1 in driving the transdifferentiation of haemogenic endothelial cells into HSCs as well as in the stromal cells that support this process.
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10.1002/iub.2184
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pubmed_534_16634
|
Marine organisms have the ability of producing enzymes with unique properties compared to those of the same enzymes from terrestrial organisms. α-Amylases are among the most important extracellular enzymes found in various groups of organisms such as plants, animals and microorganisms. They play important roles in their carbohydrates metabolism of each organism. Microbial production of α-amylases is more effective than other sources of the enzyme. Many microorganisms are known to produce α-amylase including bacteria, yeasts, fungi and actinomycetes. However, enzymes from fungal and bacterial sources have dominated applications in industrial sectors. This review deals with what is known about the kinetics, biochemical properties and applications of these enzymes that have only been found in them and not in other α-amylases, and discussing their mechanistic and regulatory implications.
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pubmed_534_16634
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pubmed_369_21942
|
BACKGROUND
The millennial learner is reliant on technology to gain knowledge. Social media in the form of Twitter and Facebook provide a unique way to reach these learners.
AIMS
To demonstrate a supplement to a curriculum using "push technology" via Twitter and Facebook to deliver educational content to mobile devices.
METHODS
A curriculum consisting of high-yield ultrasound concepts was developed and posted to Twitter @EDUltrasound daily. Followers received tweets "pushed" directly to their mobile devices. Following the year-long program, followers were surveyed regarding the program's effectiveness. To determine the ways in which tweets were reaching users, followers were categorized demographically.
RESULTS
Daily "tweets" were posted each morning beginning on July 1, 2010. By the end of the year, there were 87 followers on Twitter and 78 on Facebook. The majority of followers (55.6%) had not previously used Twitter. The majority of followers (88.9%) found Twitter user-friendly, while most (81.5%) found the information useful.
CONCLUSIONS
Due to ease of use and widespread applicability, Twitter and Facebook are excellent applications of "push technology" as a means to deliver educational content. This pilot project demonstrates the potential of social media to both supplement and enhance traditional educational methods.
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10.3109/0142159X.2012.668245
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pubmed_186_20892
|
Oxidative damage to the constituents of the eye lens is a major mechanism in the initiation and development of cataract. Lunasin, a 43-amino acids chemoprevention peptide, has been proved to possess potent anti-oxidative activity other than its established anticancer activities. Herein, we explored whether lunasin has preventative effects on d-galactose-induced experimental cataract in rat. After modeling, SD rats were administrated by instillation, 80 µM of lunasin eye drops to each eye thrice daily and consecutively for 30 days. As a result, lunasin treatment effectively inhibited the progression of d-galactose-induced experimental cataract, and protected the lenses of rats from oxidative damage and attenuated the lipid peroxidation through up-regulation of antioxidant enzymes, and inhibited the activation of polyol pathway by decreasing AR activity. Additionally, in vitro studies proved that lunasin treatment could protect human lens epithelial cells (hLECs) against d-galactose induced cell damage and apoptosis, and up-regulate antioxidant enzymes. This is the first demonstration that lunasin could inhibit d-galactose-induced experimental cataract in rats by protecting against oxidative damage and inhibiting the activation of polyol pathway.
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10.2174/0929866523666160505121047
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pubmed_290_22985
|
BACKGROUND
Stress signals during sucking activity such as nasal flaring, head turning, and extraneous movements of the body have been attributed to incoordination of sucking, swallowing, and respiration (SSR) in premature infants. However, the association of uncoordinated sucking pattern with developmental outcomes has not yet been investigated. The aim of this study was to investigate whether uncoordinated sucking pattern during bottle-feeding in premature infants is associated with the developmental outcomes at 8-12 and 18-24 months of age (corrected for prematurity).
METHODS
We retrospectively reviewed the medical records and video recordings for the Neonatal Oral-Motor Assessment Scale (NOMAS) of premature infants and divided them into two groups based on the presence or absence of incoordination. The Bayley-III cognition composite scores of the incoordination-positive and incoordination-negative group were compared at 8-12 and 18-24 months of age.
RESULTS
Seventy premature infants exhibited a disorganized sucking pattern according to the NOMAS. The average Bayley-III cognition composite scores at 8-12 months of age were 92.5 ± 15.6 and 103.0 ± 11.3 for the incoordination-positive (n = 22) and incoordination-negative groups (n = 48), respectively (p = 0.002). The average Bayley-III cognition composite scores at 18-24 months were 90.0 ± 17.9 and 100.7 ± 11.5 for the incoordination-positive (n = 21) and incoordination-negative groups (n = 46), respectively (p = 0.005). A multiple linear regression analysis indicated that the presence of uncoordinated sucking pattern, grade 3 or 4 germinal matrix hemorrhage-intraventricular hemorrhage, and moderate to severe bronchopulmonary dysplasia were independently associated with cognitive development at 18-24 months of age.
CONCLUSIONS
Uncoordinated sucking pattern in premature infants was independently associated with a higher risk of abnormal developmental outcome in the cognitive domain of the Bayley-III at both 8-12 and 18-24 months. There may be a need for periodic follow-up and early intervention for developmental delay when incoordination of SSR that results in stress signals on the NOMAS is observed before 40 weeks postmenstrual age.
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10.1186/s12887-019-1811-1
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pubmed_738_5825
|
Two o-benzoquinone derivatives of isoindoline were synthesized for use as building blocks to incorporate isoindoline nitroxides into different compounds and materials. These o-quinones were condensed with a number of o-phenylenediamines to form isoindoline-phenazines in high yields. Subsequent oxidation gave phenazine-di-N-oxide isoindoline nitroxides that were evaluated for noncovalent and site-directed spin-labeling of duplex DNA and RNA that contained abasic sites. Although only minor binding was observed for RNA, the unsubstituted phenazine-N,N-dioxide tetramethyl isoindoline nitroxide showed high binding affinity and selectivity towards abasic sites in duplex DNA that contained cytosine as the orphan base.
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10.1002/cbic.202000128
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pubmed_931_7675
|
Four species of the Hawaiian Drosophila planitibia subgroup which are homosequential in their polytene chromosomes are resident on the islands of Molokai, Maui and Hawaii. Comparisons of DNA sequence divergence in these four have been made by hybridization of total single-copy radiolabeled tracer DNA from each of the species with excess nonlabeled DNA from each of the species, and measurement of the reduction of average melting temperature (DeltaTma) was made in 2.4 m tetraethyl ammonium chloride. The mean DeltaTma between either D. heteroneura or D. silvestris and either D. planitibia or D. differens was found to be 1.06 degrees , whereas the difference between D. planitibia and D. differens in 0.65 degrees and between D. heteroneura and D. silvestris is 0.75 degrees . These measurements taken together with the distances calculated from isozyme studies, chromosomal relationships, as well as the island locations indicate that the ancestor of these species diverged from other planitibia subgroup flies on Molokai [age 1.8 million years before present, (My BP)]. We hypothesize that one line became the present-day D. differens and diverged probably at the time of formation of East Maui (0.8-1 My BP) to form the species D. planitibia. Flies from the other line migrated to Hawaii soon after its formation (0.7 My BP) to form the two species D. heteroneura and D. silvestris.
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10.1093/genetics/104.2.353
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pubmed_261_16688
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The article provides data on the use of a two-level epidural analgesia as a component of general anesthesia and postoperative analgesia in surgical treatment of scoliosis on the front and back structures of the spine. The study included 150 patients aged from 12 to 25 years. All the patients were divided into 4 groups. The patients of the 2-nd and 3-rd groups before the main stage was carried out an epidural analgesia with 0.75% ropivacaine and sevorane-propofol general anaesthesia . In the 1-st and 4-th group carried out an propofol-fentanyl TIVA or inhalational sevorane-fentanyl one. The best result were obtained in the 3-rd group, where they carried out the infusion 0.2% ropivacaine with fentanyl (1 microg/ml) and epinephrine (2 microg/ml) via 2 epidural catheters. It was noted decreased blood loss by more than 50% in groups with epidural analgesia.
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pubmed_261_16688
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pubmed_200_8888
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A bipolar mitotic spindle facilitates the equal segregation of chromosomes to two daughter cells. To achieve bipolar attachment of microtubules to kinetochores of sister chromatids, chromatids must remain paired after replication. This cohesion is mediated by the conserved cohesin complex comprised of SMC1, SMC3, SCC1, and either SA1 or SA2 in humans. Because defects in spindle assembly or sister chromatid cohesion can lead to aneuploidy in daughter cells, proper regulation of these processes is essential for fidelity in chromosome segregation. In an RNAi screen for regulators of spindle assembly, we identify the deubiquitinase USP37 as a regulator of mitotic progression, centrosome integrity, and chromosome alignment. USP37 associates with cohesin and contributes to sister chromatid resolution. Cohesion defects are rescued by expression of an RNAi-resistant USP37, but not the catalytically impaired USP37(C350A) mutant. Further, USP37 associates with WAPL, a negative regulator of cohesion necessary for cohesin release in prophase, in a manner dependent on USP37's second and third ubiquitin-interacting motifs. Depletion of USP37 reduces the stability of chromatin-associated WAPL and increases the fraction of WAPL that is more heavily ubiquitylated in mitosis. Consistently, overexpression of USP37(C350A) results in increased modification of WAPL, and addition of purified USP37(WT), but not USP37(C350A), to WAPL immunoprecipitates results in a reduction of ubiquitylated products. Taken together, our results ascribe a novel function for USP37 in mitotic progression and further suggest that USP37 positively regulates the stability of chromatin-associated WAPL to facilitate sister chromatid resolution.
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pubmed_200_8888
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pubmed_615_17074
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BACKGROUND
Schistosomiasis mansoni is an endemic parasitic disease and a public health problem in Northeast Brazil. In some patients, hepatic abnormalities lead to periportal fibrosis and result in the most severe clinical form, hepatosplenic schistosomiasis. This study aimed to evaluate whether abnormal blood coagulation and liver function tests in patients with hepatosplenic schistosomiasis (n = 55) correlate with the severity of their periportal fibrosis.
METHODOLOGY/PRINCIPAL FINDINGS
Blood samples were used for liver function tests, hemogram and prothrombin time (International Normalized Ratio, INR). The blood coagulation factors (II, VII, VIII, IX and X), protein C and antithrombin IIa (ATIIa), plasminogen activator inhibitor 1 (PAI-1) and D-dimer were measured by photometry or enzyme linked immunosorbent assay. Hyperfibrinolysis was defined on the basis of PAI-1 levels and a D-dimer concentration greater than a standard cut-off of 483 ng/mL. Standard liver function tests were all abnormal in the patient group compared to healthy controls (n = 29), including raised serum transaminases (p<0.001) and lower levels of albumin (p = 0.0156). Platelet counts were 50% lower in patients, while for coagulation factors there was a 40% increase in the INR (p<0.001) and reduced levels of Factor VII and protein C in patients compared to the controls (both p<0.001). Additionally, patients with more advanced fibrosis (n = 38) had lower levels of protein C compared to those with only central fibrosis (p = 0.0124). The concentration of plasma PAI-1 in patients was one-third that of the control group (p<0.001), and D-dimer levels 2.2 times higher (p<0.001) with 13 of the 55 patients having levels above the cut-off.
CONCLUSION/SIGNIFICANCE
This study confirms that hemostatic abnormalities are associated with reduced liver function and increased liver fibrosis. Of note was the finding that a quarter of patients with hepatosplenic schistosomiasis and advanced periportal fibrosis have hyperfibrinolysis, as judged by excessive levels of D-dimer, which may predispose them to gastrointestinal bleeding.
