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pubmed_515_15825
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Eosinophil cationic protein (ECP/RNase 3) and the skin derived ribonuclease 7 (RNase 7) are members of the RNase A superfamily. RNase 3 is mainly expressed in eosinophils whereas RNase 7 is primarily secreted by keratinocytes. Both proteins present a broad-spectrum antimicrobial activity and their bactericidal mechanism is dependent on their membrane destabilizing capacities. Using phospholipid vesicles as membrane models, we have characterized the protein membrane association process. Confocal microscopy experiments using giant unilamellar vesicles illustrate the morphological changes of the liposome population. By labelling both lipid bilayers and proteins we have monitored the kinetic of the process. The differential protein ability to release the liposome aqueous content was evaluated together with the micellation and aggregation processes. A distinct morphology of the protein/lipid aggregates was visualized by transmission electron microscopy and the proteins overall secondary structure in a lipid microenvironment was assessed by FTIR. Interestingly, for both RNases the membrane interaction events take place in a different behaviour and timing: RNase 3 triggers first the vesicle aggregation, while RNase 7 induces leakage well before the aggregation step. Their distinct mechanism of action at the membrane level may reflect different in vivo antipathogen functions.
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10.1016/j.bbamem.2009.01.013
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pubmed_700_10155
|
The present study was designed to analyze the usefulness of plain radiographs in evaluating bone healing. Rabbit tibiae were osteotomized, externally fixed, and allowed to heal for 3-8 weeks. Bones were harvested, x-rayed, and tested to failure in a dynamic torsion tester. AP and lateral radiographs of 10 rabbit tibia pairs and 10 individual rabbit tibiae were selected randomly for use in a questionnaire, given to 93 physicians who routinely assess fracture healing to evaluate clinicians' ability to assess bone strength. The results indicated that clinicians can differentiate the relative strength of bones by comparing two sets of radiographs. However, the strength determination from a single set of radiographs of a fracture is unreliable, the tendency being to evaluate the fracture to be weaker than it actually is.
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10.1097/00005131-198903010-00006
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pubmed_749_17393
|
Tungsten oxide (WOx) has been widely studied for versatile applications based on its photocatalytic, intrinsic catalytic, and electrocatalytic properties. Among the several nanostructures, we focused on the flower-like structures to increase the catalytic efficiency on the interface with both increased substrate interaction capacities due to their large surface area and efficient electron transportation. Therefore, improved WOx nanoflowers (WONFs) with large surface areas were developed through a simple hydrothermal method using sodium tungstate and hydrogen chloride solution at low temperature, without any additional surfactant, capping agent, or reducing agent. Structural determination and electrochemical analyses revealed that the WONFs have hexagonal Na0.17WO3.085·0.17H2O structure and exhibit peroxidase-like activity, turning from colorless to blue by catalyzing the oxidation of a peroxidase substrate, such as 3,3',5,5'-tetramethylbenzidine, in the presence of H2O2. Additionally, a WONF-modified glassy carbon electrode was adopted to monitor the electrocatalytic reduction of H2O2. To verify the catalytic efficiency enhancement by the unique shape and structure of the WONFs, they were compared with calcinated WONFs, cesium WOx nanoparticles, and other peroxidase-like nanomaterials. The results indicated that the WONFs showed a low Michaelis-Menten constant (km), high maximal reaction velocity (vmax), and large surface area.
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10.1038/srep40928
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pubmed_872_13399
|
The aim of the present study was to evaluate the clinical outcome following application of an enamel matrix derivative in degree II mandibular furcation involvements. Ten patients with chronic periodontitis, presenting a total of eight buccal and eight lingual degree II furcation involvements, were included in the study. The following clinical parameters were evaluated prior to treatment and after 6, 12, and 36 months: probing attachment level in horizontal direction in the buccal and/or lingual furcation area (PAL-H) and probing attachment level in vertical direction (PAL-V) at the center of the buccal/lingual furcation area. The postoperative healing phase was uneventful in all cases, and no complications were observed throughout the entire study period. At 6 months, the mean PAL-H of the buccal defects was reduced from 4.0 +/- 1.3 mm to 2.6 +/- 1.4 mm, and the mean PAL-V was reduced from 5.2 +/- 2.0 mm to 4.0 +/- 1.6 mm. At the lingual defects, the mean PAL-H was reduced from 3.6 +/- 1.3 mm to 3.1 +/- 1.1 mm, and the mean PAL-V was reduced from 5.6 +/- 2.0 mm to 4.3 +/- 1.8 mm. At 12 and 36 months, clinical parameters remained similar, without any further clinical improvement. These results suggest that the treatment of degree II mandibular furcation involvements with enamel matrix derivative might lead to clinical improvement. However, controlled clinical trials and histologic studies are needed to examine the clinical significance of these results and the characteristics of healing following application of enamel matrix derivative.
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pubmed_872_13399
|
pubmed_579_25512
|
Rituximab, a monoclonal antibody (MAb) against CD20, was the first MAb approved by the US Food and Drug Administration (FDA) for treatment of B cell non-Hodgkin lymphoma (B-NHL). Conjugating toxins to MAb was a technical challenge; however, with improvements in linker technology, immunoconjugates were constructed and revolutionized cancer treatment. Gemtuzumab ozogamicin was the first antibody drug conjugate (ADC) approved by the FDA. Because of the success of brentuximab vedotin and ado-trastuzumab emtansine in treating Hodgkin lymphoma (HL) and HER2-positive breast cancer, respectively, newer ADCs are being investigated. Brentuximab vedotin is approved for both HL and anaplastic large cell lymphoma. Newer ADCs, such as polatuzumab vedotin (targeting CD79b), pinatuzumab vedotin (targeting CD22), inotuzumab ozogamicin (targeting CD19), SAR3419 (targeting CD19), IMGN529 (targeting CD37), and SGN-CD19A (targeting CD19), have shown promising preclinical and early clinical activity. These findings will change the landscape of B-NHL treatment away from age-old "CHOP"-based chemotherapies.
|
10.1007/s11912-015-0466-9
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pubmed_655_10908
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HIV infection is the new "great mimic." Although its more common signs and symptoms are well known, HIV infection sometimes presents with rheumatologic manifestations, as does human T-cell lymphotrophic virus type I (HTLV-I), the causative agent of adult T-cell leukemia. This review briefly describes these manifestations and presents a logical clinical approach to their diagnosis and treatment.
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10.3949/ccjm.65.8.436
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pubmed_660_3177
|
BACKGROUND
There exist several computational tools which allow for the optimisation and inference of biological networks using a Boolean formalism. Nevertheless, the results from such tools yield only limited quantitative insights into the complexity of biological systems because of the inherited qualitative nature of Boolean networks.
RESULTS
We introduce optPBN, a Matlab-based toolbox for the optimisation of probabilistic Boolean networks (PBN) which operates under the framework of the BN/PBN toolbox. optPBN offers an easy generation of probabilistic Boolean networks from rule-based Boolean model specification and it allows for flexible measurement data integration from multiple experiments. Subsequently, optPBN generates integrated optimisation problems which can be solved by various optimisers. In term of functionalities, optPBN allows for the construction of a probabilistic Boolean network from a given set of potential constitutive Boolean networks by optimising the selection probabilities for these networks so that the resulting PBN fits experimental data. Furthermore, the optPBN pipeline can also be operated on large-scale computational platforms to solve complex optimisation problems. Apart from exemplary case studies which we correctly inferred the original network, we also successfully applied optPBN to study a large-scale Boolean model of apoptosis where it allows identifying the inverse correlation between UVB irradiation, NFκB and Caspase 3 activations, and apoptosis in primary hepatocytes quantitatively. Also, the results from optPBN help elucidating the relevancy of crosstalk interactions in the apoptotic network.
SUMMARY
The optPBN toolbox provides a simple yet comprehensive pipeline for integrated optimisation problem generation in the PBN formalism that can readily be solved by various optimisers on local or grid-based computational platforms. optPBN can be further applied to various biological studies such as the inference of gene regulatory networks or the identification of the interaction's relevancy in signal transduction networks.
|
10.1371/journal.pone.0098001
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pubmed_460_10912
|
The vast majority of chiral compounds crystallize into racemic crystals. It has been predicted and was experimentally established as a rule that chiral molecules on surfaces are more easily separated into homochiral domains due to confinement into a plane and lower entropic contributions. We investigated the formation and stability of two-dimensional tartrate crystals on a Cu(110) surface for the racemic mixture for the first time by means of temperature-programmed desorption (TPD), low-energy electron diffraction (LEED), and X-ray photoelectron spectroscopy (XPS). At low coverage, a bitartrate species becomes separated into homochiral domains, while at high coverage a monotartrate species forms a racemic mixture. At the same coverage and lateral arrangement, the thermally induced autocatalytic decomposition reaction occurs for the monotartrate racemate at a lower temperature than for the pure enantiomers. The stereochemistry in this so-called "surface explosion" reaction is explained by a higher stability of the enantiopure lattice due to lateral hydrogen-bond formation. The higher stability of the enantiopure two-dimensional lattice is in contrast to the higher stability of racemic three-dimensional tartaric acid crystals but is consistent with the observation that homochirality is preferred in hydrogen-bonded self-assembled biomolecular structures.
|
10.1021/ja048206d
|
pubmed_827_23225
|
While the abuse potential of cocaine stems mainly from its ability to increase dopaminergic transmission in limbic regions, drug actions on other monoamine-innervated circuits may contribute to the development and maintenance of cocaine addiction. Previous extracellular recordings in anaesthetized rats revealed a facilitatory influence of cocaine on primary sensory pathways, which could influence the processing of drug-related stimuli during the development of cocaine addiction. We further analysed these sensory effects of cocaine in freely behaving rats (n = 9). Using an array of eight microelectrodes chronically implanted in infragranular layers of primary somatosensory cortex, we recorded the basal activity of 40 single- and 64 multiunits and their response to electrical stimulation of the whisker pad before and after incremental doses of cocaine (0.25-2 mg/kg i.v.). Both spontaneous and cocaine-induced explorations were associated with elevated basal firing of the cortical neurons and suppression of their short-latency excitation and postexcitatory inhibition in response to the whisker-pad stimulation. In addition to exploration-related alterations, the administration of cocaine enhanced the long-latency rebound excitation induced by the whisker-pad stimulation. This component of the sensory response, which is more labile and does not seem to convey information about the physical characteristics of the stimulus, may participate in the processing of drug-related sensory stimuli.
|
10.1111/j.0953-816x.2004.03186.x
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pubmed_241_8434
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Subcutaneous human IgG (SCIG) therapy in primary immunodeficiency (PID) offers sustained IgG levels throughout the dosing cycle and fewer adverse events (AEs) compared to intravenous immunoglobulin (IVIG). A phase I study showed good local tolerability of IgPro20, a new 20% liquid SCIG stabilized with L-proline. A prospective, open-label, multicenter, single-arm, phase III study evaluated the efficacy and safety of IgPro20 in patients with PID over 15 months. Forty-nine patients (5-72 years) previously treated with IVIG received weekly subcutaneous infusions of IgPro20. The mean serum IgG level was 12.5 g/L. No serious bacterial infections were reported. There were 96 nonserious infections (rate 2.76/patient per year). The rate of days missed from work/school was 2.06/patient per year, and the rate of hospitalization was 0.2/patient per year. Ninety-nine percent of AEs were mild or moderate. No serious, IgPro20-related AEs were reported. IgPro20 effectively protected patients with PID against infections and maintained serum IgG levels without causing unexpected AEs.
|
10.1007/s10875-010-9423-4
|
pubmed_570_13622
|
Functional tricuspid regurgitation (TR) primarily arises from asymmetric dilation of the tricuspid annulus in the setting of right ventricular dysfunction and enlargement in response to left-sided myocardial and valvular abnormalities. Even if TR is not severe at the time of mitral valve surgery, TR can worsen and even appear late after successful mitral valve surgery, which portends a poor prognosis. Despite data demonstrating inferior outcomes in the presence of residual TR, surgical repair for functional TR remains underused. However, "benign neglect" of TR, especially in the presence of tricuspid annular dilation, is unacceptable. Surgical repair should consist of placement of a rigid or semirigid annular ring, which has been shown to provide superior durability compared with suture and flexible band-based therapies. Finally, minimally invasive and percutaneous approaches for correcting functional TR may increase the delivery of therapy and allow treatment of patients with recurrent TR at high risk for reoperation.
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10.1053/j.semtcvs.2010.05.001
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pubmed_270_13216
|
Tight control of blood glucose levels and risk factors for cardiovascular disease (e.g., hypertension, hypercholesterolemia) can substantially reduce the incidence of microvascular and macrovascular complications from type 1 diabetes. Physicians play an important role in helping patients make essential lifestyle changes to reduce the risk of these complications. Key recommendations that family physicians can give patients to optimize their outcomes include: take control of daily decisions regarding your health, focus on preventing and controlling risk factors for cardiovascular disease, tightly control your blood glucose level, be cognizant of potentially inaccurate blood glucose test results, use physiologic insulin replacement regimens, and learn how to manage and prevent hypoglycemia.