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10.1371/journal.pntd.0002314
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pubmed_244_13397
|
BACKGROUND
Relamorelin, a pentapeptide ghrelin receptor agonist, accelerated gastric emptying significantly and improved symptoms in adults with diabetic gastroparesis in phase 2 trials.
AIM
To assess the safety and tolerability of relamorelin across phase 2 trials.
METHODS
Safety assessments in patients aged 18-75 years (weight, adverse events [AEs] and laboratory tests) from two randomised, double-blind phase 2 trials (NCT01571297, NCT02357420; results published previously) were reviewed descriptively. Analysis of covariance assessed treatment effect on glycated haemoglobin (HbA1c) and blood glucose post hoc. Phase 2a and 2b trial durations were, respectively, 4 weeks (relamorelin 10 µg once or twice daily [b.d.] or placebo b.d.) and 12 weeks (relamorelin 10, 30 or 100 µg or placebo b.d.) with 1- and 2-week, single-blind placebo run-ins.
RESULTS
Among 204 phase 2a and 393 phase 2b patients, respectively, 67% and 62% were female, and 88% and 89% had type 2 diabetes. Proportions of patients reporting serious AEs were similar across treatment groups, as were those with ≥1 treatment-emergent AE (TEAE). TEAE-related discontinuations were proportionally higher in relamorelin groups than placebo. Of 12 serious TEAEs in phase 2a, none occurred in >1 patient. In phase 2b, five serious TEAEs were reported in >1 patient, and one (100 µg) died (urosepsis), all unrelated to relamorelin. In phase 2b, increased HbA1c and fasting blood glucose levels were dose-related (P < 0.0001 and P = 0.0043, respectively).
CONCLUSIONS
Relamorelin showed acceptable safety and tolerability in phase 2 trials. Relamorelin may elevate blood glucose: this should be managed proactively in relamorelin-treated patients.
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10.1111/apt.15711
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pubmed_87_4742
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In this study, a layer-by-layer (LbL) assembly (HEP/CHI)5 microcapsule with doxorubicin hydrochloride (DOX) encapsulating inside was fabricated via alternatively depositing heparin (HEP) and chitosan (CHI) onto DOX-loaded CaCO3 templates. The microcapsules were of stable architecture and had good dispersity in aqueous medium. Fluorescence observation showed that DOX distributed both in the wall and in the cavity of microcapsules, while HEP presented in the capsule wall. The release rate of DOX increased at acidic pH as compared with that at basic pH, suggesting a pH-responsive drug release behavior. The microcapsules with positively charged CHI lying on the outer layer could protect HEP from heparanase degradation and achieve intracellular co-delivery of both DOX and HEP. Thus, the DOX-loaded microcapsules could have improved inhibition activity against A549 cells by combining pharmacological actions of DOX and HEP.
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pubmed_87_4742
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pubmed_249_14845
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Plexins comprise a family of transmembrane proteins (the plexin family) which are expressed in nervous tissues. Some plexins have been shown to interact directly with secreted or transmembrane semaphorins, while plexins belonging to the A subfamily are suggested to make complexes with other membrane proteins, neuropilins, and propagate chemorepulsive signals of secreted semaphorins of class 3 into cells or neurons. Despite that much information has been gathered on the plexin-semaphorin interaction, the role of plexins in the nervous system is not well understood. To gain insight into the functions of plexins in the nervous system, we analyzed spatial and temporal expression patterns of three members of the plexin-A subfamily (plexin-A1, -A2, and -A3) in the developing mouse nervous system by in situ hybridization analysis in combination with immunohistochemistry. We show that the three plexins are differentially expressed in sensory receptors or neurons in a developmentally regulated manner, suggesting that a particular plexin or set of plexins is shared by neuronal elements and functions as the receptor for semaphorins to regulate neuronal development.
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10.1002/1097-0177(20010301)220:3<246::AID-DVDY1112>3.0.CO;2-2
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pubmed_225_20320
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Women who receive little or no prenatal care are at increased risk of adverse pregnancy outcome. Although many of these women are disadvantaged and presumably at increased risk for human immunodeficiency virus (HIV) infection, few data are available to describe risk behaviors and infection prevalence in this population. To better characterize HIV infection in unregistered inner-city parturients in Atlanta, we offered routine voluntary screening for HIV antibody and requested HIV risk-behavior profiles on all unregistered and registered parturients seen at Grady Memorial Hospital from July 1, 1987 to June 30, 1988. Of the 834 unregistered and 7356 registered parturients screened, significantly more unregistered parturients were seropositive on enzyme-linked immunosorbent assay and Western blot testing, 12 (1.4%) versus 26 (0.4%) (odds ratio 4.06; 95% confidence interval 1.93-8.43). Five unregistered and 15 registered parturients were seropositive by repeat enzyme-linked immunosorbent assay testing but were Western blot-negative. Significantly more unregistered parturients reported both a history of intravenous drug use, 4.4 versus 1.5% (odds ratio 3.09; 95% confidence interval 2.10-4.54), and crack cocaine use, 3 versus 0.8% (odds ratio 3.96; 95% confidence interval 2.42-6.44). Significantly more unregistered parturients acknowledged risk factors for HIV infection, 14.3 versus 9.9% (odds ratio 1.46; 95% confidence interval 1.19-1.80). Nearly all registered and 86% of unregistered parturients consented to HIV testing. Nearly all parturients completed HIV risk-behavior questionnaires. These data suggest that unregistered inner-city parturients in Atlanta are at greater risk of being HIV-infected and are more likely to report risk behaviors for infection.
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pubmed_225_20320
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pubmed_529_10058
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Orthopaedic residency education has changed substantially in recent decades because of the imposition of the 80-hour work week, a decrease in quality and quantity of general surgical education, regulations mandating closer trainee supervision, and an expansion of orthopaedic subspecialty rotations. These factors pose a challenge in efforts to prepare competent, confident, cautious, caring, and communicative orthopaedic residents within the traditional 5-year program. Evidence suggests that contemporary graduates are more intelligent, better balanced in life and work, and more in touch with humanistic aspects of medicine than were earlier graduates. Yet insufficient competence and confidence in surgical skills after residency and a lack of "ownership" of patient care have become an increasing concern of educators and trainees. The concept of 10,000 hours of deliberate practice to achieve mastery of a technical skill applies to orthopaedic residency education. A different approach to graduate medical education must address the critical minimum training time required to achieve the necessary skills to support independent medical and surgical practice.
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10.5435/JAAOS-D-17-00240
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pubmed_125_7713
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Background: Brain arteriovenous malformations (AVMs) are a relatively infrequent vascular pathology of unknown etiology that, despite their rarity, cause the highest number of hemorrhagic strokes under the age of 30 years. They pose a challenge to all forms of treatment due to their variable morphology, location, size, and, last but not least, evolving nature. MicroRNAs (miRNAs) are non-coding RNA strands that may suppress the expression of target genes by binding completely or partially to their complementary sequences. Single nucleotide polymorphisms (SNPs), as the name implies, are variations in a single nucleotide in the DNA, usually found in the non-coding segments. Although the majority of SNPs are harmless, some located in the proximity of candidate genes may result in altered expression or function of these genes and cause diseases or affect how different pathologies react to treatment. The roles miRNAs and certain SNPs play in the development and growth of AVMs are currently uncertain, yet progress in deciphering the minutiae of this pathology is already visible. Methods and Results: We performed an electronic Medline (PubMed, PubMed Central) and Google Academic exploration using permutations of the terms: "arteriovenous malformations," "single nucleotide polymorphisms," "microRNA," "non-coding RNA," and "genetic mutations." The findings were then divided into two categories, namely the miRNAs and the candidate gene SNPs associated with AVMs respectively. 6 miRNAs and 12 candidate gene SNPs were identified and discussed. Conclusions: The following literature review focuses on the discoveries made in ascertaining the different implications of miRNAs and candidate gene SNPs in the formation and evolution of brain AVMs, as well as highlighting the possible directions of future research and biological treatment. Abbreviations: ACVRL1/ALK1: activin receptor-like kinase 1; Akt: protein kinase B; ANGPTL4: angiopoietin-like 4; ANRIL: antisense noncoding RNA in the INK4 locus; AVM: arteriovenous malformation; AVM-BEC: arteriovenous malformation brain endothelial cell; BRCA1: breast cancer type 1 susceptibility protein; CCS: case-control study; CDKN2A/B: cyclin-dependent kinase inhibitor 2A/B; CLTC: clathrin heavy chain; DNA: deoxyribonucleic acid; ERK: extracellular signal-regulated kinase; GPR124: probable G-protein coupled receptor 124; GWAS: genome-wide association study; HHT: hereditary hemorrhagic telangiectasia; HIF1A: hypoxia-inducible factor 1A; IA: intracranial aneurysm; ICH: intracranial hemorrhage; Id-1: inhibitor of DNA-binding protein A; IL-17: interleukin 17; MAP4K3: mitogen-activated protein kinase kinase kinase kinase 3; miRNA: microRNA; MMP: matrix metalloproteinase; NFkB: nuclear factor kappa-light-chain of activated B cells; NOTCH: neurogenic locus notch homolog; p38MAPK: p38 mitogen-activated protein kinase; PI3K: phosphoinositide 3-kinase; RBBP8: retinoblastoma-binding protein 8; RNA: ribonucleic acid; SNAI1: Snail Family Transcriptional Repressor 1; SNP: single nucleotide polymorphism; SOX-17: SRY-related HMG-box; TGF-β: transformation growth factor β; TGFR: transformation growth factor receptor; TIMP-4, tissue inhibitor of metalloproteinase 4; TSP-1: thrombospondin-1; UTR: untranslated region; VEGF: Vascular Endothelial Growth Factor; VSMC: vascular smooth muscle cell; Wnt1: Wnt family member 1.
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10.1080/01616412.2020.1796380
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pubmed_990_5824
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The lectin, wheatgerm agglutinin (WGA) conjugated to horseradish peroxidase (HRP), previously was shown to be transported into the central nervous system following application by intranasal irrigation. The current study investigated the hypothesis that uptake of molecules, such as the lectin-conjugate, by olfactory receptor cells would mimic internalization of other substances including odorants. This process would result in both premature death of receptor cells and increased turnover of their precursors, globose basal cells. Tetramethylbenzidine histochemical analysis showed the presence of significant amounts of the lectin-conjugate in both the receptor epithelium and olfactory bulb until at least 2 weeks postintranasal application. Neither supporting nor globose basal cells contained WGA-HRP, suggesting that uptake was primarily into olfactory receptor cells. Cell turnover, assessed by tritiated-thymidine (thymidine) autoradiography, increased both 1 and 2 weeks, but not 3 and 4 weeks, following intranasal irrigation with WGA-HRP. Most of the cells containing thymidine labelling appeared to be globose basal cells, although supporting cells also occasionally exhibited labelling. Survival of either mature or immature receptor cells in the epithelium, indicated by epithelial thickness and cell density of the septal epithelium, also declined following treatment. These data suggest that uptake of substances may result in cell loss from the olfactory epithelium and increased mitotic activity of basal cells.
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10.1002/(sici)1096-9861(19980420)393:4<472::aid-cne6>3.0.co;2-y
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pubmed_386_23942
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Soy protein isolate (SPI) nanoparticles (28-179 nm) were prepared by employing a cold gelation method with a slight modification. The obtained nanoparticles exhibited uniform size distribution and spherical shape with a unique honeycomb-like core structure. Nanoparticle characteristics including size, surface charge and hydrophobicity could be adjustable by changing calcium concentration and environmental pH. Generally, higher calcium concentration and lower pH led to formation of nanoparticles with larger size, lower surface charge and hydrophobicity. Both protein conformation and nanoparticle dissociation studies indicated that calcium likely shielded negative charges on the SPI polypeptide chains, and functioned as a salt-bridge to permit polypeptide chains to approach one another. In this process, calcium favoured the development of β-sheet structures to form SPI aggregates stabilised by hydrogen bonding. These aggregates were then associated to build SPI nano-networks through hydrophobic interactions. In vitro study indicated that the SPI nanoparticles were non-toxic and mainly located in the cytoplasm when uptaken into Caco-2 cells.
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pubmed_386_23942
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pubmed_256_3082
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The learning opportunities presented in nurses' storied accounts of practice are explored. This exploration is achieved through analysis and discussion of three nurse's stories documented in the literature, and uses Benner's (1991) narratives of learning theme as the conceptual framework. The narrative of learning sub themes: being open to experience, liberation, and disillusionment are examined. This examination suggests nurses stories can be used to: discover nursing knowledge, develop shared understandings of what it is to be a nurse, examine nursing's culture and ethics, document interactions for research, teaching and learning, and identify and preserve the practice of nursing. Whereas edited stories from the literature only begin to demonstrate the possibilities for learning that stories offer, through them alternative ways of learning about nursing, exploring nursing practice and developing nursing knowledge are presented.
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10.5172/conu.4.2.56
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pubmed_1089_3352
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OBJECTIVE
To evaluate the feasibility and sustainability of basic obstetric ultrasound training in rural Africa.
METHODS
An 8-week training course, led by UK-based sonographers, was supported by training videos and followed by 10 months of remotely supported scanning in Mandimba, Mozambique. Data were collected prospectively using an Android tablet and the EpiCollect web application.
RESULTS
The study group included 1744 pregnant women: 804 scanned by trainees under direct supervision and 940 scanned by trainees alone. Ultrasound identified 36 (2.1%) twin pregnancies, 230 (13.2%) breech presentations, 83 (4.8%) transverse presentations, and 22 (1.3%) cases of placenta previa. The detection rates for the above features were similar in the 2 groups. A subgroup of 230 (13.2%) women had a follow-up scan and 62 (3.6%) were referred to a doctor; 21 of these women required cesarean delivery.
CONCLUSION
Ultrasound training in a rural setting supported remotely is feasible, efficient, and sustainable. It can help local healthcare workers to screen their prenatal populations for obstetric and neonatal risks, and therefore has the potential to improve outcomes at delivery and provide site-specific epidemiologic data that can be used to develop new healthcare provision strategies.
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pubmed_1089_3352
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pubmed_648_17019
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We argue, based on a study of brain responses to speech sound differences in Japanese, that memory encoding of functional speech sounds-phonemes-are highly abstract. As an example, we provide evidence for a theory where the consonants/p t k b d g/ are not only made up of symbolic features but are underspecified with respect to voicing or laryngeal features, and that languages differ with respect to which feature value is underspecified. In a previous study we showed that voiced stops are underspecified in English [Hestvik, A., & Durvasula, K. (2016). Neurobiological evidence for voicing underspecification in English. Brain and Language], as shown by asymmetries in Mismatch Negativity responses to /t/ and /d/. In the current study, we test the prediction that the opposite asymmetry should be observed in Japanese, if voiceless stops are underspecified in that language. Our results confirm this prediction. This matches a linguistic architecture where phonemes are highly abstract and do not encode actual physical characteristics of the corresponding speech sounds, but rather different subsets of abstract distinctive features.
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10.1016/j.brainres.2020.146664
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pubmed_202_10292
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ECG-gated spin-echo MR images of the chest were obtained in two patients with primary pulmonary hypertension (PPH). In transverse section at the level of the right main pulmonary artery (rPA), flow signals in the rPA were quantitatively evaluated, and the correlations with MR signal intensity of intravascular flow and data of routine clinical examinations and the severity of clinical manifestations were studied. In one case, the signal intensity of flowing blood markedly increased with exacerbation of hypoxemia and other clinical manifestations. However, in the other case with a stable course, the signal intensity of intravascular flow did not change significantly. Increase of flow signal in the rPA can reflect decrease of flow velocity that may be cause by a state of high pulmonary vascular resistance or low cardiac output. Therefore, it is suggested that MRI is a useful modality to evaluate the severity of disturbance of the pulmonary circulation in PPH.
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pubmed_202_10292
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pubmed_1003_2177
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The European Society of Intensive Care Medicine (ESICM) annual congress provided an opportunity for basic scientists and clinicians to share recent findings. In addition to the numerous free communications, several sessions by established speakers were dedicated to state-of-the-art tutorials. As usual, the areas of interest varied widely, reflecting the large array of 'critical illnesses'. Results of clinical trials and experimental findings with recently developed drugs were presented, essentially in the fields of inflammation, sepsis and acute lung injury. It is evident that the benefits of several new compounds observed experimentally need to be confirmed in the clinic. The ESICM congress is a unique opportunity to implement and promote collaborations between European basic scientists and clinicians.
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pubmed_1003_2177
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pubmed_440_21204
|
OBJECTIVE
In this study, we reexamine the mental pain-suicidality link in adolescence, by focusing on mental pain tolerance as a critical factor in explaining youth suicidal behavior.
METHOD
In a series of three studies, participants completed measures of mental pain (tolerance and intensity), emotional regulation, depression, and suicidality. Study 1 included a nonclinical sample of 183 Israeli adolescents. Study 2 included a nonclinical sample of 139 Israeli adolescents, who completed additional measures of self-esteem, optimism, mindfulness, meaning in life, positive affectivity, and life satisfaction. Study 3 included suicidal psychiatric inpatients (N = 24), nonsuicidal psychiatric inpatients (N = 24), and nonclinical adolescents (N = 24).
RESULTS
In Study 1, mental pain tolerance was significantly associated with depression, suicidality, and emotion-regulation skills. In Study 2, mental pain tolerance was significantly associated with measures of psychological resources. In Study 3, we found that suicidal psychiatric inpatients reported significantly lower levels of mental pain tolerance than nonsuicidal psychiatric inpatients and nonclinical adolescents. No significant group difference was found in the reported intensity of mental pain.
CONCLUSIONS
Findings imply that mental pain tolerance may be a better indicator for suicidal behavior during adolescence than reported pain intensity.
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10.1111/sltb.12506
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pubmed_251_18998
|
BACKGROUND
Although protocols have been published for reducing natural rubber latex exposure in medical environments, there are no objective data documenting their effectiveness.
OBJECTIVE
We prospectively studied the impact of a single intervention, substitution of low-allergen-containing latex gloves for high-allergen-containing latex gloves, on latex aeroallergen levels in a single operating room (OR).
METHODS
We sampled OR air on 52 consecutive days, including 33 surgery days and 19 nonsurgery days. On each surgery day all personnel wore either high-allergen gloves (n = 18 days) or low-allergen gloves (n = 15 days). Latex aeroallergen levels (in nanograms per cubic meter) and extractable latex glove allergen contents (in allergen units per milliliter) were measured by inhibition immunoassays. An on-site study monitor recorded the number of gloves used, the total time spent by all patients in the OR each day (OR time), and the total time of all procedures for each day (operating procedure time).
RESULTS
Latex aeroallergen levels during low-allergen glove use days (mean, 1.1 ng/m3; median, 0.9 ng/m3; range, 0.1 to 3.5 ng/m3) were significantly lower than on high-allergen glove use days (mean, 13.7 ng/m3; median, 7.7 ng/m3; range, 2.2 to 56.4 ng/m3) (p < 0.001) but not significantly different from that on nonsurgery days (mean, 0.6 ng/m3; median, 0.3 ng/m3; range, 0.1 to 3.6 ng/m3). Latex aeroallergen levels were strongly correlated with the total number of gloves used on designated high-allergen glove days (r = 0.66, p = 0.003). There was no appreciable day-to-day carryover of latex aeroallergen.
CONCLUSIONS
The substitution of low-allergen-containing latex gloves for high-allergen-containing latex gloves can reduce levels of latex aeroallergen by more than 10-fold in an OR environment.
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10.1016/s0091-6749(96)70157-4
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pubmed_869_6032
|
PURPOSE OF REVIEW
With increasing longevity, altered demographics of the lung cancer population, and preoperative interventions to enhance the efficacy of surgical therapy, increasing numbers of elderly people will present for anesthesia and pulmonary resection.
RECENT FINDINGS
The geriatric population often exhibits wide disparity between chronologic and physiologic senescence which is underscored by data indicating that outcome following lung resection for cancer is influenced more by tumor stage, preoperative functional status and comorbidities than age alone. Nonetheless, the normal process of cardiopulmonary aging can limit the physiological reserve necessary to compensate for perioperative stress even in otherwise healthy elderly patients. Data indicate a relatively favorable risk-benefit relationship for lung resection in the elderly given the poor prognosis for patients undergoing palliative care or chemotherapy or radiation alone. Emerging experience now suggests that minimally invasive surgical techniques for the treatment of lung cancer may parallel conventional thoracotomy in terms of oncologic efficacy while decreasing perioperative morbidity in the elderly.
SUMMARY
The combination of an aging population, recent advances in neoadjuvant therapies, data supporting the oncologic efficacy of resection, and minimally invasive surgical techniques strongly suggests that more elderly patients will be candidates for surgical management of their lung cancer, thus presenting anesthesiologists with unique challenges.
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10.1097/ACO.0b013e32801271fa
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pubmed_686_21153
|
Recently we found that 1-methyldodecanoylindole-2-carboxylic acid (1) and 1-[2-(4-carboxyphenoxy)ethyl]-3-dodecanoylindole-2-carboxylic acid (4) were inhibitors of the cytosolic phospholipase A2alpha (cPLA2alpha)-mediated arachidonic acid release in calcium ionophore A23187-stimulated human platelets with IC50-values of 4.8 microM (1) and 0.86 microM (4). We have now replaced the 3-acyl residue of these compounds by alkylated sulfinyl-, sulfony-, sulfinamoyl-, sulfamoyl-, carbonylamino-, or carbonylaminomethyl-substituents. Structure-activity relationship studies revealed that the pronounced cellular activity of 4 strongly depends on the presence of the 3-acyl moiety. Surprisingly, when testing 4 and its derivatives in an assay with the isolated cPLA2, none of these compounds showed an inhibitory potency at 10 microM indicating that they do not inhibit cPLA2alpha in the cells by a direct interaction with the active site of the enzyme.
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10.1080/14756360500228338
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pubmed_445_15867
|
Goat antibody against pure rabbit pulmonary angiotensin-converting enzyme was used to probe homology of converting enzymes from other species. Immunologically cross-reactive material was found in detergent-solubilized extracts of lung particles from rat, guinea pig, and dog by double immunodiffusion, radioimmunoassay, and inhibition of enzyme activity. No homology was demonstrable with bovine, frog, or chicken lung extracts. Antibodies from different individual goats yielded comparable estimates of homology by immunodiffusion and radioimmunoassay. In contrast, they varied greatly in extent and specificity of their inhibitory action on heterologous enzyme activity. The vasopressor effect of angiotensin I and the vasodepressor effect of bradykinin were diminished and potentiated, respectively, in rats treated with anti-rabbit enzyme antibody. A smaller but significant immune-dependent inhibition of the vasopressor response to angiotensin II was also observed.