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pubmed_270_13216
|
pubmed_499_16779
|
Carcinoid tumors referred to neuroendocrine neoplasms that often are indolent and may not became clinical apparent until there has been metastatic spread. Urinary 5-hydroxyindoleacetic acid (5-HIAA) was recommended as a first-line screening biomarker for the diagnosis and follow-up of carcinoid tumors. The measurement of this analyte is conventionally performed by spectrophotometer or high performance liquid chromatography, and has switched to liquid chromatography-tandem mass spectrometry (LC-MS/MS) recently. In this study, a fast, simple and reliable LC-MS/MS method has been developed and validated for 24 h urinary 5-HIAA determination and the quality assurance referring to post-implementation monitoring has been explored. 50 μL of urine was mixed with 200 μL of a 50% methanol/water solution containing the internal standard 5-HIAA-d5. The mixture was centrifuged and the supernatant was used for direct analysis by LC-MS/MS. The retention time of 5-HIAA is 2.37 min and a total run time is 4 min. This method was validated for excellent linearity from 0.675 to 43.3 μM with CVs ≤ 6.64% and good recovery in the range of 87.1%-107%. No obvious matrix effect was observed. Intra- and inter-day imprecision were below 3.95% and 4.66% respectively. The reference interval of 24-hour urinary 5-HIAA in Chinese adults was established. The quality assurance could ensure reliable and comparable results in routine clinical testing. Thus, this fast, simple and reliable LC-MS/MS method could be proposed as a tool for clinical testing of urinary 5-HIAA in quality-controlled environments.
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10.1016/j.jchromb.2022.123315
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pubmed_995_9155
|
The clinical features of 33 patients with primary intracranial arachnoid cysts are reviewed. Magnetic resonance imaging was performed in 9 patients and was particularly useful in the multiplanar definition of complex cysts and in differentiating arachnoid cysts from other lesions that are hypodense on computed tomographic scans. Hydrocephalus, cranial nerve palsies, or symptomatic brain compression was considered an indication for surgical intervention in 21 patients. Outcome was uniformly good: mild focal weakness and seizure disorders constituted the sequelae.
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10.1002/ana.410210405
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pubmed_506_12300
|
Nrf2, a central regulator of the cellular defense against oxidative stress and inflammation, participates in modulating hepatocyte proliferation during liver regeneration. It is not clear, however, whether Nrf2 regulates hepatocyte growth, an important cellular mechanism to regain the lost liver mass after partial hepatectomy (PH). To determine this, various analyses were performed in wild-type and Nrf2-null mice following PH. We found that, at 60 h post-PH, the vast majority of hepatocytes lacking Nrf2 reduced their sizes, activated hepatic progenitor markers (CD133, TWEAK receptor, and trefoil factor family 3), depleted HNF4α protein, and downregulated the expression of a group of genes critical for their functions. Thus, the identity of hepatocytes deficient in Nrf2 was transiently but massively impaired in response to liver mass loss. This event was associated with the coupling of protein depletion of hepatic HNF4α, a master regulator of hepatocyte differentiation, and concomitant inactivation of hepatic Akt1 and p70S6K, critical hepatocyte growth signaling molecules. We conclude that Nrf2 participates in maintaining newly regenerated hepatocytes in a fully differentiated state by ensuring proper regulation of HNF4α, Akt1, and p70S6K during liver regeneration.
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10.1371/journal.pone.0107423
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pubmed_650_13150
|
Integrin (beta 2 subunit of the LEU-CAM family, CD18) expression on peripheral blood and urinary granulocytes was studied in renal allograft recipients. Circulating granulocyte CD18 expression was normal except for patients with CMV infection. In contrast, the majority of patients with urinary tract infection had low numbers of CD18+ cells collected from urine, and the same abnormality could also be observed in approx. 50% of non-infected recipients. These disturbances were associated with transplantation, as no such deficits were seen in the infected non-transplant patients or patients with glomerular diseases on immunosuppression. Short culture of granulocytes with immunosuppressants did not diminish integrin expression. Deficient granulocyte integrin expression, especially in urinary tract, may be associated with increased susceptibility to infection in renal transplant recipients, although immunosuppression alone could not be incriminated as a sole factor responsible for this deficit.
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pubmed_650_13150
|
pubmed_992_1905
|
Creutzfeldt-Jakob disease (CJD) has a significant degree of clinical heterogeneity that is especially found in the features at onset. Here we present a patient with the sporadic form of CJD mimicking Wernicke encephalopathy. We first treated him with a high dose of thiamine; however, the vitamin B1 levels proved to be normal, which ruled out Wernicke encephalopathy. Meanwhile, his clinical condition progressively worsened and he developed a rapidly progressive cognitive disorder, mutism and myoclonus of the muscles. At this point, the diagnosis of CJD was most likely. The patient died two months after the first symptoms. Autopsy showed prion-protein depositions in several regions. Genetic analysis was negative for familial CJD. Those findings confirmed the diagnosis of 'sporadic Creutzfeldt-Jakob disease'. CJD presents in a wide range of sequences and clinical symptoms. Therefore, recognition in the early stage can be difficult.
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pubmed_992_1905
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pubmed_385_10679
|
BACKGROUND
Preimplantation genetic diagnosis (PGD) is a technique which is often related to emotional debates because of its ethical and social implications. Worldwide there are different forms of legislation; Germany constitutes an interesting case because of the historical background concerning eugenics and dealing with handicapped persons at the time of national socialism. PGD is currently not legal but there are still polarized positions and legalization remains an issue. Studies about the attitudes of the general population towards PGD are rare.
METHODS
Data were collected in a representative survey carried out in November 2003. Subjects were 2110 persons in Germany aged 18-50 years.
RESULTS AND CONCLUSIONS
Respondents had little knowledge about PGD. There were incorrect assumptions about the diagnostic possibilities and a lack of basic genetic knowledge. A tendency towards a general acceptance of PGD for medical indications was found. Non-medical indications such as sex selection were generally not accepted. It could be observed that respondents who already had a notion about PGD overestimated the diagnostic possibilities and would eventually use PGD in the future more than respondents who had never heard about PGD before.
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10.1093/humrep/deh548
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pubmed_324_17104
|
β-Amyloid (Aβ) may play an important role in the pathogenesis of Alzheimer's disease. However, a causal relationship between Aβ oligomers and layer-specific neurodegeneration has not been clarified. Here we show up-regulation of calsyntenin (Cst)-3 in cultured neurons treated with Aβ oligomers and in Tg2576 mice. Cst-3 is distributed in large neurons in layers 2-3 and 5 of the cerebral cortex, and accumulated in dystrophic neurites surrounding Aβ-plaques. Overexpression of Cst-3 accelerates neuronal death. These results indicate that up-regulation of Cst-3 in cortical neurons in layers 2-3 and 5 by Aβ oligomers may lead to increase in vulnerability of neurons.
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10.1016/j.febslet.2011.01.025
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pubmed_731_18111
|
Withanolides are C-28 ergostane steroids known to demonstrate some very interesting therapeutic properties. Numerous withanolides have been isolated from a variety of different plant species and can be employed to treat various types of cancers. Withanolides are indeed capable of demonstrating excellent anticancer, anti-inflammatory, and neuroprotective activities. Additionally, libraries of prepared withaferin A analogs incorporating an acyl, sulphate, amide and aldehyde functionality have demonstrated the most potential response. It is of particular interest to note that an acetyl group at either C-4, C-19 or C-27 enhances the anticancer effects. Since the majority of natural withanolides reported in patents are classified as "Type-A", it is our opinion that there should now be a focus on developing "Type-B" withanolides and an investigation into their various therapeutic applications. Moreover, very little real innovation in synthetic methodologies has been reported which opens up huge possibilities for novel synthetic methodologies to be developed for the production of larger libraries new withanolides and their analogs to incorporate chemical diversity. In addition, since withanolides have the capability to conjugate with other anticancer compounds, this should encourage scientists to prepare lead compounds in cancer drug discovery.
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10.2174/1574892813666180808154928
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pubmed_946_9642
|
The results of a study conducted on individuals exposed to aeronautical environment noise (flight personnel, runway operators, mechanics etc.) are reported. A particular suprathreshold automatic audiometric technique, called P.A.T. (automatic Peyser test) was used because there was evidence that it was more trustworthy than other suprathreshold tests and because this test permits a graphic follow-up of the dynamic evolution of "uditive fatique" phenomenon. The conclusion is drawn with this method it is possible to evaluate more precisely both the entity of the damage and on possible suffering of Corti's organ in individuals exposed to noise, and the simplicity of the test is underlined. Moreover the test is advantageous because it can be done using the normal routine diagnostic apparatus.
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pubmed_946_9642
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pubmed_421_21699
|
Sensitive detection of low-abundance driver mutations may provide valuable information for precise clinical treatment. Compared to next-generation sequencing and droplet digital PCR methods, fluorescent probes show great flexibility in rapid detection of specific mutations with high sensitivity and easily accessible instruments. However, existing approaches with fluorescent probes need an additional step to convert duplex DNA to single-stranded DNA (ssDNA) before the detection step, which increases the time, cost, and risk of loss of low-input target strands. In this work, we attempt to integrate the ssDNA-generation step with the subsequent detection into a programable one-pot reaction by employing lambda exonuclease (λ exo), a versatile nanopore nuclease which exercises different functions on different substrates. The capability of λ exo in discrimination of mismatched bases in 5'- FAM-ended 2 nt-unpaired DNA duplexes was first demonstrated. Specific fluorescent probes were developed for EGFR exon 19 E746-A750del and PIK3CA E545K mutations with discrimination factors as high as 8470 and 884, respectively. By mixing the probes and λ exo with the PCR products of cell-free circulating DNA extracted from plasma samples, the reaction was immediately initiated, which allowed sensitive detection of the two types of mutations at an abundance as low as 0.01% within less than 2 h. Compared to existing approaches, the new method has distinct advantages in simplicity, low cost, and rapidity. It provides a convenient tool for companion diagnostic tests and other routine analysis targeting genetic mutations in clinical samples.
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10.1021/acs.analchem.1c00564
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pubmed_121_18219
|
Psychological resilience refers to the ability to cope with adversities, and deficits in resilience might lead to mental illness. The COVID-19 pandemic has had impact on psychological resilience for older adults, but there are as yet no data on its impacts on the mental health of older adults who were living with mild cognitive impairment (MCI). Therefore, the aim of this study was to investigate the impact of the COVID-19 pandemic on psychological resilience in older adults with MCI and to explore associated physical and psychosocial factors. In this cross-sectional study of 268 older adults aged 65-85, we defined MCI as age- and education-adjusted cognitive decline with a standard deviation of 1.0 or more from the reference threshold. During December 2020 to April 2021, we carried out to all participants the 10-item version of the Connor-Davidson Resilience Scale (CD-RISC-10) to measure psychological resilience. We also conducted a comprehensive geriatric assessment including sleep quality and depressive symptoms (Pittsburgh Sleep Quality Index and 15-item Geriatric Depression Scale, respectively). To identify factors associated with CD-RISC-10 scores (mean: 23.3 ± 0.4), multiple regression analysis revealed that older age [coefficient = 0.23, 95% confidence interval (CI) = 0.06-0.39] was significantly correlated with higher scores, whereas poor sleep quality (coefficient = -2.06, 95% CI = -3.93 to -0.19) and depressive symptoms (coefficient = -2.95, 95% CI = -5.70 to -0.21) were significantly correlated with lower scores. In this study, older adults with MCI showed low psychological resilience during the COVID-19 pandemic, and people with low psychological resilience indicated poor sleep quality and depressive symptoms. Our findings suggest directions for devising interventions to maintain mental health and psychological resilience among the vulnerable population of older adults with MCI living under the socially isolated conditions of COVID-19 pandemic restrictions. Our recommendation includes continuous assessment of this population and appropriate care for poor sleep quality and depressive symptoms.
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10.3389/fpsyt.2022.898990
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pubmed_476_13167
|
BACKGROUND
Post-traumatic stress disorder (PTSD) is a severe and debilitating condition. Several pharmacological interventions have been proposed with the aim to prevent or mitigate it. These interventions should balance efficacy and tolerability, given that not all individuals exposed to a traumatic event will develop PTSD. There are different possible approaches to preventing PTSD; universal prevention is aimed at individuals at risk of developing PTSD on the basis of having been exposed to a traumatic event, irrespective of whether they are showing signs of psychological difficulties.
OBJECTIVES
To assess the efficacy and acceptability of pharmacological interventions for universal prevention of PTSD in adults exposed to a traumatic event.
SEARCH METHODS
We searched the Cochrane Common Mental Disorders Controlled Trial Register (CCMDCTR), CENTRAL, MEDLINE, Embase, two other databases and two trials registers (November 2020). We checked the reference lists of all included studies and relevant systematic reviews. The search was last updated on 13 November 2020.
SELECTION CRITERIA
We included randomised clinical trials on adults exposed to any kind of traumatic event. We considered comparisons of any medication with placebo or with another medication. We excluded trials that investigated medications as an augmentation to psychotherapy.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures. In a random-effects model, we analysed dichotomous data as risk ratios (RR) and number needed to treat for an additional beneficial/harmful outcome (NNTB/NNTH). We analysed continuous data as mean differences (MD) or standardised mean differences (SMD).
MAIN RESULTS
We included 13 studies which considered eight interventions (hydrocortisone, propranolol, dexamethasone, omega-3 fatty acids, gabapentin, paroxetine, PulmoCare enteral formula, Oxepa enteral formula and 5-hydroxytryptophan) and involved 2023 participants, with a single trial contributing 1244 participants. Eight studies enrolled participants from emergency departments or trauma centres or similar settings. Participants were exposed to a range of both intentional and unintentional traumatic events. Five studies considered participants in the context of intensive care units with traumatic events consisting of severe physical illness. Our concerns about risk of bias in the included studies were mostly due to high attrition and possible selective reporting. We could meta-analyse data for two comparisons: hydrocortisone versus placebo, but limited to secondary outcomes; and propranolol versus placebo. No study compared hydrocortisone to placebo at the primary endpoint of three months after the traumatic event. The evidence on whether propranolol was more effective in reducing the severity of PTSD symptoms compared to placebo at three months after the traumatic event is inconclusive, because of serious risk of bias amongst the included studies, serious inconsistency amongst the studies' results, and very serious imprecision of the estimate of effect (SMD -0.51, 95% confidence interval (CI) -1.61 to 0.59; I2 = 83%; 3 studies, 86 participants; very low-certainty evidence). No study provided data on dropout rates due to side effects at three months post-traumatic event. The evidence on whether propranolol was more effective than placebo in reducing the probability of experiencing PTSD at three months after the traumatic event is inconclusive, because of serious risk of bias amongst the included studies, and very serious imprecision of the estimate of effect (RR 0.77, 95% CI 0.31 to 1.92; 3 studies, 88 participants; very low-certainty evidence). No study assessed functional disability or quality of life. Only one study compared gabapentin to placebo at the primary endpoint of three months after the traumatic event, with inconclusive evidence in terms of both PTSD severity and probability of experiencing PTSD, because of imprecision of the effect estimate, serious risk of bias and serious imprecision (very low-certainty evidence). We found no data on dropout rates due to side effects, functional disability or quality of life. For the remaining comparisons, the available data are inconclusive or missing in terms of PTSD severity reduction and dropout rates due to adverse events. No study assessed functional disability.
AUTHORS' CONCLUSIONS
This review provides uncertain evidence only regarding the use of hydrocortisone, propranolol, dexamethasone, omega-3 fatty acids, gabapentin, paroxetine, PulmoCare formula, Oxepa formula, or 5-hydroxytryptophan as universal PTSD prevention strategies. Future research might benefit from larger samples, better reporting of side effects and inclusion of quality of life and functioning measures.
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10.1002/14651858.CD013443.pub2
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pubmed_807_11316
|
Deficiency of 5,10-methylenetetrahydrofolate reductase (MTHFR), the very rare methionine synthase reductase (CblE) and methionine synthase (CblG) defects, and the recently identified CblD-variant-1 defect are primary remethylation defects characterized by an isolated defect in methionine synthesis without methylmalonic aciduria. The clinical signs are mainly neurological, and hematological signs are seen in CblE, CblG, and CblD-variant-1 defects. Patients with neonatal or early-onset disease exhibit acute neurological distress. Infants and children have unspecific mental retardation, often with acquired microcephaly. Without appropriate therapy, they may experience acute or rapidly progressive neurological deterioration, which may be fatal. Adolescents and adults show normal development or mild developmental delay initially and then experience rapid neurological or behavioral deterioration. A few patients may have signs of subacute combined degeneration of the spinal cord. Adults may be asymptomatic or present with isolated thromboembolism. All patients with suspected remethylation disorders should receive emergency treatment with parenteral administration of hydroxocobalamin and folate supplements combined with betaine orally. The long-term treatment of CblE, CblG, and CblD-variant-1 defects consists of parenterally administered hydroxocobalamin and orally administered folate and betaine supplements, whereas patients with MTHFR deficiency require long-term oral folate and betaine supplements. Long-term oral methionine therapy should also be considered. Early treatment may lead to a favorable outcome with developmental recovery and prevention of further neurological deterioration. In contrast, most late-treated patients have severe and irreversible neuromotor impairments. Hematological abnormalities are easily corrected.
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10.1007/s10545-010-9120-8
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pubmed_1022_5937
|
The roots of Angelica sinensis (RAS), are a Chinese herbal medicine traditionally used in prescriptions for replenishing blood, treating abnormal menstruation, and other women's diseases. It has also been widely marketed as health food for women's care in Asia, and as a dietary supplement in Europe and America. RAS is well-known for its hematopoietic, antioxidant, and immunoregulatory activities. RAS also possesses anti-cancer, memory, radioprotective, and neuroprotective effects. Phytochemical investigations on this plant led to organic acids, phthalides, polysaccharides, and other metabolites. Based on recent animal studies and clinical trials, RAS has been used in the treatment of gynecologic diseases, cardio-cerebrovascular disease, nervous system diseases, and nephrotic syndrome. In this review, the recent phytochemical and pharmacological studies, drug-drug interactions, clinical applications, and toxicity of RAS are summarized.
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pubmed_1022_5937
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pubmed_332_9274
|
In population-based studies, the prevalence of neurodevelopmental disability is consistently higher in twins than singletons. This is largely because birth weight and gestational age (GA) distributions of twin births are shifted to the left when compared with singleton births, and lower birth weight and lower GA are associated with increased risk of neurodevelopmental disability. From a pathophysiologic perspective, a question of interest is whether neurodevelopmental outcomes of twins differ from singletons after controlling for covariates. If significant differences in outcomes persist, this would suggest that the twining process itself or something intrinsic to shared life in the womb may be responsible for observed differences. From a clinical perspective, when counseling parents at risk for preterm delivery of twins, it is useful to understand how twin outcomes compare relative to singleton outcomes at the same birth weight or GA. The purpose of this review is to examine the long-term neurodevelopmental outcomes of twins compared with singletons with control for important covariates.
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10.1053/j.semperi.2012.02.005
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pubmed_902_1090
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Lantibiotics are biologically active peptides produced by several strains from the phyla Firmicutes and Actinobacteria. They are ribosomally synthesized and undergo posttranslational modifications that endow them with the characteristic (methyl)-lanthionine residues. As a result, lantibiotics contain a variable number of rings, each carrying one thioether link. Many lantibiotics inhibit growth of Gram-positive bacterial strains by interfering with peptidoglycan formation. Because they bind to the key intermediate lipid II at a site not affected by clinically used antibiotics, they are effective against multidrug-resistant strains. We describe a bioassay-based method suitable for finding antibacterial lantibiotics from actinomycete strains and provide selected procedures for characterizing newly discovered lantibiotics for their antibacterial properties.
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10.1007/978-1-60761-594-1_3
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pubmed_422_19835
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This paper describes a Microsoft Word 97 macro designed for restriction endonuclease analysis. Selected DNA fragments in the active Word document can be analyzed through a dynamic dialog box that formats the enzyme restriction lists for further analysis. The results can be obtained in a new Word document with the name of the enzymes, number of cuts and positions. This macro has several advantages: the results can be printed in a format suitable for record keeping, no additional programs are required and it is simple to use.
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10.2144/99276bc05
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pubmed_1053_9105
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Arterial CO2 partial pressure (PaCO2) can be continuously and noninvasively estimated by monitoring end-tidal CO2 partial pressure (PetCO2). However, the difference between the two (P(a-et)CO2) may vary considerably between patients. In 26 patients undergoing general anesthesia for various surgical procedures, P(a-et)CO2 was measured. We tested the hypothesis that certain clinical characteristics are associated with higher P(a-et)CO2 values in a given patient. In addition, we tested the hypothesis that P(a-et)CO2 remains constant during anesthesia by comparing the mean of eight P(a-et)CO2 values, which were measured at 15-min intervals, with the initial (P(a-et)CO2 value. Impaired lung function, defined as a lung score above 6, age above 50 years, and overweight (defined as greater than 120% of ideal body weight) were associated with increased P(a-et)CO2 (mean +/- SD: 6.27 +/- 1.85; 5.27 +/- 2.11; and 6.19 +/- 1.95 mmHg respectively) when compared to normal lung function (lung score less than or equal to 6), age below 50 years, and normal weight (less than 120% of ideal body weight, 3.87 +/- 2.31; 3.55 +/- 2.58; and 3.77 +/- 2.25 respectively). Although these differences are statistically significant, the standard deviations are large and do not allow the prediction of P(a-et)CO2 in a given patient. Initial P(a-et)CO2 correlated well with subsequent P(a-et)CO2 (R = 0.91, P less than 0.001). The mean difference of the subsequent P(a-et)CO2 values from the initial values was 0.05 +/- 0.80 mmHg (mean +/- SD) and was not significantly different from zero. In the patient population studied, P(a-et)CO2 thus remained generally constant during anesthesia.
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pubmed_1053_9105
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pubmed_257_4397
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DNA fragments encoding the mouse steroid 21-hydroxylase (C21 or Cyp21A1) gene are de novo methylated when introduced into the mouse adrenocortical tumor cell line Y1 by DNA-mediated gene transfer. Although CCGG sequences within the C21 gene are de novo methylated, CCGG sites within flanking vector sequences, other mammalian gene sequences driven by the C21 promoter, and the neomycin-resistance gene, which was cotransfected with the C21 gene, do not become methylated. At least two separate signals for de novo methylation are encoded within the gene since three fragments derived from the C21 gene were methylated de novo. Specific de novo methylation of C21-derived sequences does not occur in L cells or Y1 kin8 cells; this suggests that the cellular factors needed for de novo methylation of the C21 gene are not ubiquitous. Most DNA sequences are not de novo methylated when introduced into somatic cells and DNA sequences other than the C21 gene are not de novo methylated when introduced into Y1 cells. Several groups have suggested that de novo methylation occurs in early embryonic cells and that somatic cells strictly maintain their methylation pattern by a semiconservative methyltransferase. Our results suggest that de novo methylation of specific nucleotide sequences can occur in some mammalian somatic cells.
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10.1073/pnas.86.18.6853
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pubmed_832_20105
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Obtaining a purified male sperm specimen from the original forensic sample mixtures is a critical procedure in identifying the criminal suspect in the forensic analysis of sexual assault crimes. Differential extraction (DE) has been used as the gold standard for extracting DNA preferentially from sexual assault samples, however it is laborious, time-consuming and inefficient. In this report a continuous flow two-step acoustic cell separation scheme is proposed for the removal of cell debris and cell-free genomic contaminants, followed by separation of sperm cells from epithelial cells. Based on the above method, a portable forensic sperm cell purification instrument has been constructed for on-site pretreatment of forensic samples in sexual assault crimes, where removal of contaminants and isolation of sperm cells could be automatically performed without the use of cell lysis buffer.
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10.1039/d0lc01198c
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pubmed_482_18262
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The temperature and strain rate significantly affect the ballistic performance of UHMWPE, but the deformation of UHMWPE under thermo-mechanical coupling has been rarely studied. To investigate the influences of the temperature and the strain rate on the mechanical properties of UHMWPE, a Split Hopkinson Pressure Bar (SHPB) apparatus was used to conduct uniaxial compression experiments on UHMWPE. The stress-strain curves of UHMWPE were obtained at temperatures of 20-100 °C and strain rates of 1300-4300 s-1. Based on the experimental results, the UHMWPE belongs to viscoelastic-plastic material, and a hardening effect occurs once UHMWPE enters the plastic zone. By comparing the stress-strain curves at different temperatures and strain rates, it was found that UHMWPE exhibits strain rate strengthening and temperature softening effects. By modifying the Sherwood-Frost model, a constitutive model was established to describe the dynamic mechanical properties of UHMWPE at different temperatures. The results calculated using the constitutive model were in good agreement with the experimental data. This study provides a reference for the design of UHMWPE as a ballistic-resistant material.
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10.3390/polym12071561
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pubmed_58_20922
|
Background
Clinical trial endpoints for Crohn's disease (CD) activity correlate poorly with mucosal inflammation; to assess treatment efficacy, patient-reported outcomes and endoscopic assessments are preferred. This study assessed the impact on treatment efficacy estimations of using different definitions of clinical and endoscopic remission and endoscopic response, and of using site- or central-based endoscopy evaluation.
Methods
This post hoc analysis of data fromEXTEND (extend the safety and efficacy of adalimumab through endoscopic healing), a placebo (PBO)-controlled, randomized trial of adalimumab (ADA) for mucosal healing, included adults with moderate-to-severe CD. Subsets of patients meeting specified Simplified Endoscopic Score for CD (SES-CD) inclusion criteria, according to site or central reading, and baseline stool frequency (SF) and/or abdominal pain score (AP) thresholds were evaluated. Various endpoint definitions based on the Crohn's Disease Activity Index (CDAI), its SF and AP components, SES-CD, and composite endpoints were compared between treatment groups.
Results
Increased stringency of Week 12 clinical endpoints compared to CDAI<150 to SF≤3.0/1.5&AP≤1.0 reduced PBO response rates by ≥12% and increased treatment effects by ≤10%. Amending the SES-CD endpoint from ≤4 to ≤2 reduced the treatment effect from 24% to 8%. Composite endpoints further diminished response rates and effect sizes. Site-based evaluation was associated with lower remission rates versus central reading in the PBO group and, thus, greater ADA-related treatment effects.
Conclusions
This analysis is the first to demonstrate that increasing the stringency of clinical and endoscopic endpoint definitions in CD trials, especially lowering SF or SES-CD definitions, reduces the ability to detect treatment-related change in CD activity; focus on endpoints that reflect clinical change is warranted.