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pubmed_445_15867
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pubmed_959_8672
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The M protein of group A streptococci (Strep A) is a major virulence determinant and protective antigen. The N-terminal sequence of the protein defines the more than 200 M types of Strep A and also contains epitopes that elicit opsonic antibodies, some of which cross-react with heterologous M types. Current efforts to develop broadly protective M protein-based vaccines are directed at identifying potential cross-protective epitopes located in the N-terminal regions of cluster-related M proteins for use as vaccine antigens. In this study, we have used a comprehensive approach using the recurrent neural network ABCpred and IEDB epitope conservancy analysis tools to predict 16 residue linear B-cell epitopes from 117 clinically relevant M types of Strep A (~88% of global Strep A infections). To examine the immunogenicity of these epitope-based vaccines, nine peptides that together shared ≥60% sequence identity with 37 heterologous M proteins were incorporated into two recombinant hybrid protein vaccines, in which the epitopes were repeated 2 or 3 times, respectively. The combined immune responses of immunized rabbits showed that the vaccines elicited significant levels of antibodies against all nine vaccine epitopes present in homologous N-terminal 1-50 amino acid synthetic M peptides, as well as cross-reactive antibodies against 16 of 37 heterologous M peptides predicted to contain similar epitopes. The epitope-specificity of the cross-reactive antibodies was confirmed by ELISA inhibition assays and functional opsonic activity was assayed in HL-60-based bactericidal assays. The results provide important information for the future design of broadly protective M protein-based Strep A vaccines.
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10.1016/j.vaccine.2021.01.075
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pubmed_794_10438
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A better understanding of the physical activity (PA) infrastructure in schools, the walkability of neighborhoods close to schools, and the food environments around schools, particularly in rural, socioeconomically challenged areas such as the North-West (NW) of Tasmania, could be important in the wider effort to improve the health of school-age children. Accordingly, this research aimed to assess PA resources, walkability, and food environments in and around schools in three socioeconomically disadvantaged, regional/rural Local Government Areas (LGAs) of Tasmania, Australia. A census of schools (including assessment of the PA infrastructure quality within school grounds), a walkability assessment, and a census of food outlets surrounding schools (through geospatial mapping) were executed. Most of the schools in the study region had access to an oval, basketball/volleyball/netball court, and free-standing exercise equipment. In all instances (i.e., regardless of school type), the quality of the available infrastructure was substantially higher than the number of incivilities observed. Most schools also had good (i.e., within the first four deciles) walkability. Numerous food outlets were within the walking zones of all schools in the study region, with an abundance of food outlets that predominantly sold processed unhealthy food.
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10.3390/ijerph19106238
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pubmed_143_7555
|
Simulating the additive manufacturing process of Ti-6Al-4V is very complex due to the microstructural changes and allotropic transformation occurring during its thermomechanical processing. The α -phase with a hexagonal close pack structure is present in three different forms-Widmanstatten, grain boundary and Martensite. A metallurgical model that computes the formation and dissolution of each of these phases was used here. Furthermore, a physically based flow-stress model coupled with the metallurgical model was applied in the simulation of an additive manufacturing case using the directed energy-deposition method. The result from the metallurgical model explicitly affects the mechanical properties in the flow-stress model. Validation of the thermal and mechanical model was performed by comparing the simulation results with measurements available in the literature, which showed good agreement.
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10.3390/ma12233844
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pubmed_608_9536
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Aphanomyces euteiches is an oomycete pathogen with a broad host-range on legumes that causes devastating root rot disease in many pea-growing countries and especially in France. Genetic resistance is a promising way to manage the disease since consistent QTL controlling partial resistance have been identified in near isogenic lines of pea. However, there are still no resistant pea varieties cultivated in France. This study aimed to evaluate the phenotypic and genetic diversity of A. euteiches populations from the major pea-growing regions in France. A collection of 205 isolates, from soil samples collected in infested pea fields located in five French regions, was established and genotyped using 20 SSR markers. Thirteen multilocus genotypes were found among the 205 isolates which displayed a low genotypic richness (ranged from 0 to 0.333). Two main clusters of isolates were identified using PCoA and STRUCTURE, including a predominant group comprising 88% of isolates and another group representing 12% of isolates mainly from the Bourgogne region. A subset of 34 isolates, representative of the fields sampled, was phenotyped for aggressiveness on a set of resistant and susceptible varieties of four legume hosts (pea, faba bean, vetch, alfalfa). Significant differences in disease severity were found among isolates and three groups of aggressiveness comprising 16, 17, and 2 isolates, respectively, were identified using HCA analysis. A higher diversity in pathogen aggressiveness was observed among isolates from Bourgogne, which included different legumes in its crop history. Little relationship was observed between genetic clusters and pathogenicity in the subset of 34 isolates, as expected using neutral markers. This study provides useful knowledge on the current state of low to moderate diversity among A. euteiches populations before resistant pea varieties are grown in France. New insights and hypotheses about the major factors shaping the diversity and evolution of A. euteiches are also discussed.
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10.3389/fpls.2018.01673
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pubmed_135_27559
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Methylation has a close relationship with immune reactions, metastasis, and cancer cell growth. Additionally, RNA methylation-related proteins have emerged as potential cancer therapeutic targets. The connection between the tumor microenvironment (TME) and methylation-related genes (MRGs) remains unclear. We explored the expression patterns of the MRGs in the genome and transcriptional fields of 796 prostate cancer (PCa) samples using two separate data sets. We identified a relationship between patient clinicopathological characteristics, prognosis, TME cell infiltrating qualities, and different MRG changes, as well as the identification of two distinct molecular groupings. Then, we formed an MRGs model to predict overall survival (OS), and we tested the accuracy of the model in patients with PCa. In addition, we developed a very accurate nomogram to improve the MRG model's clinical applicability. The low-risk group had fewer tumor mutational burden (TMB), greater tumor immune dysfunction and exclusion (TIDE) ratings, fewer mutant genes, and better OS prospects. We discuss how MGRs may affect the prognosis, clinically important traits, TME, and immunotherapy responsiveness in PCa. In order to get a better understanding of MRGs in PCa, we could further explore the prognosis and create more effective immunotherapy regimens to open new avenues.
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10.3389/fphar.2022.1030766
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pubmed_587_19415
|
The effect of trypsin on the separation an subculture of the keratinocytes was investigated in this work. It was found that when 0.25% trypsin was employed for 5 minutes to separate keratinocytes, the number of active keratinocytes and the cells capable of forming colony were higher than those of other experimental conditions. The maximum attached ratio of primary keratinocytes was obtained when skin tissues were treated at 0.05% concentration of trypsin. With the increase of the trypsin concentrations, the attached ratio, attachment rate constant, and colony forming efficiency were all increased. Thus, 0.25% concentration of trypsin was recommended for separating and subculturing the keratinocytes.
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pubmed_587_19415
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pubmed_1103_1699
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The lipid composition of cellular membranes is regulated to maintain membrane fluidity. A key enzyme involved in this process is the membrane-bound stearoyl-CoA desaturase (SCD) which is the rate-limiting enzyme in the cellular synthesis of monounsaturated fatty acids from saturated fatty acids. A proper ratio of saturated to monounsaturated fatty acids contributes to membrane fluidity. Alterations in this ratio have been implicated in various disease states including cardiovascular disease, obesity, non-insulin-dependent diabetes mellitus, hypertension, neurological diseases, immune disorders, and cancer. The regulation of stearoyl-CoA desaturase is therefore of considerable physiological importance and its activity is sensitive to dietary changes, hormonal imbalance, developmental processes, temperature changes, metals, alcohol, peroxisomal proliferators, and phenolic compounds. Two mouse and rat SCD genes (SCD1 and SCD2) and a single human SCD gene have been cloned and characterized. In the past several years we have studied the dietary influences on the genetic expression of the mouse stearoyl-CoA desaturase. The expression of the mouse SCD genes is regulated by polyunsaturated fatty acids and cholesterol at the levels of transcription and mRNA stability. Promoter elements that are responsible for the polyunsaturated fatty acid repression colocalize with the promoter elements for SREBP-mediated regulation of the SCD genes. It is the goal of this review to provide an overview of the genetic regulation of the stearoyl-CoA desaturase in response to dietary polyunsaturated fatty acids and cholesterol.
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pubmed_1103_1699
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pubmed_222_16167
|
Using brain microdialysis, it was demonstrated that the release of 5-hydroxytryptamine (5-HT) in the central nucleus of the amygdala is under inhibitory control of somatodendritic and postsynaptic 5-HT1A receptors. Systemic administration of flesinoxan, a selective 5-HT1A receptor agonist, significantly reduced the extracellular levels of 5-HT in the central nucleus of the amygdala. This effect could be completely antagonized by the 5-HT1A receptor antagonist N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)-N-(2-pyridyl)cyclohexane carboxamine trihydrochloride (WAY 100635). Local administration of these compounds by reversed microdialysis into the raphe nuclei revealed that extracellular 5-HT levels in the central nucleus of the amygdala can be regulated through 5-HT1A receptors in the caudal linear raphe nucleus, but not in the dorsal and median raphe nuclei. Interestingly, administration of flesinoxan into the central nucleus of the amygdala also decreased dialysate 5-HT levels both locally and in the caudal linear raphe nucleus. The former effect could be blocked by pretreatment with WAY 100635 when applied into the central nucleus of the amygdala, but not when applied into the caudal linear raphe nucleus. These data provide circumstantial evidence for the existence of a 5-HT1A receptor mediated feedback loop from the central nucleus of the amygdala to the caudal linear raphe nucleus.
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10.1016/s0014-2999(97)01141-2
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pubmed_1067_11001
|
BACKGROUND
Many anomalies and variants in vascular anatomy have been reported in relation to the anterior cerebral artery (ACA).
PATIENTS AND METHODS
We encountered an apparently novel anomaly in a 30-year-old man admitted for disturbance of consciousness following a traffic accident. Computed tomography revealed an acute subdural hematoma and subarachnoid hemorrhage.
RESULTS AND CONCLUSIONS
No vascular abnormalities related to the hemorrhage were detected by conventional angiography, so we concluded that the bleeding was of traumatic origin. Anomalous origin of the ACA was disclosed incidentally, with both A1 segments arising from the right internal carotid artery; no normal A1 segment of the left ACA was visualized. We discuss possible bases for this anomalous origin.
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10.1017/s0317167100004285
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pubmed_948_18000
|
With the use of the human basophil histamine release assay, 5-aryl-2-amino[1,2,4]triazolo[1,5-c]pyrimidines were found to be active as mediator release inhibitors. These compounds were prepared by reacting arylamidines with sodium ethyl formylacetate or with ethyl propiolate to give pyrimidinones. Treatment with phosphorus oxychloride gave a chloropyrimidine, which was converted to a hydrazinopyrimidine with hydrazine. Cyclization, using cyanogen bromide, gave the triazolo[1,5-c]pyrimidines, after a Dimroth rearrangement. Following a structure-activity evaluation, the 5-[3-(trifluoromethyl)phenyl]-2-amino (8-10), 5-(3-bromophenyl)-2-amino (8-13), 5-[3-(difluoromethoxy)-phenyl]-2-amino (8-11), and 5-(4-pyridinyl)-2-amino (6-7) compounds were found to have the best activity. They were chosen for further pharmacological and toxicological study.
|
10.1021/jm00166a023
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pubmed_542_1613
|
The structure of the ripple phase in multilamellar DPPC liposomes was studied by measuring electron spin resonance (ESR) spectra of the stearic acid spin probe (16-SASL). The spectrum observed in the P beta' phase is explained in terms of the superposition of ordered- and disordered-type spectra. This fact suggests the existence of a nonhomogeneous structure in the P beta' phase, i.e., the coexistence of the ordered region present in the L beta' phase and the disordered region present in the L alpha phase. The fluidity of acyl chains in both regions and the intensity ratio of the disordered-type spectra to the total intensity were estimated from the ESR spectra at various temperatures. The fluidity of both regions did not exhibit remarkable temperature dependence. On the other hand, the intensity ratio showed almost similar temperature dependence of the partitioning of the TEMPO observed by ESR measurement and of the enthalpy curve by DSC measurement, that is, the intensity ratio value increases slowly near the pretransition temperature, is almost constant in the P beta' phase, and increases abruptly at the main transition temperature with temperature. The proportion of the disordered region is estimated to be about one-fifth to the total region in the P beta' phase. Based upon the above results, a model for the ripple structure is proposed.
|
10.1016/0005-2736(88)90364-1
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pubmed_461_2396
|
Aging is a biological process being experienced. The experience of ageing is associated with disappointment and renuciation. Thus, aging is a task which can be mastered in different ways.--It is asserted that there is an ageing having a social sense.--It is demonstrated by some parameters which advancements and which hindrances may play a role in ageing as well as which defective developments may be possible. The traditional norms and ideas from former generations as well as the social evaluation of age have to be taken into consideration when an approach to the problems of aging is designed.--The different situation of the sexes is briefly outlined.--The physician can help best if he himself is able to cope with his own ageing.
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pubmed_461_2396
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pubmed_628_16584
|
BACKGROUND AND OBJECTIVE
Endomyocardial biopsy is the gold standard for monitoring rejection in cardiac recipients. The death rate due to rejection with this invasive method is 5-6 % in the first postoperative year. The aim of this retrospective data analysis from cardiac recipients was to prove the diagnostic reliability of a non-invasive electrophysiological method for rejection monitoring.
PATIENTS AND METHODS
We daily analyzed the QRS-complex amplitude of the intramyocardial electrogram, which we received over a period from one year via a pacemaker with a telemetric capability. The diagnostic guideline for a suspected rejection was the reduction of the QRS-complex amplitude by more than 8 %. Out of 734 patients 558 were included in the study. Biopsy was only performed when the non-invasive rejection monitoring data (QRS-complex amplitude plus echocardiography) showed a discrepancy for rejection.
RESULTS
None of the patients died due to rejection, 273 at least once underwent a biopsy, and 285 never had a biopsy. The method reached a sensitivity of 0.9777, a specificity of 0.9634, a negative predictive value of 0.9850, and a positive predictive value of 0.9459.
CONCLUSION
Daily electrophysiological non-invasive monitoring of rejection seems to be superior to endomyocardial biopsy. Death of patients due to rejection can be minimised. The number of necessary biopsies can be drastically reduced when compared to the usual number performed.
|
10.1055/s-2001-18135
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pubmed_460_19653
|
A 47-year-old man presented with meatal bleeding. Visual inspection revealed papillary meatal tumors at 5 and 7 o'clock without other genital warts. These lesions were completely resected, and the histological diagnosis was condyloma acuminata. After 2 months, recurrence of warts was not observed macroscopically in the genital area, including the urethral meatus. However, urethroscopy revealed a papillary tumor in the navicular fossa. This lesion was removed and pathological examination revealed that it was also a condyloma acuminatum.
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pubmed_460_19653
|
pubmed_1138_21203
|
Between January 1, 1984 and December 31, 1991, 471 cadaver renal transplants were performed. We reviewed 130 transplants, which were biopsied 30 minutes to 1 hour after the establishment of renal allograft blood flow. Analysis showed a significant difference in 2-year graft survival rate between the groups with and without arteriosclerosis (71.8% versus 65.9%, p < 0.05). Arteriosclerotic changes were noted more frequently in biopsies from older donors (37 versus 28 years, p < 0.005). There was also a difference in ischemic time between the groups with and without tubular degeneration (30.1 hours versus 26.7 hours, p < 0.02), which did not correlate with the need for dialysis in the perioperative period (48% versus 49%, p > 0.8).
|
10.1016/s0022-5347(17)35018-8
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pubmed_199_11093
|
The importance of syphilis serological tests demands that laboratory reports are reliable. Internal quality control applied to the organisation of a syphilis serology service improves laboratory bench performance and reporting. Described here are internal quality control procedures of a department that serves a genitourinary medicine clinic and conducts 70 000 tests a year to investigate for syphilis.
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10.1136/sti.61.2.88
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pubmed_238_20405
|
BACKGROUND
Obstructive sleep apnea (OSA) and insomnia are commonly co-occurring conditions that amplify morbidity and complicates the management of affected patients. Unfortunately, previous research provides limited guidance as to what constitutes the best and most practical management approach for this comorbid patient group. Some preliminary studies show that when cognitive behavioral insomnia therapy (CBT-I) is combined with standard OSA therapies for these patients, outcomes are improved. However, the dearth of trained providers capable of delivering CBT-I has long served as a pragmatic barrier to the widespread use of this therapy in clinical practice. The emergence of sophisticated online CBT-I (OCBT-I) programs could improve access, showing promising reductions in insomnia severity. Given its putative scalability and apparent efficacy, some have argued OCBT-I should represent a 1st-stage intervention in a broader stepped care model that allocates more intensive and less assessable therapist-delivered CBT-I (TCBT-I) only to those who show an inadequate response to lower intensity OCBT-I. However, the efficacy of OCBT-I as a 1st-stage therapy within a broader stepped care management strategy for insomnia comorbid with OSA has yet to be tested with comorbid OSA/insomnia patients.
METHODS/DESIGN
This dual-site randomized clinical trial will use a Sequential Multiple Assignment Randomized Trial (SMART) design to test a stepped care model relative to standard positive airway pressure (PAP) therapy and determine if (1) augmentation of PAP therapy with OCBT-I improves short-term outcomes of comorbid OSA/insomnia and (2) providing a higher intensity 2nd-stage CBT-I to patients who show sub-optimal short-term outcomes with OCBT-I+PAP improves short and longer-term outcomes. After completing baseline assessment, the comorbid OSA/insomnia patients enrolled will be randomized to a 1st-stage therapy that includes usual care PAP + OCBT-I or UC (usual care PAP + sleep hygiene education). Insomnia will be reassessed after 8 weeks. OCBT-I recipients who meet "remission" criteria (defined as an Insomnia Severity Index score < 10) will continue PAP but will not be offered any additional insomnia intervention and will complete study outcome measures again after an additional 8 weeks and at 3 and 6 month follow-ups. OCBT-I recipients classified as "unremitted" after 8 weeks of treatment will be re-randomized to a 2nd-stage treatment consisting of continued, extended access to OCBT-I or a switch to TCBT-I. Those receiving the 2nd-stage intervention as well as the UC group will be reassessed after another 8 weeks and at 3- and 6-month follow-up time points. The primary outcome will be insomnia remission. Secondary outcomes will include subjective and objective sleep data, including sleep time, sleep efficiency, fatigue ratings, PAP adherence, sleepiness ratings, sleep/wake functioning ratings, and objective daytime alertness.
DISCUSSION
This study will provide new information about optimal interventions for patients with comorbid OSA and insomnia to inform future clinical decision-making processes.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT03109210 , registered on April 12, 2017, prospectively registered.
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10.1186/s13063-022-06753-4
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pubmed_80_216
|
Pancreatic ductal adenocarcinoma (PDAC) is notorious for its poor survival and resistance to conventional therapies. PI3K signaling is implicated in both disease initiation and progression, and specific inhibitors of selected PI3K p110 isoforms for managing solid tumors are emerging. We demonstrate that increased activation of PI3K signals cooperates with oncogenic Kras to promote aggressive PDAC in vivo. The p110γ isoform is overexpressed in tumor tissue and promotes carcinogenesis via canonical AKT signaling. Its selective blockade sensitizes tumor cells to gemcitabine in vitro, and genetic ablation of p110γ protects against Kras-induced tumorigenesis. Diet/obesity was identified as a crucial means of p110 subunit up-regulation, and in the setting of a high-fat diet, p110γ ablation failed to protect against tumor development, showing increased activation of pAKT and hepatic damage. These observations suggest that a careful and judicious approach should be considered when targeting p110γ for therapy, particularly in obese patients.
|
10.1073/pnas.1813012116
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pubmed_50_23720
|
The aim of this study was to use exponential random graph models (ERGMs) to explain networks of movement of backyard chickens in provinces which had been hotspots for avian influenza outbreaks in Thailand during 2004-2005. We used structured questionnaires to collect data for the period January to December 2009 from participants who were involved in the backyard chicken farming network in three avian influenza hotspots (Ratchaburi, Suphan Buri, and Nakhon Pathom provinces) in Thailand. From 557 questionnaires, we identified nodes, points of entry and exit from nodes, and activities relating to backyard chicken farming and movement of chickens, and generated ERGMs based on non-festive periods (Model 1) and the Chinese New Year period (Model 2). In Model 1, k-star (the central node is connected to k other nodes) connections were predominant (P < 0.001). In Model 2, the frequency of movement increased by 10.62 times, k-star connections were still predominant (P < 0.001), and the model was scale-free. Hubs were formed from owners/observers in the arenas/training fields, farmers who raised chickens for consumption only, and traders. In conclusion, our models indicated that, if avian influenza was introduced during non-festive periods, the authorities would need to regularly restrict the movement of chickens. However, during high-frequency periods of movement of backyard chickens, authorities would also need to focus on the network hubs. Our research can be used by the relevant authorities to improve control measures and reduce the risk or lessen the magnitude of disease spread during an avian influenza epidemic.
|
10.1016/j.prevetmed.2018.07.015
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pubmed_595_14403
|
We described the use of block copolymer micelles as building blocks for the incorporation of water-insoluble photochromic species of azobenzene and the fabrication of multilayer films by alternating the deposition of the block copolymer micelles of poly(styrene-b-acrylic acid), incorporating azobenzene and poly(diallyl-dimethylammonium chloride). The azobenzene incorporated into the block copolymer micelles can undergo a reversible photoisomerization under the irradiation of UV and visible light sources. An interesting finding is that the photoisomerization of the azobenzene in the multilayer film is faster than it is in its normal solid film, but very similar to that in its diluted solution. Furthermore, the amount of azobenzene incorporated into the micelles can influence the photoisomerization rates in the films. Therefore, we expect that the block copolymer micelles may provide a proper microenvironment for the photoisomerization of azobenzene and the as-prepared polyelectrolyte/block copolymer micelle thin films will be useful for photoswitching materials.
|
10.1021/la053441a
|
pubmed_186_1074
|
The transcription factor nuclear factor-κB (NF-κB) signaling pathway is crucial in B-cell physiology. One key molecule regulating this pathway is the serine/threonine kinase TAK1 (MAP3K7). TAK1 is responsible for positive feedback mechanisms in B-cell receptor signaling that serve as an NF-κB activation threshold. This study aimed to better understand the correlation between TAK1-mediated signaling and B-cell development and humoral immune responses. Here we showed that a B-cell conditional deletion of TAK1 using mb1-cre resulted in a dramatic elimination of the humoral immune response, consistent with the absence of the B-1 B-cell subset. When monitoring the self-reactive B-cell system (the immunoglobulin hen egg lysozyme/soluble hen egg lysozyme double-transgenic mouse model), we found that TAK1-deficient B cells exhibited an enhanced susceptibility to cell death that might explain the disappearance of the B1 subset. In contrast, these mice gained numerous marginal zone (MZ) B cells. We consequently examined the basal and B-cell receptor-induced activity of NF-κB2 that is reported to regulate MZ B-cell development, and demonstrated that the activity of NF-κB2 increased in TAK1-deficient B cells. Thus, our results present a novel in vivo function, the negative role of TAK1 in MZ B-cell development that is likely associated with NF-κB2 activation.
|
10.1038/icb.2016.44
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pubmed_332_4243
|
BACKGROUND
Handover of patient information represents a critical time period during a patient's hospitalisation. While recent guidelines promote standardised communication during these patient care transitions, significant variability in structure and practice persists among hospitals and providers.
METHODS
The authors surveyed internal medicine residents regarding handover practices before and after introduction of a structured, web-based handover application. The handover application standardised patient data in a format suitable for both patient handovers and day-to-day patient management.