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10.1093/ibd/izx082
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pubmed_940_5659
|
Type I collagen fibers account for 90% of the organic matrix of bone. The degradation of this collagen is a major event during bone resorption, but its mechanism is unknown. A series of data obtained in biological models strongly suggests that the recently discovered cysteine proteinase cathepsin K plays a key role in bone resorption. Little is known, however, about the actual action of cathepsin K on type I collagen. Here, we show that the activity of cathepsin K alone is sufficient to dissolve completely insoluble collagen of adult human cortical bone. We found that the collagenolytic activity of cathepsin K is directed both outside the helical region of the molecule, i.e. the typical activity of cysteine proteinases, and at various sites inside the helical region, hitherto believed to resist all mammalian proteinases but the collagenases of the matrix metalloproteinase family and the neutrophil elastase. This property of cathepsin K is unique among mammalian proteinases and is reminiscent of bacterial collagenases. It is likely to be responsible for the key role of cathepsin K in bone resorption.
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10.1074/jbc.273.48.32347
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pubmed_416_15253
|
Intravenous (IV) administration of anti-D in patients with autoimmune thrombocytopenia (AITP) may result in severe hemolysis and even death. Over a 3-year period, we gave anti-D only subcutaneously (SC), and none of our patients have developed any acute adverse reaction. Most importantly, SC delivery of anti-D produces largely the same beneficial effect as obtained by IV anti-D. We recommend replacement of IV administration of anti-D by SC administration in AITP.
|
10.1002/pbc.21006
|
pubmed_42_22076
|
Most patients with severe acute pericarditis should be hospitalized for complete diagnosis and observation for complications, particularly effusion and tamponade. Therapy should be directed at a specific inciting etiologic agent, if identified. In all patients, anti-inflammatory and symptomatic treatment should aim at alleviating pain, fever, and malaise, using nonsteroidal anti-inflammatory drugs (NSAIDs) as the mainstays. Choice of treatment should be individualized, but indomethacin should be avoided in adults, if possible, because of its deleterious effect on coronary flow. Colchicine added to NSAIDs or as monotherapy is effective both for the initial attack and to prevent recurrences. Corticosteroids should be used only as a last resort (eg, for severe illness resistant to NSAIDs) or to treat specific inciting illnesses.
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10.1007/s11936-999-0009-5
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pubmed_859_1804
|
Parkinson's disease is a common progressive and multifactorial neurodegenerative disease, characterized by the loss of midbrain dopaminergic neurons. Numerous pathological processes including, inflammation, oxidative stress, mitochondrial dysfunction, neurotransmitter imbalance, and apoptosis as well as genetic factors may lead to neuronal degeneration. With the emergence of aging population, the health problem and economic burden caused by PD also increase. Phosphatidylinositol 3-kinases-protein kinase B (PI3K-AKT) signaling pathway regulates signal transduction and biological processes such as cell proliferation, apoptosis and metabolism. According to reports, it regulates neurotoxicity and mediates the survival of neurons. Accumulating evidences indicate that some natural products can play a neuroprotective role by activating PI3K-AKT pathway, providing an effective resource for the discovery of potential therapeutic drugs. The current review provides an overview of the PI3K-AKT signaling pathway and review the relationship between this signaling pathway and PD.
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10.1016/j.yexmp.2022.104846
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pubmed_300_6629
|
BACKGROUND
With advance of age, alterations in bone quality, quantity and microarchitecture render osteoporotic trabecular bone become more sensitive to local failure. The aims of the present study were to clarify the extent to which the distribution of tissue-level stresses and strains was affected by structural changes and the extent to which osteoporotic acetabular trabecular bone was damaged at small strains.
METHODS
Using a DAWING 4000A supercomputer, nonlinear micro-finite element (microFE) analyses were performed to calculate the tissue-level strains and stresses for each element in the trabecular bone of one osteoporotic acetabulum at small strains to quantify the tissue-level damage accumulation and mechanical properties.
RESULTS
In contour plots of the tissue, maximum principal logarithmic strains, high tissue-level strains, both compressive and tensile, were observed in the osteoporotic trabecular bone at small apparent strains from 0.2% to 0.5% strain. The compressive apparent stress-strain curve showed typical nonlinear behavior and tangent modulus reduction with increasing strains. The microdamage curve suggested that microdamage began at 0.2% apparent strain in the osteoporotic trabecular bone and increased sharply, although very few microfractures occurred. The quartiles of the maximum principal logarithmic strains, minimum principal logarithmic strains and Von Mises stresses increased nonlinearly. For the inter-quartile range of the Von Mises stresses, a leap occurred at small strains ranging from 0.2% to 0.3% while microdamage commenced.
CONCLUSIONS
Extensive microdamage was primarily responsible for the large loss in apparent mechanical properties that occurred in the trabecular bone of the osteoporotic acetabulum at small strains. With increasing apparent strains, continuous nonlinear increments of tissue-level strains and stresses resulted in microdamage that propagated throughout the specimen with very few microfractures.
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pubmed_300_6629
|
pubmed_1108_12642
|
Borrelia lusitaniae is an Old World species of the Lyme borreliosis (LB) group of tick-borne spirochetes and prevails mainly in countries around the Mediterranean Basin. Lizards of the family Lacertidae have been identified as reservoir hosts of B. lusitaniae. These reptiles are highly structured geographically, indicating limited migration. In order to examine whether host geographic structure shapes the evolution and epidemiology of B. lusitaniae, we analyzed the phylogeographic population structure of this tick-borne bacterium using a recently developed multilocus sequence typing (MLST) scheme based on chromosomal housekeeping genes. A total of 2,099 questing nymphal and adult Ixodes ricinus ticks were collected in two climatically different regions of Portugal, being approximately 130 km apart. All ticks were screened for spirochetes by direct PCR. Attempts to isolate strains yielded 16 cultures of B. lusitaniae in total. Uncontaminated cultures as well as infected ticks were included in this study. The results using MLST show that the regional B. lusitaniae populations constitute genetically distinct populations. In contrast, no clear phylogeographic signals were detected in sequences of the commonly used molecular markers ospA and ospC. The pronounced population structure of B. lusitaniae over a short geographic distance as captured by MLST of the housekeeping genes suggests that the migration rates of B. lusitaniae are rather low, most likely because the distribution of mediterranean lizard populations is highly parapatric. The study underlines the importance of vertebrate hosts in the geographic spread of tick-borne microparasites.
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10.1371/journal.pone.0004002
|
pubmed_499_10834
|
BACKGROUND
The World Health Organization World Malaria Report of 2019 indicated an estimated 228 million cases of malaria occurred worldwide in 2018. More than 75% of the total area of Ethiopia is malarious, making malaria a leading public health problem in Ethiopia. Adherence to clinical guidelines improves the quality of care received by patients, thus improving patient outcomes. This study investigates healthcare workers' adherence to malaria testing and treatment guidelines in selected private clinics of Gambela Town, Ethiopia.
METHODS
A mixed study design involving a retrospective review of 425 patient files and 20 healthcare worker interviews in private clinics was implemented. Data were collected using pre-tested data collection forms. The collected data were then cleaned and entered into statistical software for analysis, with a level of significance set at < 0.05. A qualitative analysis was also conducted using healthcare worker interviews to identify the existing barriers to guideline adherence.
RESULTS
Among the 430 cases of suspected malaria, only 65% were tested for malaria. Of those tested, 75% tested positive and 25% tested negative. The most common co-morbidity in patients treated for malaria was anaemia (30%), followed by gastroenteritis (10%). Patients with co-morbidities were more likely to receive appropriate treatment (p = 0.03) compared to those without co-morbidities. All healthcare workers interviewed were aware of the existence of the malaria treatment guidelines. However, many were not aware of the contents of the guidelines and only 40% had been trained to understand the guidelines. Overall, 85% of the workers claimed to adhere to guidelines, with 15% claiming non-adherence.
CONCLUSION
The gap between knowledge of the malaria treatment guidelines and their application by healthcare workers remains wide. The level of knowledge of these guidelines was also low. Continuous training, follow-up, supportive supervision, and improved adherence to the malaria guidelines are therefore recommended.
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10.1186/s12936-022-04206-6
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pubmed_906_22745
|
Upon contact with intestinal epithelial cells, Salmonella enterica serovar spp. inject a set of bacterial proteins into host cells via the bacterial SPI-1 type III secretion system. SopE, SopE2 and SopB, activate CDC42 and Rac to initiate actin cytoskeleton rearrangements. SipA and SipC, two Salmonella actin-binding proteins, directly modulate host actin dynamics to facilitate bacterial uptake. SptP promotes the recovery of the actin cytoskeleton rearrangements by antagonizing CDC42 and Rac. Therefore, Salmonella-induced reversible actin cytoskeleton rearrangements are the result of two coordinated steps: (i) stimulation of host signal transduction to indirectly promote actin rearrangements and (ii) direct modulation of actin dynamics.
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10.1016/s1286-4579(01)01489-7
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pubmed_358_21846
|
The occurrence and relative positions of cysteine residues were investigated in proteins of various species. Considering random mathematical occurrence for an amino acid coded by two codons (3. 28%), cysteine is underrepresented in all organisms investigated. Representation of cysteine appears to correlate positively with the complexity of the organism, ranging between 2.26% in mammals and 0. 5% in some members of the Archeabacteria order. This observation, together with the results obtained from comparison of cysteine content of various ribosomal proteins, indicates that evolution takes advantage of increased use of cysteine residues. In all organisms studied except plants, two cysteines are frequently found two amino acid residues apart (C-(X)(2)-C motif). Such a motif is known to be present in a variety of metal-binding proteins and oxidoreductases. Remarkably, more than 21% of all of cysteines were found within the C-(X)(2)-C motifs in ARCHEA.: This observation may indicate that cysteine appeared in ancient metal-binding proteins first and was introduced into other proteins later.
|
10.1093/oxfordjournals.molbev.a026406
|
pubmed_27_19335
|
In this study, the possible intervention of VIP (Vasoactive Intestinal Peptide), beta-endorphine, glycocorticoids and dopamine, in postnatal lactotrophs hypoactivity at the rat, was investigated. Our results show that the injection of VIP (40 micrograms/kg), beta-endorphine (125 micrograms/kg) or its antagonist, naloxone (2 mg/kg), does not provide a change in serum PRL before or after ether stress at 6-day-old rats. However, after adrenalectomy, 6 day-old neonates became sensitive to ether stress as do adults, while acute treatment with dexamethasone (2 mg/kg) or dopamine (1 mg/kg), abolished this response completely. Sulpiride injection (1 mg/kg), on the contrary potentialized response. This lactotroph insensitiveness to ether stress, TRH, VIP, and beta-endorphine, during the beginning of postnatal life in the rat, might be explained, partially, by the failure of stimulatory factors "PRF" (Prolactin Releasing Factors), together with strength of inhibitory factors "PIF" (Prolactin Inhibitory Factors), such as dopamine and glycocorticoids.
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pubmed_27_19335
|
pubmed_147_10536
|
The article presents the priority directions of development and improvement of organization of specialized out-patient care of oncologic patients with propose to enhance quality of their life.
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pubmed_147_10536
|
pubmed_841_22107
|
OBJECTIVE
To develop a real-time PCR technique for detection of the insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) gene.
DESIGN AND METHODS
Three primers were designed for performing real-time PCR in the presence of SYBR Green I as flurochrome followed by melting curve analysis. Forty human genomic DNA that have been genotyped by two-rounds of conventional PCR were used for evaluation of this technique.
RESULTS
Melting curve analysis indicated the melting peak at 73.9 degrees C and 76.2 degrees C corresponding to the presence of I and D alleles, respectively. Comparable genotyping results were obtained by both conventional and real-time PCR. Besides, the mistyping of ID allele individuals by the first run of conventional PCR were accurately genotyped by single-tube real time PCR.
CONCLUSIONS
The real-time PCR method presented in this study provides a rapid and sensitive way for genotyping of ACE gene that may be suitable for large-scale clinical and epidemiologic study.
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10.1016/s0009-9120(01)00281-8
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pubmed_856_9455
|
Despite that commuters spend only 5.5% of their time in cabin vehicles, their exposure to harmful air pollutants, originated from the vehicle itself, and traffic emission is considered significant. In this study, two passenger cars with different type of fuels were investigated in terms of air quality and thermal comfort of their cabin. Investigation was performed in the city of Kozani, Northern Greece. Moreover, air samples near the exhausts were taken, in order to compare concentration of compounds found indoors. Twelve volatile organic compounds and CO2 were measured inside the cabin when the cars were stopped, when idle and when they were cruising in medium and heavy traffic roads, under various ventilated conditions. Thermal comfort was investigated while driving the cars through the city traffic. Results showed that the air around the diesel exhaust is less affected by emissions from the engine compared to LPG fuel. This is reflected to the TVOC measured into the cabin. Results also revealed that the air quality of a diesel fuel moving car with open windows is only affected by the traffic emissions from neighbouring vehicles, while for the car with LPG fuel, the self-pollution from its own exhaust might contribute together with the outdoor air.
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10.1007/s11356-021-14349-9
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pubmed_377_6608
|
Monocyte chemoattractant protein-1 (MCP-1/CCL2) has a critical role in the development of various renal diseases. Data from disease specific experimental animal models and clinical studies confirm that MCP-1 plays an important part in the pathogenesis of renal diseases. The action of MCP-1 in these studies has been shown to be more complex than the traditional concept of monocyte/macrophage recruitment to the inflammatory site. MCP-1 is expressed in renal tissues and it is detectable in urine of patients with a variety of renal diseases. Measurement of urinary levels of MCP-1 can provide valuable information not only for the diagnosis of active renal disease, but also for monitoring of response to therapy. Urinary MCP-1 measurement can provide help with evaluation of the prognosis in various renal diseases. Furthermore, selective targeting of MCP-1 could be an effective treatment in suppressing a number of renal diseases as blocking MCP-1 has already been shown to ameliorate renal diseases in experimental animal models. The advantage of measuring urinary MCP-1 rather than the conventional markers must now be validated using a larger cohort of patients in different renal diseases. Also the therapeutic potential of MCP-1 targeting agents needs to be investigated in clinical studies.