RESULTS
A total of 80 residents were surveyed prior to the intervention (80% response rate) and 161 residents during the intervention (average 68% response rate for all surveys distributed). At baseline, residents perceived deficits in handover practices related to the variability of information transferred and correlated that variability to near-miss events. After introduction of the handover application, 100% of handovers contained an updated problem list, active medications, and code status (compared to <55% at baseline, p<0.01); residents perceived approximately half as many near-miss events on call (31.5% vs 55%; p=0.0341) and were twice as likely to respond that they were confident or very confident in their patient handovers compared to traditional practices (93% vs 49%; p=0.01).
CONCLUSION
Standardisation of information transmitted during patient handovers through the use of a structured, web-based application led to consistent transfer of vital patient information and was associated with improved resident confidence and fewer perceived near-miss events on call.
|
10.1136/bmjqs-2011-000308
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pubmed_913_3869
|
In cats, under Dial anaesthesia, Renshaw cells were excited by microiontophoretic applications of acetylcholine (ACh), aspartate, and glutamate. Substance P, in small doses (10-30 nA), selectively abolished the responses to ACh, leaving the discharges evoked by the amino acids unchanged or enhanced. Higher doses (greater than 50 nA) depressed all responses, but those evoked by amino acids went down last and recovered sooner. By contrast, neither synaptic responses to ventral root stimulation nor spontaneous discharges were affected by substance P, presumably owing to the high efficacy of synaptic transmission and the presence of diffusion barriers around junctional sites.
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10.1139/y77-129
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pubmed_1075_12886
|
A. schaalii is a rare uropathogen. We report urosepsis with Actinobaculum schaalii detected serendipitously in blood and urine culture in a 79-year-old with urinary tract obstruction. This paper illuminates the flaws in our current system in detecting A. schaalii and raises awareness among clinicians and laboratory teams.
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10.1155/2012/468516
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pubmed_877_82
|
Amitifadine, the only drug ever clinically tested in Phase 3 for treating depression, is a triple reuptake inhibitor (TRI) that simultaneously interacts with human monoamine transporters (MATs) including hSERT, hNET and hDAT. This novel multi-target strategy improves drug efficacy and reduces the toxic side effects of drugs. However, the binding modes accounting for amitifadine's polypharmacological mode of action are still elusive, and extensive exploration of the amitifadine-target interactions between amitifadine and MATs is urgently needed. In this study, a total of 0.63 μs molecular dynamics (MD) simulations with an explicit solvent as well as endpoint binding free energy (BFE) calculation were carried out. MD simulation results identified a shared binding mode involving eleven key residues at the S1 site of MATs for the binding of amitifadine, and the results of the BFE calculations were in good agreement with experimental reports. Moreover, by analyzing the per-residue energy contribution variation at the S1 site of three MATs and additional cross-mutagenesis simulations, the variation in the inhibition ratio of amitifadine between hSERT and two other MATs was discovered to mainly come from non-conserved residues (Y95, I172 and T439 in hNET and Y95, I172, A169 and T439 in hDAT). As the rational inhibition ratio of multi-target drugs among various therapeutic targets was found to be the key to their safety and tolerance, the findings of this study may further facilitate the rational design of more potent but less toxic multi-target antidepressant drugs.
|
10.1039/c7cp07869b
|
pubmed_1048_14651
|
The sizes of paralogues-gene families produced by ancestral duplication-are known to follow a power-law distribution. We examine the size distribution of gene sets or gene families where genes are grouped by a similar function or share a common property. The size distribution of Human Gene Nomenclature Committee (HGNC) gene sets deviate from the power-law, and can be fitted much better by a beta rank function. We propose a simple mechanism to break a power-law size distribution by a combination of splitting and merging operations. The largest gene sets are split into two to account for the subfunctional categories, and a small proportion of other gene sets are merged into larger sets as new common themes might be realized. These operations are not uncommon for a curator of gene sets. A simulation shows that iteration of these operations changes the size distribution of Ensembl paralogues and could lead to a distribution fitted by a rank beta function. We further illustrate application of beta rank function by the example of distribution of transcription factors and drug target genes among HGNC gene families.
|
10.1098/rsos.160275
|
pubmed_950_3015
|
An investigation to optimize the application of the third-generation charge optimized many-body (COMB3) interatomic potential and associated input parameters was carried out through the study of solid-liquid interactions in classical molecular dynamics simulations. The rates of these molecular interactions are understood through the wetting rates of water nano-droplets on a bare copper (111) surface. Implementing the Langevin thermostat, the influence of simulation time step, the number of atoms in the system, the frequency at which charge equilibration is performed, and the temperature relaxation rate are all examined. The results indicate that time steps of 0.4 fs are possible when using longer relaxation times for the system temperature, which is almost double the typical time step used for reactive potentials. The use of the charge equilibration allows for a fewer atomic layers to be used in the Cu slab. In addition, charge equilibrium schemes do not need to be performed every time step to ensure accurate charge transfer. Interestingly, the rate of wetting for the nanodroplets is dominantly dependent on the temperature relaxation time, which is predicted to significantly change the viscosity of the water droplets. This work provides a pathway for optimizing simulations using the COMB3 reactive interatomic potential.
|
10.1063/5.0009011
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pubmed_211_18843
|
OBJECTIVE
To evaluate the characteristics of high frequency (HF) components of the early cortical somatosensory evoked potentials (SEPs).
METHODS
We recorded 8-channel SEPs from the frontal and left centro-parietal scalp after right median nerve stimulation with a wide band-pass (0.5-2000 Hz) and digitized at 40 kHz sampling rate in 12 healthy subjects. HF components were analyzed after digital band-pass filtering (300-1000 Hz). The power spectrum was obtained by a maximum entropy method.
RESULTS
HF oscillations (maximum power at 600-800 Hz) consisting of 5 to 8 peaks were discriminated from the preceding P14 far-field in all cases and their phases were reversed between the frontal and contralateral parietal regions. In addition, in subjects with a high amplitude central P22 potential in original wide-band recordings, a single HF oscillation with a maximum at the central region was present. Furthermore, this component showed no phase reversal over the centro-parietal area.
CONCLUSION
We therefore conclude that HF oscillations are superimposed not only on the tangential N20-P20 but on the radial P22 potential, and are generated from both tangential (area 3b) and radial (area 1) current sources.
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10.1016/s0168-5597(98)00032-x
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pubmed_710_25801
|
INTRODUCTION
The intense training and occupational demands of military personnel place the individual at risk of serious injury. When they do occur, serious personal injuries (SPIs) can lead to medical discharge, mission compromise, and ongoing recurrence of problems. Prior to the implementation of any minimization strategies, an understanding of the causes of SPIs requires development. The aim of this study was to analyze the incidence rates and patterns of SPIs within the Australian Regular Army (ARA) and Australian Army Reserve (ARES).
METHODS
Data for a 2-year period were obtained through the Work Health, Safety, Compensation, and Reporting database of the Australian Department of Defence. Records of SPIs were extracted, with details including: (a) the activity being performed when the injury was suffered; (b) the body location of injury; (c) the nature of injury; and (d) the mechanism of injury. Results were reported as number of SPIs and converted to SPIs/100 full-time equivalent (FTE) years of service.
RESULTS
In total, 507 SPIs were reported over the two-year period (ARA = 466; ARES = 41). SPIs most commonly: occurred during combat training (n = 80; 0.13 SPIs/100 FTE years) and physical training (n = 66; 0.10 SPIs/100 FTE years); affected the head (n = 63; 0.10 SPIs/100 FTE years) and shoulders (n = 57; 0.09 SPIs/100 FTE years); and comprised fractures (n = 199; 0.19 SPIs/100 FTE years) and soft-tissue injuries (n = 103; 0.16 SPIs/100 FTE years). The most common mechanism of injury was falls (n = 132; 0.21 SPIs/100 FTE years) or contact with objects (n = 114; 0.18 SPIs/100 FTE years). When adjusted for service time, ARES personnel were found to report SPIs more frequently than ARA personnel (0.87 vs. 0.79/100 FTE years, respectively) giving an injury risk ratio (ARA:ARES) of 0.91 [95% CI = 0.66-1.25].
CONCLUSIONS
Despite higher absolute numbers of SPIs occurring in ARA, ARES in fact report similar rates of SPIs when adjusted for service time. The natures and mechanisms of SPIs are also similar for both service types and therefore should be the focus of targeted programs to reduce such injuries.
|
10.1093/milmed/usz370
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pubmed_130_1426
|
Guillain-Barre Syndrome (GBS) is an acute inflammatory polyradiculoneuropathy which can lead to rapid neuromuscular respiratory failure, with an estimated annual incidence of 1-2 per 100,000 person-years. Even though cranial nerve involvement is known to occur in GBS, radiological correlation on neuroimaging studies are less frequently reported in pediatric population. We hereby report the case of a 14-year-old boy with acute motor axonal neuropathy variant of GBS, who had extensive contrast enhancement of multiple cranial nerves on Magnetic Resonance Imaging brain, associated with clinicoradiological dissociation on presentation.
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10.1097/CND.0000000000000366
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pubmed_1135_5702
|
OBJECTIVE
This guideline summarizes the quality of the evidence to date and provides a reasonable approach to the diagnosis, evaluation and treatment of the hypertensive disorders of pregnancy (HDP).
EVIDENCE
The literature reviewed included the previous Society of Obstetricians and Gynaecologists of Canada (SOGC) HDP guidelines from 2008 and their reference lists, and an update from 2006. Medline, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Registry of Controlled Trials (CCRCT) and Database of Abstracts and Reviews of Effects (DARE) were searched for literature published between January 2006 and March 2012. Articles were restricted to those published in French or English. Recommendations were evaluated using the criteria of the Canadian Task Force on Preventive Health Care and GRADE.
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pubmed_1135_5702
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pubmed_200_18495
|
Morning hypertension (HTN) and nocturnal non-dipping (ND) are closely associated with target organ damage and cardiovascular events. However, their importance in diabetics with advanced renal disease is unclear. We evaluated the relationships of morning HTN and ND with estimated glomerular filtration rate (eGFR) and proteinuria, and determined the risk of morning HTN and ND according to presence of diabetes mellitus (DM) and chronic kidney disease (CKD) stage. A total of 1312 patients, including 439 with diabetes, were prospectively recruited at 21 centers in Korea. All patients had HTN and an eGFR of 15-89 ml min(-1) per 1.73 m(2). Ambulatory 24-h blood pressure was assessed. The rates of morning HTN (25.2% vs. 13.6%, P<0.001) and ND (58.2% vs. 48.2%, P=0.002) were higher in diabetics than in non-diabetics. eGFR was correlated with ND in all patients (P<0.05) and with morning HTN only in non-diabetics (P=0.005). Proteinuria was related to ND in all patients (P<0.05) and to morning HTN only in diabetics (P=0.001). In a regression analysis, the risk of morning HTN was 2.093 (95% confidence interval (95% CI): 1.070-4.094) for the DMCKD2 group, 1.634 (95% CI: 1.044-2.557) for the CKD3-4-only group and 2.236 (95% CI: 1.401-3.570) for the DMCKD3-4 group compared with the CKD2-only group. The risk of ND was high for stage 3-4 CKD: 1.581 (95% CI: 1.180-2.120) for non-diabetics and 1.842 (95% CI: 1.348-2.601) for diabetics. Diabetics showed higher rates of morning HTN, ND and uncontrolled sustained HTN compared with non-diabetics with CKD of the same stages.
|
10.1038/hr.2015.89
|
pubmed_983_3410
|
Gyrodactylus salmonis (Yin et Sproston, 1948) isolates collected from feral rainbow trout, Oncorhynchus mykiss (Walbaum) in Veracruz, southeastern Mexico are described. Morphological and molecular variation of these isolates to G. salmonis collected in Canada and the U.S.A. is characterised. Morphologically, the marginal hook sickles of Mexican isolates of G. salmonis closely resemble those of Canadian specimens - their shaft and hook regions align closely with one another; only features of the sickle base and a prominent bridge to the toe permit their separation. The 18S sequence determined from the Mexican specimens was identical to two variable regions of SSU rDNA obtained from a Canadian population of G. salmonis. Internal transcribed spacer (ITS) regions (spanning ITS1, 5.8S and ITS2) of Mexican isolates of G. salmonis are identical to ITS sequences of an American population of G. salmonis and to Gyrodactylus salvelini Kuusela, Ziętara et Lumme, 2008 from Finland. Analyses of the ribosomal RNA gene of Mexican isolates of G. salmonis show 98-99% similarity to those of Gyrodactylus gobiensis Gläser, 1974, Gyrodactylus salaris Malmberg, 1957, and Gyrodactylus rutilensis Gläser, 1974. Mexican and American isolates of G. salmonis are 98% identical, as assessed by sequencing the mitochondrial cox1 gene. Oncorhynchus mykiss is one of the most widely-dispersed fish species in the world and has been shown to be an important vector for parasite/disease transmission. Considering that Mexican isolates of G. salmonis were collected well outside the native distribution range of all salmonid fish, we discuss the possibility that the parasites were translocated with their host through the aquacultural trade. In addition, this study includes a morphological review of Gyrodactylus species collected from rainbow trout and from other salmonid fish of the genus Oncorhynchus which occur throughout North America.
|
10.1016/j.vetpar.2011.11.005
|
pubmed_757_14909
|
Secondary central nervous system (SCNS) involvement is an infrequent but universally fatal event in diffused large B-cell lymphoma. The occurrence rate of SCNS involvement is approximately 5% but comes with a poor prognosis ever after. However, existing risk models to predict the incidence and prognosis of these patients with SCNS involvement lack both efficiency and accuracy. Controversy has also been reported regarding which risk factor may best identify the population with a high CNS relapse rate. In this study, we retrospectively analyzed 831 patients with diffused large B-cell lymphoma, diagnosed between March 2008 and June 2018 in Tianjin Medical University Cancer Institute and Hospital, Beijing Cancer Hospital, and Cancer Hospital of The University of Chinese Academy of Science. Risk factors and nomogram were identified and established based on Fine and Gray's competing risk analysis. Among these patients, 55 (6.6%) of them eventually developed SCNS involvement. The 1- and 2-year incidence for SCNS involvement were 3.9% and 4.7%, respectively. The median time from de novo diagnosis to CNS relapse was 8 months, and the median overall survival of these patients was 28 months. Considering the competing mortality before SCNS involvement, Fine and Gray's competing risk model was performed to analyze the characteristics related to SCNS involvement, and identified risk factors as the multiple extranodal involvements, elevated LDH and AMC level, and the involvement of breast, adrenal gland/kidney, pulmonary and bone. Corresponding factors were integrated into the competing nomogram for SCNS involvement (c-index = 0.778). In conclusion, we present the first predictive nomogram to evaluate the risk to develop SCNS involvement in de novo DLBCL patients, which may help in both prognostic evaluation and clinical decision for this subgroup.
|
10.1002/hon.2928
|
pubmed_682_18391
|
RATIONALE AND OBJECTIVES
Our objective was to identify factors impacting false positive recalls in screening mammography.
MATERIALS AND METHODS
We retrospectively reviewed our screening mammography database from August 31, 2015 to September 30, 2016, including full field digital mammograms (FFDM) and digital breast tomosynthesis (DBT) mammograms. False positive (FP) exams were defined as Breast Imaging-Reporting and Data System (BI-RADS) 1 or 2 assessments at diagnostic imaging with 1 year cancer-free follow-up, Breast Imaging-Reporting and Data System 3 assessment at diagnostic imaging with 2 years cancer free follow-up, or biopsy with benign pathology. True positives were defined as malignant pathology on biopsy or surgical excision. We evaluated the association of FP recalls with multiple patient-level factors and imaging features.
RESULTS
A total of 22,055 screening mammograms were performed, and 1887 patients were recalled (recall rate 8.6%). Recall rate was lower for DBT than full field digital mammograms (8.0% vs 10.6%, p < 0.001). FP results were lower if prior mammograms were available (90.8% vs 95.8%, p = 0.02), and if there was a previous benign breast biopsy (87.6% vs 92.9%, p = 0.01). Mean age for the FP group was lower than the true positive group (56.1 vs 62.9 years, p < 0.001). There were no significant differences in FP recalls based on history of high-risk lesions, family history of breast or ovarian cancer, hormone use, breast density, race, or body mass index.
CONCLUSION
FP recalls were significantly less likely with DBT, in older women, in patients with prior mammograms available for comparison, and in patients with histories of benign breast biopsy. This study supports the importance of using DBT in the screening setting and obtaining prior mammograms for comparison.
|
10.1016/j.acra.2019.01.020
|
pubmed_1070_2081
|
Fluorescence imaging of nitric oxide (NO) in vitro and in vivo is essential to developing our understanding of the role of nitric oxide in biology and medicine. Current probes such as diaminofluorescein depend on reactions with oxidized NO products, but not with nitric oxide directly, and this limits their applicability. Here we report the formation of an imaging probe for nitric oxide by coordinating the highly fluorescent chemical 4-methoxy-2-(1H-naphtho[2,3-d]imidazol-2-yl)phenol (MNIP) with Cu(II). The coordination compound MNIP-Cu reacts rapidly and specifically with nitric oxide to generate a product with blue fluorescence that can be used in vitro and in vivo. In the present study MNIP-Cu was used to reveal nitric oxide produced by inducible nitric oxide synthase in lipopolysaccharide (LPS)-activated macrophages (Raw 264.7 cells) and by endothelial nitric oxide synthase in endothelial cells (HUVEC). MNIP-Cu was also used to evaluate the distribution of nitric oxide synthesis in a model of acute liver injury induced by LPS and d-galactosamine in mice. The results demonstrate that MNIP-Cu can act as a novel fluorescent probe for nitric oxide and has many potential applications in biomedical research.
|
10.1016/j.freeradbiomed.2008.08.016
|
pubmed_1037_2922
|
In this work, we present the analytical solutions of Dirac equation for modified Kratzer potential in the pseudospin and spin symmetry limits using the formula method. The energies of the pseudospin and spin symmetry limit are obtained analytically and numerically. The numerical values are compared with those obtained in literature. Furthermore, we study the thermodynamic properties of some diatomic molecules within the nonrelativistic spin symmetry limits.
|
10.1016/j.heliyon.2021.e08023
|
pubmed_369_13112
|
BACKGROUND
Diabetes is an illness with multiple quality indicators. This retrospective cohort study sought to determine if interventions directed at physicians to target improvements in hemoglobin A1c (HgA1c) quality indicators had collateral benefits on similarly measured low-density lipoprotein (LDL) indicators.
METHODS
We initially analyzed the primary care diabetic patient electronic databases from 2008 (N = 16,503) and 2010 (N = 23,040). We then identified and selected for the study the cohort of patients who appeared in both databases (N = 11,288) and analyzed various measures of process and outcomes.
RESULTS
Mean HgA1c decreased from 7.34% to 7.21% (P < .0001). Mean LDL level also improved from 100.2 mg/dL to 95.6 mg/dL (P < .0001). The proportion of patients with poor glycemic control and poor lipid control decreased from 10.3% to 8.42% (P < .0001) and from 38.2% to 32.1% (P < .0001), respectively.
CONCLUSIONS
Sustained interventions directed at the glycemic control of a large population of diabetic patients were associated with significant improvement in their glycemic control and had collateral benefits for indicators of their lipid control. Targeted interventions to improve HgA1c levels may have further benefits in improving other quality measures of diabetic care.
|
pubmed_369_13112
|
pubmed_731_10924
|
Maternal mortality in Africa remains unacceptably high. The prevailing response to reducing maternal mortality has emphasized "reproductive health" and has failed to clearly focus on those causes responsible for 90 percent of maternal deaths. In contrast, the "Safe Passages" model directs training and resources toward interventions that save the lives of mothers and babies. Within the Safe Passages model, a "premise" and an "equation" offer an ethical and strategic framework for maternal health-care development which respects human life and dignity and prioritizes those interventions most likely to reduce maternal and newborn deaths. The Safe Passages "equation" emphasizes the key components of respect for persons, safe birth, and fertility literacy. Successful training and development programs should work to insure participants and organizations are inspired, educated, equipped, and evaluated.
|
10.1179/002436311803888393
|
pubmed_33_16474
|
Despite the discovery of the widely expressed CLCA (chloride channel regulators, calcium-activated) proteins more than 15 years ago, their seemingly diverse functions are still poorly understood. With the recent generation of porcine animal models for cystic fibrosis (CF), members of the porcine CLCA family are becoming of interest as possible modulators of the disease in the pig. Here, we characterize pCLCA2, the porcine ortholog of the human hCLCA2 and the murine mCLCA5, which are the only CLCA members expressed in the skin. Immunohistochemical studies with a specific antibody against pCLCA2 have revealed a highly restricted pCLCA2 protein expression in the skin. The protein is strictly co-localized with filaggrin and trichohyalin in the granular layer of the epidermis and the inner root sheath of the hair follicles, respectively. No differences have been observed between the expression patterns of wild-type pigs and CF transmembrane conductance regulator(-/-) pigs. We speculate that pCLCA2 plays an as yet undefined role in the structural integrity of the skin or, possibly, in specialized functions of the epidermis, including barrier or defense mechanisms.
|
10.1007/s00441-012-1482-9
|
pubmed_826_15133
|
The majority of individuals gamble during their lifetime; however only a subset of these individuals develops problematic gambling. Gray's Reinforcement Sensitivity Theory may be relevant to understanding gambling problems. Differences in sensitivity to punishments and rewards can influence an individual's behavior and may be pertinent to the development of gambling problems. This study examined the functional associations between sensitivity to punishment (SP), sensitivity to reward (SR), and gambling problems in a sample of 2254 college students. Zero-inflated negative binomial regression was used to predict gambling problems as well as the absence of gambling problems. Gambling problems were hypothesized to be positively associated with SR and inversely associated with SP. In addition, SP was hypothesized to moderate the association between SR and gambling problems, attenuating the strength of the association. As hypothesized, SR was positively associated with gambling problems. However, SP did not moderate the relationship between SR and gambling problems. SP did, however, moderate the relationship between SR and the likelihood of never experiencing gambling problems. The results demonstrate that individual differences in SP and SR are functionally associated with gambling problems.
|
pubmed_826_15133
|
pubmed_533_12434
|
Our previous study demonstrated that neutrophils play an important role in host defense against Coxiella burnetii infection in mice. In this study, avirulent strain C. burnetii Nine Mile phase II (NMII) was used to examine if C. burnetii can modulate mouse bone marrow-derived neutrophil apoptosis. The results indicated that NMII can inhibit neutrophil apoptosis. Western blotting demonstrated that caspase-3 cleavage was decreased in NMII-infected neutrophils, while phosphorylated mitogen-activated protein kinase (MAPK) p38 and extracellular signal-regulated kinase 1 (Erk1) were increased. Additionally, p38, Erk1/2, phosphoinositide 3-kinase (PI3K), or NF-κB inhibitors reduced the ability of NMII to inhibit neutrophil apoptosis. These results suggest that NMII-mediated inhibition of neutrophil apoptosis depends on its ability to activate neutrophil MAPK pathways. Antiapoptotic protein myeloid cell leukemia-1 (Mcl-1) was significantly increased in NMII-infected neutrophils, and an Mcl-1 inhibitor significantly reduced the ability of NMII to inhibit neutrophil apoptosis. Mcl-1 protein stability was enhanced by phosphorylation at Thr-163 by Erk, and the protein levels were regulated by p38, Erk, PI3K, and NF-κB. Furthermore, the observation that a type IV secretion system (T4SS)-deficient dotA mutant showed a significantly reduced ability to inhibit neutrophil apoptosis compared to wild-type (WT) NMII suggests that T4SS-secreted factors may be involved in NMII-induced inhibition of neutrophil apoptosis. Collectively, these results demonstrate that NMII inhibits neutrophil apoptosis through inhibition of caspase-3 cleavage and activation of MAPK survival pathways with subsequent expression and stabilization of antiapoptotic protein Mcl-1, a process that may partially require the T4SS.