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10.1016/j.cca.2011.07.023
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pubmed_788_22547
|
Polypropyleneglycol (PPG) was used as a dispersion medium for the preparation of microspheres (MS) consisting of starch, gelatin, whey protein or dextran. Aqueous solutions of the polymers were dispersed in PPG at various initial temperatures and then the systems were cooled to 0.5 degrees C to allow water in the dispersed phase to dissolve in PPG. The particle size of the starch-MS was dependent on the initial temperature of PPG in the preparation process. There were two different processes for particle generation in the procedure. One of them was via the formation of a temporary emulsion during the early phase of dispersion of the aqueous polymer solution into PPG. The other was via the stable emulsion in which the aqueous polymer solution was dispersed in water-saturated PPG. The particle size generated in the former process was dependent on the initial temperature: a high temperature gave large particles but a low temperature gave small particles, while that in the latter process was temperature-independent. This preparation method for MS will be useful for the formulation of heat-sensitive material, such as protein-containing drugs.
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10.1248/cpb.55.403
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pubmed_50_2287
|
Colloidal crystals are often prepared by evaporation from solution, and there is considerable interest to link the processing conditions to the crystal morphology and quality. Here, we study the evaporation-induced assembly of colloidal crystals using massive-scale nonequilibrium molecular dynamics simulations. We apply a recently developed machine-learning technique to characterize the assembling crystal structures with unprecedented microscopic detail. In agreement with previous experiments and simulations, faster evaporation rates lead to earlier onset of crystallization and more disordered surface structures. Surprisingly, we find that collective rearrangements of the bulk crystal during later stages of drying reduce the influence of the initial surface structure, and the final morphology is essentially independent of the evaporation rate. Our structural analysis reveals that the crystallization process is well-described by two time scales, the film drying time and the crystal growth time, with the latter having an unexpected dependence on the evaporation rate due to equilibrium thermodynamic effects at high colloid concentrations. These two time scales may be leveraged to control the relative influence of equilibrium and nonequilibrium growth mechanisms, suggesting a route to rapidly process colloidal crystals while also removing defects. Our analysis additionally reveals that solvent-mediated interactions play a critical role in the crystallization kinetics and that commonly used implicit-solvent models do not faithfully resolve nonequilibrium processes such as drying.
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10.1063/1.5043401
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pubmed_82_18361
|
Human exposure to methylating agents appears to be widespread, as indicated by the frequent occurrence of methylated DNA adducts in human DNA. The high incidence of methylated DNA adducts even in humans thought not to have suffered extensive exposure to environmental methylating agents implies that chemicals of endogenous origin, probably N-nitroso compounds such as the strongly carcinogenic N-nitrosodimethylamine (NDMA), may be primarily responsible for their formation and raises the question of the carcinogenic risks associated with such exposure. In addition to accumulation of DNA damage, other factors (such as induced cell proliferation) appear to be important in determining the probability of induction of mutation or cancer by NDMA, implying that high to low dose risk extrapolations should not be based on the assumption of dose- or even adduct-linearity. Comparative studies of the accumulation and repair of methylated adducts in humans and animals treated with methylating cytostatic drugs do not reveal significant species differences. Based on this and the dosimetry of adduct accumulation in rats chronically exposed to very low doses of NDMA, it is suggested that the exposure needed to account for the levels of adducts found in human DNA may be of the order of hundreds of micrograms NDMA (or equivalent) per day, a level of exposure which may well represent a significant carcinogenic hazard for man.
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10.1016/s0027-5107(98)00130-4
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pubmed_67_9177
|
Biodiversity promotes ecosystem function in experiments, but it remains uncertain how biodiversity loss affects function in larger-scale natural ecosystems. In these natural ecosystems, rare and declining species are more likely to be lost, and function needs to be maintained across space and time. Here we explore the importance of rare and declining bee species to the pollination of three wildflowers and three crops using large-scale (72 sites across 5,000 km2 ), multi-year datasets. Half of the sampled bee species (82/164) were rare or declining, but these species provided only ~15% of overall pollination. To determine the number of species important to ecosystem function, we used two methods of 'scaling up', both of which have previously been used for biodiversity-function analysis. First, we summed bee species' contributions to pollination across space and time and then found the minimum set of species needed to provide a threshold level of function across all sites; according to this method, effectively no rare and declining bee species were important to pollination. Second, we account for the "insurance value" of biodiversity by finding the minimum set of bee species needed to simultaneously provide a threshold level of function at each site in each year. The second method leads to the conclusion that 25 rare and eight declining bee species (36% and 53% of all rare and declining bee species, respectively) are included in the minimum set. Our findings provide some of the strongest evidence yet that rare and declining species are key to meeting threshold levels of ecosystem function, thereby providing a more direct link between real-world biodiversity loss and ecosystem function. This article is protected by copyright. All rights reserved.
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10.1002/ecy.3899
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pubmed_222_20294
|
Type II diabetic patients and others with insulin resistance are at risk for development of hypertension characterized by elevated peripheral vascular resistance and loss of insulin's normal vasodilating activity. Oral antidiabetic drugs have recently been recognized to have disparate effects on arterial pressure in such patients and in related rodent models. Sulfonylureas (e.g., glyburide), which stimulate insulin secretion, have been reported either to increase or not to affect arterial pressure, whereas nonsulfonylurea agents with insulin-sensitizing properties, the biguanide metformin and various thiazolidinediones (eg, pioglitazone), have been reported to decrease arterial pressure in humans and rodents. To help elucidate these disparate effects, we investigated these agents for direct actions on arterial vascular contractility and its sensitivity to insulin. Preincubation of intact rat tail arterial tissue rings for 2 hours with known therapeutically effective antidiabetic concentrations of metformin and pioglitazone significantly attenuated the force of contractions produced by either potassium (membrane depolarization) or norepinephrine ([NE] adrenergic receptor activation). Glyburide did not influence these contractions. Preincubation with metformin also induced an attenuating (vasodilating-like) action of insulin on arterial tissue rings contracted by potassium. Conversely, glyburide induced an accentuating action of insulin on potassium-mediated contractions. These results are consistent with measures of vascular function obtained in the past after oral administration of the drugs, which suggested but did not prove that they may exert direct effects on arterial vascular contractility. Thus, metformin and thiazolidinediones may decrease arterial pressure partly by direct vasorelaxant mechanisms, with metformin having an additional effect of inducing vasorelaxation by insulin. In contrast, sulfonylureas may directly induce a paradoxical vasoconstrictor response to insulin.
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10.1016/s0026-0495(97)90217-1
|
pubmed_931_11225
|
Leadership in Maternal and Child Health (MCH) requires a repertoire of skills that transcend clinical or academic disciplines. This is especially true today as leaders in academic, government and private settings alike must respond to a rapidly changing health environment. To better prepare future MCH leaders we offer a framework of MCH leadership competencies based on the results of a conference held in Seattle in 2004, MCH Working Conference: The Future of Maternal and Child Health Leadership Training. The purpose of the conference was to articulate cross-cutting leadership skills, identify training experiences that foster leadership, and suggest methods to assess leadership training. Following on the work of the Seattle Conference, we sub-divide the 12 cross-cutting leadership competencies into 4 "core" and 8 "applied" competencies, and discuss this distinction. In addition we propose a competency in the knowledge of the history and context of MCH programs in the U.S. We also summarize the conference planning process, agenda, and work group assignments leading to these results. Based on this leadership competency framework we offer a definition of an MCH leader, and recommendations for leadership training, assessment, and faculty development. Taken as a set, these MCH leadership competencies point towards the newly-emerging construct of capability, the ability to adapt to new circumstances and generate new knowledge. "Capstone" projects can provide for both practice and assessment of leadership competencies. The competency-based approach to leadership that has emerged from this process has broad relevance for health, education, and social service sectors beyond the MCH context.
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10.1007/s10995-006-0170-3
|
pubmed_482_10790
|
The objective of this work was to formulate casein (CAS) nanocarriers for the dissolution enhancement of poorly water soluble drug celecoxib (CLXB). The CLXB loaded CAS nanocarriers viz., nanoparticles, reassembled CAS micelles and nanocapsules were prepared using sodium caseinate (SOD-CAS) as a carrier to enhance the solubility of CLXB. The prepared formulations were characterized for particle size, polydispersity index, zeta potential, percentage entrapment efficiency, and surface morphology for the selection of best formulation. Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray powder diffraction study was used to for the confirmation of encapsulation of CLXB. Further,in vitro drug dissolution, ex-vivo permeation studies on chicken ileum and stability studies were carried out. The CLXB loaded casein nanoparticles (CNP) (batch A2) showed a particle size diameter 216.1 nm, polydispersity index 0.422 with percentage entrapment efficiency of 90.71% and zeta potential of -24.6 mV. Scanning electron microscopy of suspension confirmed globular shape of CNP. Thein vitro release data of optimized batch followed non Fickian diffusion mechanism. The ex vivo permeation studies on chicken ileum of CLXB loaded CNP showed permeation through mucous membrane as compared to pure CLXB. The apparent permeability of best selected freeze dried CLXB loaded CNP (batch A2) was higher and gradually increased from 0.90 mg/cm2 after 10 min to a maximum of 1.95 mg/cm2 over the subsequent 90 min. A higher permeation was recorded at each time point than that of the pure CLXB. The study explored the potential of CAS as a carrier for solubility enhancement of poorly water soluble drugs.
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10.34172/apb.2020.049
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pubmed_154_11429
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Solid-phase microextraction (SPME) coupled to high-performance liquid chromatography (HPLC) with ultraviolet (UV) and electrochemical detection (ED) has been applied to determine 11 phenolic compounds considered priority pollutants by the US Environmental Protection Agency. 85 microm polyacrylate fibers were used to extract the analytes from the aqueous samples. Two different designs of the liquid chromatograph were compared in combination with SPME. Dynamic and static modes of desorption in both HPLC designs were compared and the variables affecting both absorption and desorption processes in SPME-HPLC were optimized. Static desorption in both HPLC systems showed better recoveries for the phenolic compounds. The performance of the SPME-HPLC-UV-ED method was evaluated with river water and wastewater samples. The method enabled the determination of phenolic compounds at low levels in these water samples.
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10.1016/s0021-9673(02)00113-9
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pubmed_969_19118
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Ethacrynic acid [2,3-dichloro-4-(2-methylene-1-oxobutyl)phenoxyl] acetic acid, is a water-soluble diuretic agent that has been shown to potentiate the in vitro cytotoxicity of chemotherapeutic agents in established cell lines. We used the differential staining cytotoxicity (DiSC) assay to determine whether ethacrynic acid at 1 and 3.3 microM would potentiate the cytotoxicity of nitrogen mustard and/or doxorubicin in primary cultures of hematologic neoplasms from heavily pretreated patients and in normal peripheral blood lymphocytes. At 3.3 microM, ethacrynic acid was toxic to 8 of 24 (33%) tumor specimens studied. In subsequent studies, ethacrynic acid at 1 microM was toxic to only 2 of 54 (4%) tumor specimens. Significant enhancement for doxorubicin or nitrogen mustard was confined to lymphatic malignancies and to normal peripheral blood lymphocytes. Interspecimen variability was observed, with no enhancement in most individual specimens, 2-fold enhancement in some specimens, and 4-fold enhancement in occasional specimens. Clinical trials will be required to determine whether the observed in vitro activity for ethacrynic acid is associated with clinical benefit in unselected or assay-selected patients.
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10.1007/BF02897285
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pubmed_400_3917
|
The prevalence of depression, erectile dysfunction (ED), and coronary heart disease (CHD) increases with age, and the symptoms related to these three illnesses are closely interlinked. The term "DEC syndrome" is introduced to refer to this triad of comorbid conditions. When a patient presents with one component of the DEC syndrome, physicians should also screen for the other two components. Studies have shown that depression may predispose an individual to an increased risk of developing CHD, and older men with CHD are more likely to be depressed. Likewise, patients with ED are more likely to be clinically depressed, and patients with clinical depression often have ED. Furthermore, patients presenting with ED are often hypertensive, and thus have a significantly higher prevalence of cardiovascular complications. Multifactorial problems require multifactorial approaches, and the care of older men can improve if physicians are aware of this interlinked syndrome.
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pubmed_400_3917
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pubmed_678_22902
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The formation and distribution of microgel-lysozyme complexes were identified by confocal laser scanning microscope (CLSM). The structure of lysozyme in the microgel was investigated by Fourier transform infrared (FT-IR) spectroscopy and Raman spectra. In vitro release of lysozyme from the microgel-lysozyme complexes was estimated. The structure of lysozyme released from stomach juice was further evaluated by circular dichroism (CD). The CLSM images showed that microgel-lysozyme complexes was formed and the lysozyme distributed quite homogeneously over the microgel particles. The FT-IR and Raman spectra indicated that lysozyme secondary structure maintained unchanged in the microgels. The microgels could be used as a carrier system to guard against the early release of lysozyme and protect lysozyme in the stomach and deliver targeted object to the intestine, as confirmed by the results of in vitro release and CD. This carboxymethyl starch-based microgel had potential as a specific delivery system for gastrointestinal environment.