|
10.1128/IAI.00504-17
|
pubmed_786_21719
|
In vertebrate embryos, neural crest cells migrate extensively to defined sites where they differentiate into a complex array of derivatives, ranging from neurons to pigment cells. Neural crest cells emerge uniformly from the neural tube but their subsequent migratory pattern is segmented along much of the body axis. What factors control this segmental migration? At trunk levels, it is imposed by the intrinsic segmentation of the neighbouring somitic mesoderm, while in the head, intrinsic information within the neural tube as well as extrinsic influences from the ectoderm are involved. A variety of cell-cell and cell-extracellular matrix interactions are thought to influence initiation and movement of neural crest cells. This review summarizes recent progress from both experimental embryology and cell biology approaches in uncovering the mechanisms underlying neural crest cell migration.
|
10.1016/0962-8924(93)90089-j
|
pubmed_851_18503
|
Monolayer and suspension cultures of tumor (BMG-1, CCRF-CEM), normal (AG1522, HADF, lymphocytes) and ATM-mutant (GM4405) human cells were exposed to X-rays at doses used in radiotherapy (high dose and high dose-rate) or radiological imaging (low dose and low dose-rate). Radiation-induced DNA damage, its persistence, and possible bystander effects were evaluated, based on DNA damage markers (γ-H2AX, p53ser15) and cell-cycle-specific cyclins (cyclin B1 and cyclin D1). Dose-dependent DNA damage and a dose-independent bystander response were seen after exposure to high dose and high dose-rate radiation. The level of induced damage (expression of p53ser15, γ-H2AX) depended on ATM status. However, low dose and dose-rate exposures neither increased expression of marker proteins nor induced a bystander response, except in the CCRF-CEM cells. Bystander effects after high-dose irradiation may contribute to stochastic and deterministic effects. Precautions to protect unexposed regions or to inhibit transmission of DNA damage signaling might reduce radiation risks.
|
10.1016/j.mrgentox.2017.06.007
|
pubmed_871_3441
|
This paper presents a kind of single-chip-microcomputer based mid-frequency current physiotherapy instrument. Its composition, function, hardware and software are briefly introduced.
|
pubmed_871_3441
|
pubmed_449_14480
|
The Calcium homeostasis in the perinatal period depends on the changes of the Calcium balance and on the influence of the three Calcium-regulating hormones parathyroid hormone, Calcitonin and 1,25-Dihydroxycholecalciferol. The most common disorder is neonatal hypocalcemia which occurs either as early type (frequent, mainly in prematures) or as late type (rare, probably due to transient hypoparathyroidism).
|
pubmed_449_14480
|
pubmed_773_1088
|
Ten digitalized patients were monitored for detection of cardiac arrhythmias 0 to 8 hr after daily maintenance dose of digoxin in the fasting state. Transient cardiac arrhythmias attributable to digoxin were seen at 2 to 5 hr in 5 subjects. Initial serum concentrations of digoxin were within standard clinical limits in all subjects, but, higher steady-state levels were present in patients with arrhythmias (1.2 to 1.7 ng/ml) than in the others (0.7 to 1.2 ng/ml). The postadministrative serum peak concentrations were also higher in the patients with arrhythmias.
|
10.1002/cpt1976203266
|
pubmed_238_16259
|
BACKGROUND
This study aimed to determine the kinematics of medial pivot total knee arthroplasty by comparing weight-bearing and non-weight-bearing deep knee bending and to evaluate the effect of the weight-bearing state on the kinematics.
METHODS
The kinematics of 19 knees were investigated under fluoroscopy during squatting (weight-bearing) and active-assisted knee bending (non-weight-bearing) using two- to three-dimensional registration technique. Accordingly, range of motion, anteroposterior translation for the medial and lateral low contact points, axial rotation of the femoral component relative to the tibial component and kinematic pathway were evaluated.
FINDINGS
There was no difference in range of motion between the two states. The medial anteroposterior translation showed no significant movement with no anterior translation in both the weight-bearing and non-weight-bearing from 0° to 90° of flexion. Regarding the lateral anteroposterior translation, a posterior translation was observed during weight-bearing, whereas a slight anterior translation from 0° to 30° of flexion and subsequent posterior translation were found in the non-weight-bearing. Femoral external rotation was observed in the weight-bearing, whereas femoral internal rotation was seen from 0° to 30° of flexion and subsequent femoral external rotation was observed in the non-weight-bearing. The kinematic pathway showed medial pivot motion and subsequent bicondylar rollback in the weight-bearing, whereas only medial pivot motion was observed in the non-weight-bearing.
INTERPRETATION
The medial anteroposterior translation of the femur during deep knee bending showed no anterior motion in the two states. The lateral anteroposterior translation and femoral rotation were different in the mid-flexion range between the two states.
|
10.1016/j.clinbiomech.2022.105762
|
pubmed_245_15822
|
Next generation sequencing (NGS) technologies have revolutionized our approach to genomic research. The use of whole genome sequencing (WGS), whole exome sequencing (WES), transcriptome profiling, and targeted DNA sequencing has exponentially improved our understanding of the human genome and the genetic complexities underlying malignancy. Yet, WGS and WES clinical applications remain limited due to high costs and the large volume of data generated. When utilized to address biological questions in basic science studies, targeted sequencing panels have proven extremely valuable due to reduced costs and higher sequencing depth. However, the routine application of targeted sequencing to the clinical setting is limited to a few cancer subtypes. Some highly aggressive tumor types, like type 2 endometrial cancer (EC), could greatly benefit from routine genomic analysis using targeted sequencing. To explore the potential utility of a mid size panel (~150 genes) in the clinical setting, we developed and validated a custom panel against WGS, WES, and another commercially available targeted panel. Our results indicate that a mid size custom designed panel is as efficient as WGS and WES in mapping variants of biological and clinical relevance, rendering higher coverage, at a lower cost, with fewer variants of uncertain significance. Because of the much higher sequencing depth that could be achieved, our results demonstrate that targeted sequencing outperformed WGS and WES in the mapping of pathogenic variants in a breast cancer case, as well as a case of mixed serous and high-grade endometrioid EC, the most aggressive EC subtype.
|
10.18632/oncotarget.22116
|
pubmed_498_20100
|
BACKGROUND
TikTok is one of the most popular and fastest-growing social media apps in the world. Previous studies have analyzed the quality of patient education information on older video platforms, but the quality of plastic and cosmetic surgery videos on TikTok has not yet been determined.
OBJECTIVES
The aim of this study was to analyze the source and quality of certain cosmetic procedure videos on TikTok.
METHODS
The TikTok mobile application was queried for content related to 2 popular face procedures (rhinoplasty and blepharoplasty) and 2 body procedures (breast augmentation and abdominoplasty). Two independent reviewers analyzed video content according to the DISCERN scale, a validated, objective instrument that assesses the quality of information on a scale of 1 to 5. Quality scores were compared between videos produced by medical and nonmedical creators and between different content categories.
RESULTS
The included videos attracted 4.8 billion views and 76.2 million likes. Videos were created by medical doctors (56%) and laypersons (44%). The overall average DISCERN score out of 5 corresponded to very poor video quality for rhinoplasty (1.55), blepharoplasty (1.44), breast augmentation (1.25), and abdominoplasty (1.29). DISCERN scores were significantly higher among videos produced by doctors than by laypersons for all surgeries. Comedy videos consistently had the lowest average DISCERN scores, whereas educational videos had the highest.
CONCLUSIONS
It is increasingly important that medical professionals understand the possibility of patient misinformation in the age of social media. We encourage medical providers to be involved in creating quality information on TikTok and educate patients about misinformation to best support health literacy.
|
10.1093/asj/sjab291
|
pubmed_944_24199
|
Despite acknowledgement that paid caregivers have a significant impact on the lives of people with intellectual disability, the subjective experience of staff gender is rarely considered in research. Qualitative data from a study on the sexual health needs of men and boys with intellectual disability is presented. We designed this study to determine what impact staff gender has on the sexual health needs of men and boys with intellectual disability. Findings suggest that although staff traverse the same geographies of care, they do it in uniquely gendered ways. Staff gender is an important consideration when dealing with sexual health matters and can enhance the type and quality of relationships between people with intellectual disability.
|
10.1352/1934-9556-49.5.341
|
pubmed_354_21049
|
BACKGROUND
The PRogramme for Improving Mental health care (PRIME) designed, implemented and evaluated a comprehensive mental healthcare plan (MHCP) for Sehore district, Madhya Pradesh, India.AimsTo provide quantitative measures of outputs related to implementation processes, describe the role of contextual factors that facilitated and impeded implementation processes, and discuss what has been learned from the MHCP implementation.
METHOD
A convergent parallel mixed-methods design was used. The quantitative strand consisted of process data on mental health indicators whereas the qualitative strand consisted of in-depth interviews and focus group discussions with key stakeholders involved in PRIME implementation.
RESULTS
The implementation of the MHCP in Sehore district in Madhya Pradesh, India, demonstrated that it is feasible to establish structures (for example Mann-Kaksha) and operationalise processes to integrate mental health services in a 'real-world' low-resource primary care setting. The key lessons can be summarised as: (a) clear 'process maps' of clinical interventions and implementation steps are helpful in monitoring/tracking the progress; (b) implementation support from an external team, in addition to training of service providers, is essential to provide clinical supervision and address the implementation barriers; (c) the enabling packages of the MHCP play a crucial role in strengthening the health system and improving the context/settings for implementation; and (d) engagement with key community stakeholders and incentives for community health workers are necessary to deliver services at the community-platform level.
CONCLUSIONS
The PRIME implementation model could be used to scale-up mental health services across India and similar low-resource settings.Declaration of interestNone.
|
10.1192/bjo.2019.53
|
pubmed_989_23592
|
The phased-array radio frequency (RF) coil plays a vital role in magnetic resonance-guided focused ultrasound (MRgFUS) neuromodulation studies, where accurate brain functional stimulations and neural circuit observations are required. Although various designs of phased-array coils have been reported, few are suitable for ultrasound stimulations. In this study, an MRgFUS neuromodulation system comprised of a whole brain coverage non-human primate (NHP) RF coil and an MRI-compatible ultrasound device was developed. When compared to a single loop coil, the NHP coil provided up to a 50% increase in the signal-to-noise ratio (SNR) in the brain and acquired better anatomical image-quality. The NHP coil also demonstrated the ability to achieve higher spatial resolution and reduce distortion in echo-planer imaging (EPI). Ultrasound beam characteristics and transcranial magnetic resonance acoustic radiation force (MR-ARF) were measured for simulated positions, and calculated B0 maps were employed to establish MRI-compatibility. The differences between focused off and on ultrasound techniques were measured using SNR, g-factors, and temporal SNR (tSNR) analyses and all deviations were under 2.3%. The EPI images quality and stable tSNR demonstrated the suitability of the MRgFUS neuromodulation system to conduct functional MRI studies. Last, the time course of the blood oxygen level dependent (BOLD) signal of posterior cingulate cortex in a focused ultrasound neuromodulation study was detected and repeated with MR thermometry.
|
10.1109/TMI.2020.3019087
|
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