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10.1016/j.foodchem.2017.01.073
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pubmed_428_20629
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Phosphate is absorbed through the gut, stored in the bone and reabsorbed through the proximal renal tubule. More importantly, PTH and FGF23 have been identified as the main phosphaturic factors that control the expression of the phosphate co-transporters NaPi-IIa et IIc. By allowing the adjustment of the urinary phosphate reabsorption, these two phosphatonins play a major role in bone and tooth mineralization and growth. Recently, novel therapies have successfully targeted the FGF23 signaling pathway to treat the hypophosphatemia in patients affected with molecular defects of this pathway (mutations in the PHEX gene).
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10.1016/S0003-4266(17)30076-8
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pubmed_630_12957
|
This study evaluated the influences of accelerated aging on the mechanical properties of veneering ceramics used for zirconia frameworks. Five different veneering ceramics for zirconia frameworks were used. Twenty specimens were fabricated for each veneering ceramic. All specimens were divided into two groups. One was subjected to accelerated aging and the other was used as a control. Accelerated aging was performed in distilled water for 5 h at 200ºC and 2 atm. The density, open porosity, surface roughness, three-point flexural strength, and Vickers hardness were measured. The results showed that the density, open porosity, and surface roughness of all examined veneering ceramics were changed by the accelerated aging process. Accelerated aging was also found to have a positive effect on strength and a negative effect on the hardness.
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10.4012/dmj.2015-115
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pubmed_913_6885
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Extraperitoneal, perivesical pelvic effusions may be hemorrhagic or uriniferous, the latter resulting from extraperitoneal rupture of the bladder or disruption of the posterior urethra. The effusions may be recognized on anteroposterior radiographs of the pelvis by (a) displacement of the bladder (small effusion); (b) obliteration of the normal soft-tissue anatomy within the pelvis (moderate effusion); and (c) upward displacement of the pelvic ileal loops and extension of the effusion into the flank stripes (large effusion). Perivesical effusions most frequently accompany anterior pelvic arch injuries, i.e., double vertical and Malgaigne fractures and fractures involving, or separation of, the pubic symphysis.
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10.1148/125.2.343
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pubmed_673_6823
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A mixture of aminopeptidase and neutral protease from the Aspergillus flavus mold obtained by chromatography on DEAE-Sephadex was fractionated by chromatography on the hydroxyalkyl methacrylate gel with chemically bonded 1,6 hexamethylene diamine and D-leucine. Aminopeptidase thus obtained was electrophoretically homogeneous. Conditions for chromatography were worked out allowing a one stage isolation of a highly active aminopeptidase sample directly from the alcoholic precipitate of the culture medium of the Aspergillus flavus mold.
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10.1016/0005-2795(76)90322-6
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pubmed_861_4294
|
Immune checkpoint inhibitors have revolutionized cancer treatment. However, many cancers are resistant to ICIs, and the targeting of additional inhibitory signals is crucial for limiting tumor evasion. The production of adenosine via the sequential activity of CD39 and CD73 ectoenzymes participates to the generation of an immunosuppressive tumor microenvironment. In order to disrupt the adenosine pathway, we generated two antibodies, IPH5201 and IPH5301, targeting human membrane-associated and soluble forms of CD39 and CD73, respectively, and efficiently blocking the hydrolysis of immunogenic ATP into immunosuppressive adenosine. These antibodies promoted antitumor immunity by stimulating dendritic cells and macrophages and by restoring the activation of T cells isolated from cancer patients. In a human CD39 knockin mouse preclinical model, IPH5201 increased the anti-tumor activity of the ATP-inducing chemotherapeutic drug oxaliplatin. These results support the use of anti-CD39 and anti-CD73 monoclonal antibodies and their combination with immune checkpoint inhibitors and chemotherapies in cancer.
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10.1016/j.celrep.2019.04.091
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pubmed_509_13550
|
OBJECTIVES
Infants who develop encephalopathy after perinatal asphyxia have an increased risk of death and adverse neurologic outcome. Conflicting results exist concerning outcome in healthy infants with metabolic acidosis at birth. The aim of the current study was to evaluate whether metabolic acidosis at birth in term infants who appear healthy is associated with long-term developmental abnormalities.
METHODS
From a population-based cohort (14,687 deliveries), 78 infants were prospectively identified as having metabolic acidosis (umbilical artery pH < 7.05 and base deficit in the extracellular fluid >12.0 mmol/L). Two matched controls per case were selected. The child health and school health care records were scrutinized for developmental abnormalities.
RESULTS
Outcome measures at 6.5 years of age for 227 of 234 children (97%) were obtained. No differences were found concerning neurologic or behavioral problems in need of referral action or neurodevelopmental diagnosis in comparison of control children with acidotic children who had appeared healthy at birth, ie, had not required special neonatal care or had no signs of encephalopathy.
CONCLUSIONS
Infants born with cord metabolic acidosis and who appear well do not have an increased risk for neurologic or behavioral problems in need of referral actions or special teaching approaches at the age of 6.5 years.
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10.1542/peds.2011-2831
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pubmed_752_8479
|
PURPOSE
To report the variability and progression of clinical presentation in three family members with spinocerebellar ataxia Type 7 including early recognizable features on retinal imaging and magnetic resonance imaging.
METHODS
Retrospective case series.
RESULTS
The proband, Patient 1 (mother) presented at age 26 with light perception vision. Initial examination was significant for optic disc pallor, vascular attenuation, and central macular atrophy. Two years later, her vision declined to no light perception, and fundus examination demonstrated marked progression of macular atrophy and peripheral bone spicule formation. Seven years after the onset of vision loss, neurologic examination demonstrated ataxia, dysarthria, and slowed saccades. Genetic testing of ATXN7 identified heterozygous 61-CAG trinucleotide repeat expansion confirming the diagnosis of spinocerebellar ataxia Type 7. Patient 2 (son) presented at age 11 with visual acuity of 20/300 bilaterally and decreased color vision. Funduscopic examination was notable for disc pallor, vascular attenuation, and peripheral pigmentary changes. Electroretinography demonstrated diminished rod and cone function, and Goldmann visual field testing revealed paracentral scotoma. Patient 3 (daughter) presented at age 14 with visual acuity of 20/50 bilaterally and minimal funduscopic changes. The only significant ophthalmic finding was retinal thinning with atrophy of the outer nuclear layer and subfoveal ellipsoid zone on optical coherence tomography. Early cerebellar volume loss was also noted on magnetic resonance imaging.
CONCLUSION
The clinical presentation of spinocerebellar ataxia Type 7 can vary widely even within the same family. In individuals with vision loss and normal fundus examination, careful evaluation of optical coherence tomography and brain magnetic resonance imaging facilitates early diagnosis and genetic testing.
|
10.1097/ICB.0000000000000248
|
pubmed_570_21469
|
AIM
To validate the construct validity of a new version of a Physical Activity Scale (PAS 2) for measuring average weekly physical activity of sleep, work, and leisure time to determine whether a further criterion validation is justified.
METHODS
The validity of responses to the questionnaire was evaluated by cognitive interviewing in 16 Danish men and women aged 21-70 years. Construct validity was validated in 342 men and women aged 35-66 years by assessing agreement between 24-h MET-scores obtained from average weekly physical activity measured by PAS 2 and a 24-h Physical Activity Scale (PAS 1), previously found to overestimate physical activity.
RESULTS
Cognitive interviewing revealed few problems in the questions on physical activity in different domains. No problems regarding the structure of the questionnaire were identified. The agreement between PAS 1 and PAS 2 MET-scores was high among participants with a PAS 1 24-h MET-score <45 MET-hours. Among participants with a PAS 1 24-h MET-score ≥45 MET-hours, the weekly-based scale, PAS 2, systematically estimated fewer MET-hours compared to the 24-h based scale, PAS 1. The difference increased proportionally with the average of the two MET-scores.
CONCLUSIONS
Few, small, lexical revisions were implemented into the new scale to improve the validity. As hypothesized, PAS 2 produced lower estimates of energy expenditure compared to PAS 1, indicating that the new scale may provide more valid measurements and that further validation against an objective criterion is justified.
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10.1177/1403494810380099
|
pubmed_314_21129
|
To examine the effect of co-extrusion on subsequent n-3 fatty acids in pig tissues, 8 pigs (barrows and gilts) were assigned to either a control treatment or one of nine treatments arranged in a 3 x 3 factorial design with 3 levels of co-extruded flaxseed (5%, 10% and 15%) and 3 durations of feeding (4, 8 and 12 weeks). Feed conversion improved slightly (P=0.01) with increasing dietary flaxseed but feeding flax for more than 8 weeks reduced average daily gain (P=0.02). In general, the duration and level of co-extruded flaxseed feeding affected (P<0.05) most fatty acids except for 22:6n-3 (P>0.05). Increasing the duration of flax feeding led to significant quadratic effects in backfat 18:3n-3 (P<0.001) and total n-3 fatty acids (P=0.002) when feeding 5% co-extruded flaxseed. Those increases were linear (P<0.001) when feeding 10% and 15% co-extruded flaxseed. Consequently feeding higher levels of flax for shorter periods vs. lower levels for longer periods appears to be more efficient at increasing n-3 fatty acids in pig backfat, but increases appeared to be less consistent. Moreover the addition of a 50:50 mix of extruded flax/peas to pig diets provided a highly available source of 18:3n-3 yielding n-3 fatty acid enrichments in backfat comparable to studies where extracted flaxseed oil was fed. Feeding flax co-extruded with field peas can be used to optimize consistent enrichments of n-3 fatty acids in back fat and relatively small amounts of this fat could be used to manufacture pork products to meet Canadian standards for n-3 fatty acid enrichment.
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10.1016/j.meatsci.2009.10.015
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pubmed_896_22707
|
We present in this paper a novel optic disc detection method based on a fully convolutional network and visual saliency in retinal fundus images. Firstly, we employ the morphological reconstruction-based object detection method to locate the optic disc region roughly. According to the location result, a 400 × 400 image patch that covers the whole optic disc is obtained by cropping the original retinal fundus image. Secondly, the Simple Linear Iterative Cluster approach is utilized to segment such an image patch into many smaller superpixels. Thirdly, each superpixel is assigned a uniform initial saliency value according to the background prior information based on the assumption that the superpixels located on the boundary of the image belong to the background. Meanwhile, we use a pretrained fully convolutional network to extract the deep features from different layers of the network and design the strategy to represent each superpixel by the deep features. Finally, both the background prior information and the deep features are integrated into the single-layer cellular automata framework to gain the accurate optic disc detection result. We utilize the DRISHTI-GS dataset and RIM-ONE r3 dataset to evaluate the performance of our method. The experimental results demonstrate that the proposed method can overcome the influence of intensity inhomogeneity, weak contrast, and the complex surroundings of the optic disc effectively and has superior performance in terms of accuracy and robustness.
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10.1155/2021/3561134
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pubmed_297_21860
|
BACKGROUND AND AIMS
Cannabis is one of the most commonly used substances among adolescents and young adults. Earlier age at cannabis initiation is linked to adverse life outcomes, including multi-substance use and dependence. This study estimated the heritability of age at first cannabis use and identified associations with genetic variants.
METHODS
A twin-based heritability analysis using 8055 twins from three cohorts was performed. We then carried out a genome-wide association meta-analysis of age at first cannabis use in a discovery sample of 24 953 individuals from nine European, North American and Australian cohorts, and a replication sample of 3735 individuals.
RESULTS
The twin-based heritability for age at first cannabis use was 38% [95% confidence interval (CI) = 19-60%]. Shared and unique environmental factors explained 39% (95% CI = 20-56%) and 22% (95% CI = 16-29%). The genome-wide association meta-analysis identified five single nucleotide polymorphisms (SNPs) on chromosome 16 within the calcium-transporting ATPase gene (ATP2C2) at P < 5E-08. All five SNPs are in high linkage disequilibrium (LD) (r2 > 0.8), with the strongest association at the intronic variant rs1574587 (P = 4.09E-09). Gene-based tests of association identified the ATP2C2 gene on 16q24.1 (P = 1.33e-06). Although the five SNPs and ATP2C2 did not replicate, ATP2C2 has been associated with cocaine dependence in a previous study. ATP2B2, which is a member of the same calcium signalling pathway, has been associated previously with opioid dependence. SNP-based heritability for age at first cannabis use was non-significant.
CONCLUSION
Age at cannabis initiation appears to be moderately heritable in western countries, and individual differences in onset can be explained by separate but correlated genetic liabilities. The significant association between age of initiation and ATP2C2 is consistent with the role of calcium signalling mechanisms in substance use disorders.
|
10.1111/add.14368
|
pubmed_1081_17281
|
OBJECTIVES
To identify which information items potential participants and research nurses rank as the most important, and the reasons for this, when considering participation in a randomised controlled trial.
DESIGN
Q-methodology approach alongside a think-aloud process. Using a vignette outlining a hypothetical trial, participants were asked to rank statements about informational items usually included in a participant information leaflet (PIL) on a Q-grid, while undertaking a real-time think-aloud process to elicit the underpinning decision processes. Analysis of quantitative data was conducted using descriptive statistics and qualitative data was coded using content analysis.
PARTICIPANTS
20 participants (10 potential trial participants and 10 research nurses).
SETTING
UK-based participants.
RESULTS
Ten research nurses and 10 potential trial participants provided data for the study. Both stakeholder groups ranked similar statements in their top three most important statements, with 'What are the possible disadvantages and risks of taking part?' featuring in both. However, considerable variability existed between the groups with regard to their ranking of statements of least importance. Participants identified that sufficient information to make a decision was secured using around 14 items. Participants also identified other items of importance not routinely included in PILs.
CONCLUSIONS
This study has provided a unique insight into how and why different trial stakeholder groups rank informational items currently contained within PILs. These results have implications for those developing future PILs and those who develop guidance on their content; PILs should focus most on the information items that potential trial participants want and need to make an informed choice about trial participation.
|
10.1136/bmjopen-2018-023303
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pubmed_714_14887
|
The mechanisms that regulate the transport of the macrophage class A scavenger receptor during ligand uptake were investigated. Kinetic analysis of the changes in receptor phosphorylation demonstrated that serine phosphorylation increased during the internalization of acetyl-low density lipoproteins (LDL) by macrophages. The increase was maximal at about 2.5 min after the initiation of ligand uptake. Oxidized LDL also stimulated serine phosphorylation, but the relative increase was smaller and the time to maximum was shorter. Receptor mutants expressed in Chinese hamster ovary and COS cells showed that elimination of the potential phosphorylation site at Ser(21) increased acetyl-LDL metabolism, whereas inactivation of the site at Ser(49) reduced acetyl-LDL uptake. The increase in uptake by the Ser(21) mutant was due to an increase in surface receptor expression. In contrast, elimination of the site at Ser(49) did not affect receptor expression but slowed receptor internalization. To identify potential internalization signal sequences, beta-turn structure in the cytosolic domain was targeted for mutagenesis. Disruption of one region near Asp(25) inhibited receptor activity. The studies support a model whereby receptor internalization requires the presence of an internalization signal motif but that the rate of receptor internalization is governed by the pattern of receptor phosphorylation induced by the ligand.
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10.1074/jbc.274.51.36808
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pubmed_916_4991
|
Inappropriate sinus tachycardia is characterized by an unexplained increase of the resting sinus rate (> 100 bpm) with excess increase in response to moderate activity (mean heart rate > 90 bpm/24 h). Affected patients may suffer from heart race, palpitations, fatigue, weakness and dizziness. The mechanisms underlying inappropriate sinus tachycardia and its long term prognosis are poorly understood. Thus, diagnosis and treatment are empiric and require the initial exclusion of potential causes of secondary sinus tachycardia. Therapeutic approaches include physical training, beta blockers or ivabradine. Radiofrequency catheter ablation should be restricted to patients with refractory and longstanding symptoms.
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10.1055/s-0041-101620
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pubmed_443_8986
|
BACKGROUND AND OBJECTIVE
We analyzed the factors that affected the number and quality of peripheral blood stem cells (PBSC) collected for transplant in order to establish a minimum threshold for rapid hematopoietic recovery.
DESIGN AND METHODS
From January 1995 to November 1996, a consecutive series of 67 patients, with hematologic and solid tumors underwent autologous PBSC transplantation. Collection of PBSC was performed after mobilization with granulocyte-colony stimulating factor (G-CSF) or with chemotherapy (CT) plus G-CSF. We calculated the factors that influenced PBSC collection, the kinetics of granulocyte and platelet recovery and the threshold value of CD34+ cells for a rapid recovery. The data were analyzed by means of multivariate Cox regression model and the receiver operating characteristic (ROC) methodology.
RESULTS
Our results showed that mobilization with chemotherapy plus G-CSF was associated with a higher yield of PBSC in comparison with mobilization with G-CSF alone. Disease status, fewer cycles of conventional prior chemotherapy and absence of prior radiation therapy also influenced the yield of PBSC. The number of CD34+ cells, CD34+CD33- cell subsets, the mobilization schedule, and the conditioning regimen correlated significantly with time to hematopoietic recovery. In the multivariate analysis only the CD34+CD33- cell content and the total number of CD34+ were related with rapid neutrophil and platelet recovery, respectively. Use of G-CSF after transplant significantly shortened the neutrophil recovery time only in patients transplanted with suboptimal dose of PBSC.
INTERPRETATION AND CONCLUSIONS
These data suggest the utility of quantitation of CD34+ cells subsets to predict quick engraftment.
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pubmed_443_8986
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pubmed_533_15636
|
Lack of collaboration between care teams and patients/families has been associated with delayed discharge from the hospital. In this study, we determine whether patients' awareness of the estimated date of discharge (EDD) was associated with a decrease in delayed discharge, and determine the factors associated with a delayed discharge. A total of 221 patients admitted to the General Medicine service between July and September 2014 were included in the study. Estimated date of discharge was identified within 36 hours of admission. The bedside nurse communicated this EDD to the patient/family. Patients were interviewed to identify whether they were aware of their EDD. Bedside nurses were interviewed to identify barriers to discharge. In our study, 49.8% of the patients had a delayed discharge. Patients who were aware of their EDD were less likely to have a delayed discharge (odds ratio [OR], 0.3 [95% confidence interval (CI), 0.1-0.6], p < .001). Patients who were discharged on Saturday or Sunday (OR, 4.8 [95% CI, 1.7-14.6], p < .001) and patients who were waiting for physicians' consult (OR, 4.5 [95% CI, 1.6-14.4], p = .007) were more likely to have a delayed discharge. Early identification of the EDD and communicating it with the care team and the patient/family, mobilizing resources for safe weekend discharges, and creating efficient process for consultations might decrease delayed discharges.
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10.1097/JHQ.0000000000000126
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pubmed_681_9295
|
The relative importance of calcium vs. vitamin D deficiency in the etiology of nutritional rickets in the tropics may be different in children compared with adolescents. We studied calcium intake, sun exposure, serum alkaline phosphatase, and 25 hydroxyvitamin D in 24 children and 16 adolescents with rickets/osteomalacia. The values were compared with those obtained in control subjects (34 children and 19 adolescents). We found that young children with rickets had lower calcium intake compared with controls (285 +/- 113 vs. 404 +/- 149 mg/day, p < 0.01), but similar sun exposure (55 +/- 28 vs. 56 +/- 23 min x m2/day) and 25 hydroxyvitamin D (49 +/- 38 vs. 61 +/- 36 nmol/l). Sixteen of 24 children with rickets had 25 hydroxyvitamin D above the rachitic range (> 25 nmol/l), in contrast to one of 16 adolescents. Adolescent patients had low calcium intake vs. controls (305 +/- 196 vs. 762 +/- 183 mg, p < 0.001), and lower sunshine exposure (16 +/- 15 vs. 27 +/- 17 min x m2/day, p < 0.01) and serum 25 hydroxyvitamin D (12.6 +/- 7.1 vs. 46 +/- 45.4 nmol/l, p < 0.001). The odds ratio for developing rickets with a daily calcium intake below 300 mg was 4.8 (95 per cent CI, 1.9 - 12.4, p = 0.001). Subjects with rickets were randomized to receive 1 g calcium daily, with or without vitamin D. Children showed complete healing in 3 months, whether they received calcium alone or with vitamin D. Adolescents showed no response to calcium alone, but had complete healing with calcium and vitamin D in 3-9 months (mean 5.3 months). Thus deficient calcium intake is universal among children and adolescents with rickets/osteomalacia. Inadequate sun exposure and vitamin D deficiency are important in the etiology of adolescent osteomalacia.
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10.1093/tropej/49.4.201
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pubmed_439_8495
|
This paper presents a comprehensive solution for distance estimation of the following vehicle solely based on visual data from a low-resolution monocular camera. To this end, a pair of vehicles were instrumented with real-time kinematic (RTK) GPS, and the lead vehicle was equipped with custom devices that recorded video of the following vehicle. Forty trials were recorded with a sedan as the following vehicle, and then the procedure was repeated with a pickup truck in the following position. Vehicle detection was then conducted by employing a deep-learning-based framework on the video footage. Finally, the outputs of the detection were used for following distance estimation. In this study, three main methods for distance estimation were considered and compared: linear regression model, pinhole model, and artificial neural network (ANN). RTK GPS was used as the ground truth for distance estimation. The output of this study can contribute to the methodological base for further understanding of driver following behavior with a long-term goal of reducing rear-end collisions.
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10.3390/s22072736
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pubmed_400_12540
|
In vivo microdialysis in combination with liquid chromatography/electrospray time-of-flight mass spectrometry was used to study the processing of LVV-hemorphin-7, an endogenous decapeptide with opioid activity, in rat brain and blood. A microdialysis probe (flow rate 0.4 microL/min) was used to both introduce LVV-hemorphin-7 into the striatum of the brain (1.0 pmol/microL) or the venous blood (10 pmol/microL) and to collect the metabolic products. LVV-hemorphin-7 was extracellularly metabolized in the striatum to form C-terminal fragments 2-10, 3-10, 4-10, 5-10, 6-10, 7-10, and N-terminal fragments 1-9, 1-8, 1-6. Infusion of the aminopeptidase inhibitor amastatin (1.0 pmol/microL) into the striatum, together with LVV-hemorphin-7, decreased the processing of LVV-hemorphin-7 to form C-terminal fragments 2-10, 3-10, 4-10, but increased the relative levels of fragment 5-10 and N-terminal fragments 1-9, 1-8 and 1-6. The major metabolic product from LVV-hemorphin-7 in the striatum was the C-terminal fragment 5-10, which may be processed by an endopeptidase not sensitive to amastatin. The LVV-hemorphin-7 infusion to the venous blood produced the C-terminal fragments 2-10, 3-10, 4-10, and 5-10, N-terminal fragment 1-9, and internal fragments 4-7 and 4-9. It is concluded that the combination of microdialysis and electrospray mass spectrometry provides a powerful tool for the study of extracellular metabolism and kinetic processes of complex reaction systems in vivo.
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10.1002/rcm.972
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pubmed_652_19324
|
In this study, the retention changes induced by frictional heating were evaluated for model small compounds (150-190Da) and a small protein, namely insulin (5.7kDa). For this purpose, the effect of longitudinal temperature gradient caused by frictional heating was experimentally dissociated from the combined effect of pressure and frictional heating, by working either in constant and variable inlet pressure modes. Various columns packed with core-shell and fully porous sub-2μm particles were tested. It appears that frictional heating was less pronounced on the column packed with smallest core-shell particles (1.3μm), compared to the ones packed with core-shell and fully porous particles of 1.7-1.8μm. This observation was attributed to the low permeability of this material and the fact that it can only be employed in a restricted flow rate range, thus limiting the generated heat power. In addition, the thermal conductivity of the solid silica core of superficially porous particles (1.4W/m/K) is known to be much larger than that of fully porous silica. Then, the heat dissipation is improved. However, if systems with higher pressure capability would be available and the mechanical stability of 1.3μm core-shell material was extended to e.g. 2000bar, the retention would be more severely impacted. At 2000bar, ∼4.4W heat power and +30°C increase at column outlet temperature is expected. Last but not least, when analyzing large molecules, the impact of pressure overcomes the frictional heating effects. This was demonstrated in this study with insulin (∼5.7kDa).
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pubmed_652_19324
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pubmed_742_22143
|
This paper describes, analyzes, interprets, and spells out some implications of a divorce as it was faced and handled by a pastor and congregation. The challenge to work creatively with divorce came when both the husband and wife wished to remain in the congregation as members. The paper briefly sets forth theological perspectives on marriage, divorce, and discipline in the Mennonite Church, a brief case history of the couple, a description of the group and ritual process with which the pastor and congregation responded, and the reflections of the couple and members a year later. The paper offers not a model but, rather, a symbol as presented in the title, "Falling Rings." It is hoped that the symbol will not only give rise to thought, but will also spark the imagination so as to enable other congregations to respond more assertively, creatively, and caringly to those who divorce in their midst.
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10.1007/BF01533123
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pubmed_166_21826
|
A growing number of nucleobase modifications in messenger RNA have been revealed through advances in detection and RNA sequencing. Although some of the biochemical pathways that involve modified bases have been identified, research into the world of RNA modification - the epitranscriptome - is still in an early phase. A variety of chemical tools are being used to characterize base modifications, and the structural effects of known base modifications on RNA pairing, thermodynamics and folding are being determined in relation to their putative biological roles.
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10.1038/nature21351
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pubmed_876_4319
|
A 76-year-old woman admitted to our hospital for jaundice had been treated for diabetes mellitus with insulin for 9 years and voglibose had been added for the 39 months preceding admission. Elevated serum bilirubin and transaminase concentration began to normalize with initiation of corticosteroid treatment 1 week after discontinuation of voglibose. In the in vitro testing of the patient's peripheral blood, lymphocytes showed stimulation by voglibose. In dramatic contrast to an initial liver biopsy specimen that demonstrated cholestasis with submassive and zonal necrosis, the follow-up specimen was normal 1 year later. We believe that patients treated with voglibose should be monitored long-term with monthly determinations of transaminases and bilirubin in serum.
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10.2169/internalmedicine.40.484
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pubmed_1033_12618
|
A national conference was held to review and assess data gathered since implementation of MELD and PELD and determine future directions. The objectives of the conference were to review the current system of liver allocation with a critical analysis of its strengths and weaknesses. Conference participants used an evidence-based approach to consider whether predicted outcome after transplantation should influence allocation, to discuss the concept of minimal listing score, to revisit current and potential expansion of exception criteria, and to determine whether specific scores should be used for automatic removal of patients on the waiting list. After review of data from the first 18 months since implementation, association and society leaders, and surgeons and hepatologists with wide regional representation were invited to participate in small group discussions focusing on each of the main objectives. At the completion of the meeting, there was agreement that MELD has had a successful initial implementation, meeting the goal of providing a system of allocation that emphasizes the urgency of the candidate while diminishing the reliance on waiting time, and that it has proven to be a powerful tool for auditing the liver allocation system. It was also agreed that the data regarding the accuracy of PELD as a predictor of pretransplant mortality were less conclusive and that PELD should be considered in isolation. Recommendations for the transplant community, based on the analysis of the MELD data, were discussed and are presented in the summary document.
|
10.1002/lt.20247
|
pubmed_1110_20063
|
The relative ranking of cirrhosis-related deaths differs between high-/middle-income countries. Gut microbiome is affected in cirrhosis and is related to diet. Our aim was to determine the effect of differing dietary habits on gut microbiota and clinical outcomes. Outpatient compensated/decompensated patients with cirrhosis and controls from Turkey and the United States underwent dietary and stool microbiota analysis. Patients with cirrhosis were followed till 90-day hospitalizations. Shannon diversity and multivariable determinants (Cox and binary logistic) of microbial diversity and hospitalizations were studied within/between groups. Two hundred ninety-six subjects (157 U.S.: 48 controls, 59 compensated, 50 decompensated; 139 Turkey: 46 controls, 50 compensated, 43 decompensated) were included. Patients with cirrhosis between cohorts had similar Model for End-Stage Liver Disease (MELD) scores. American patients with cirrhosis had more men, greater rifaximin/lactulose use, and higher hepatitis C/alcohol etiologies. Coffee intake was higher in Americans whereas tea, fermented milk, and chocolate intake were higher in Turkey. The entire Turkish cohort had a significantly higher microbial diversity than Americans, which did not change between their controls and patients with cirrhosis. In contrast, microbial diversity changed in the U.S.-based cohort and was the lowest in decompensated patients. Coffee, tea, vegetable, chocolate, and fermented milk intake predicted a higher diversity whereas MELD score, lactulose use, and carbonated beverage use predicted a lower microbial diversity. The Turkish cohort had a lower risk of 90-day hospitalizations. On Cox and binary logistic regression, microbial diversity was protective against 90-day hospitalizations, along with coffee/tea, vegetable, and cereal intake.
CONCLUSION
In this study of patients with cirrhosis and healthy controls from the United States and Turkey, a diet rich in fermented milk, vegetables, cereals, coffee, and tea is associated with a higher microbial diversity. Microbial diversity was associated with an independently lower risk of 90-day hospitalizations. (Hepatology 2018;68:234-247).
|
10.1002/hep.29791
|
pubmed_245_6556
|
Purpose
The purpose of this study was to characterize a novel finding that relative positions of choroidal and retinal vessels change over time in preterm infants and to identify factors associated with this finding using quantitative analysis.
Methods
Fundus images were obtained prospectively through a retinopathy of prematurity (ROP) cohort study. Images were excluded if choroidal vessels could not be identified. Changes in relative position of characteristic choroidal landmarks with respect to retinal vessels between two time points 5 to 7 weeks apart were measured. Univariate and multivariate regression analyses were performed to identify associated factors with the amount of change.
Results
The discovery and replication cohorts included 45 and 58 patients, respectively. Ninety-two of them (89%) were non-Hispanic Caucasians. Changes in relative position of choroidal versus retinal vessels were detected in all eyes of the discovery and replication cohorts (mean amount = 0.42 ± 0.12 and 0.35 ± 0.12 mm, respectively). On combined multiple regression analysis of the two cohorts, type 1 ROP, higher postmenstral age at the first time point, and shorter distance from optic disc to choroidal landmark were significantly associated with less change in relative position.
Conclusions
Choroidal vessels grow anteriorly with respect to retinal vessels at posterior pole in preterm infants, suggesting relatively faster peripheral growth of choroidal versus retinal vessels. Eyes with severe ROP showed less difference in growth, which might represent alterations in choroidal development due to advanced ROP. These findings may contribute to better understanding about the physiology of choroidal development and involvement in ROP.
|
10.1167/iovs.17-22687
|
pubmed_999_15114
|
Two aerobic granular sludge (AGS) sequential batch reactors were operated at a mild (15 °C) temperature for 180 days. One of those bioreactors was exposed to a mixture of diclofenac, naproxen, trimethoprim, and carbamazepine. The AGS system, operating under pressure from emerging contaminants, showed a decrease in COD, BOD5, and TN removal capacity, mainly observed during the first 100 days, in comparison with the removal ratios detected in the control bioreactor. After an acclimatisation period, the removal reached high-quality effluent for COD and TN, close to 95% and 90%, respectively. In the steady-state period, trimethoprim and diclofenac were successfully removed with values around 50%, while carbamazepine and naproxen were more recalcitrant. The dominant bacterial OTUs were affected by the presence of a mixture of pharmaceutical compounds, under which the dominant phylotypes changed to OTUs classified among the Pseudomonas, Gemmobacter, and Comamonadaceae. The RT-qPCR and qPCR results showed the deep effects of pharmaceutical compounds on the number of copies of target genes. Statistical analyses allowed for linking the total and active microbial communities with the physico-chemical performance, describing the effects of pharmaceutical compounds in pollution degradation, as well as the successful adaptation of the system to treat wastewater in the presence of toxic compounds.
|
10.3390/toxics9050093
|
pubmed_656_205
|
BACKGROUND
The COVID-19 pandemic has made a significant impact on all spheres of society. The objective of this study was to examine the impact of COVID-19 on the practices, finances, and social aspects of Brazilian vascular surgeons' lives.
METHODS
This is a descriptive analysis of the responses from Brazilian vascular surgeons to the cross-sectional anonymous Society for Vascular Surgery Wellness Task Force Pandemic Practice, Anxiety, Coping, and Support Survey for Vascular Surgeons disseminated 14-24 April 2020. Survey dissemination in Brazil occurred mainly via the Brazilian Society of Angiology and Vascular Surgery (SBACV) and social media. The survey evaluated the impact of the COVID-19 pandemic on vascular surgeons' lives by assessing COVID-19-related stressors, anxiety using theGeneral Anxiety Disorder (GAD)-7 scale, and coping strategies using the Brief Coping Orientation to Problems Experienced (Brief-COPE) inventory.
RESULTS
A total of 452 responses were recorded from Brazil, with 335 (74%) respondents completing the entire survey. The majority of respondents were males (N = 301, 67%) and practiced in an urban hospitals. The majority of respondents considered themselves at high risk to be infected with COVID-19 (N = 251, 55.8%), and just over half the respondents noted that they had adequate PPE at their primary hospital (N = 171, 54%). One hundred and nine (35%) surgeons confirmed that their hospitals followed professional surgical society guidelines for prioritizing surgeries during the pandemic. At the time of the survey, only 33 (10%) surgeons stated they have pre-operative testing of patients for COVID-19 available at their hospital. Academic vascular surgeons reported being redeployed more often to help with other non-vascular duties compared to community-based or solo practitioners (43% vs. 30% vs. 21% respectively, P = .01). Severe anxiety due to pandemic-related financial concerns was similar in those surgeons practicing solo compared to those in community- or academic-based/group practice (46% vs. 38% vs. 22%; P = .54). The respondents reported their anxiety levels as mild based on the stressors investigated instead of moderate-severe (54% vs. 46%; P = .04). Social media was utilized heavily during the pandemic, with video gatherings being the most commonly used tool (76%). Self-distraction (60%) and situational acceptance (81%) were the most frequently reported coping mechanisms used among Brazilian vascular surgeons.
CONCLUSION
The COVID pandemic has greatly affected healthcare providers around the world. At the time of this survey, Brazilian vascular surgeons are reporting low anxiety levels during this time and are using mostly active coping mechanisms.
|
10.1177/1708538120954961
|
pubmed_767_9736
|
Our purpose was to analyze associations between apparent diffusion coefficient (ADC) histogram analysis parameters and histopathologicalfeatures in head and neck squamous cell carcinoma (HNSCC). The study involved 32 patients with primary HNSCC. For every tumor, the following histogram analysis parameters were calculated: ADCmean, ADCmax, ADCmin, ADCmedian, ADCmode, P10, P25, P75, P90, kurtosis, skewness, and entropy. Furthermore, proliferation index KI 67, cell count, total and average nucleic areas were estimated. Spearman's correlation coefficient (p) was used to analyze associations between investigated parameters. In overall sample, all ADC values showed moderate inverse correlations with KI 67. All ADC values except ADCmax correlated inversely with tumor cellularity. Slightly correlations were identified between total/average nucleic area and ADCmean, ADCmin, ADCmedian, and P25. In G1/2 tumors, only ADCmode correlated well with Ki67. No statistically significant correlations between ADC parameters and cellularity were found. In G3 tumors, Ki 67 correlated with all ADC parameters except ADCmode. Cell count correlated well with all ADC parameters except ADCmax. Total nucleic area correlated inversely with ADCmean, ADCmin, ADCmedian, P25, and P90. ADC histogram parameters reflect proliferation potential and cellularity in HNSCC. The associations between histopathology and imaging depend on tumor grading.
|
10.18632/oncotarget.25284
|
pubmed_50_22445
|
BACKGROUND
While human papillomavirus (HPV) DNA testing offers high sensitivity for the detection of significant cervical disease, its specificity is suboptimal given the high prevalence of transient HPV infections (CIN1 or less). Biomarkers to identify those suffering from low grade disease from those with high grade disease could save healthcare costs and reduce patient anxiety.
OBJECTIVE
The objective of the present work was to develop and test an immunohistochemistry (IHC)-based dual viral and cellular biomarker strategy which was applicable to liquid based cytology (LBC) samples.
STUDY DESIGN
We developed a novel IHC assay for detection of HPV E4 and cellular minichromosome maintenance (MCM) proteins in routinely taken cervical LBC samples using cytospin-prepared slides. The assay was applied to a prospective cohort of Scottish women referred to a colposcopy clinic due to preceding cytological abnormalities. The performance of the biomarkers for detection of clinically insignificant (CIN1 or less) versus significant disease was determined.
RESULTS
A total of 81 women were recruited representing 64 cases of <=CIN1 and 28 of CIN2 + . Biomarker performance relative to histopathology outcomes showed high levels of MCM detection was significantly associated with CIN2+ (p = 0.03) while E4 was detected more frequently in <=CIN1 (p = 0.06).
CONCLUSIONS
Combined detection of a host proliferation marker and a marker of viral gene expression could allow triage of cases of clinically insignificant disease prior to colposcopy. However, there was overlap between distributions of MCM levels in CIN2+ and <=CIN1 suggesting that additional biomarkers would be required for improved specificity. Combined with cytospin-prepared slides this approach could provide a means of risk stratification of disease in low resource settings.
|
10.1016/j.jcv.2018.08.011
|
pubmed_40_24865
|
Three-dimensional reconstruction of human body from a living subject can be considered as the first step toward promoting virtual human project as a tool in clinical applications. This study proposes a detailed protocol for building subject-specific three-dimensional model of knee joint from a living subject. The computed tomography and magnetic resonance imaging image data of knee joint were used to reconstruct knee structures, including bones, skin, muscles, cartilages, menisci, and ligaments. They were fused to assemble the complete three-dimensional knee joint. The procedure was repeated three times with respect to three different methods of reference landmarks. The accuracy of image fusion in accordance with different landmarks was evaluated and compared with each other. The complete three-dimensional knee joint, which included 21 knee structures, was accurately developed. The choice of external or anatomical landmarks was not crucial to improve image fusion accuracy for three-dimensional reconstruction. Further work needs to be done to explore the value of the reconstructed three-dimensional knee joint for its biomechanics and kinematics.
|
10.1177/0954411913493723
|
pubmed_516_4036
|
A true collision tumor at the pyloric antrum of the stomach has been rarely described in literature. In this article, we report a gastric collision tumour comprising adenocarcinoma with carcinoid in a 48 year old man. The morphologic, immunohistochemical and electron microscopic findings of this rare case is discussed.
|
pubmed_516_4036
|
pubmed_281_7538
|
Biological motion perception is integral not only to survival but also to the social life of human beings. Identifying the underlying mechanisms and their associated neurobiological substrates has been a matter of investigation and debate for some time. Although, in general, it is believed that the integration of local motion and dynamic form cues in the brain empowers the visual system to perceive/recognize biological motion stimuli, some recent studies have indicated the importance of dynamic form cues in such a process. Inspired by the previous neurophysiologically plausible biological motion perception models, a new descriptive risk-averse Bayesian simulation model, capable of discerning a ball's direction from a set of complex biological motion soccer kick stimuli, is proposed. The model represents only the dorsal pathway as a motion information processing section of the visual system according to the two-stream theory. The stimuli used have been obtained from a previous psychophysical study on athletes in our lab. Furthermore, the acquired psychophysical data from that study have been used to re-enact human behavior using our simulation model. By adjusting the model parameters, the psychometric function of athlete subjects has been mimicked. A correlation analysis between human and simulation data shows a significant and robust correlation between angular thresholds and slopes of the psychometric functions of both groups. Although it is established that the visual system optimally integrates all available information in the decision-making process, the results conform to the speculations favoring motion cue importance over dynamic form by testing the limits in which biological motion perception only depends on motion information processing.
|
10.3390/biomimetics7040193
|
pubmed_664_21521
|
OBJECTIVE
To compare the effects of greenlight photoselective vaporization prostatectomy (PVP) and thulium laser vaporesection of the prostate (TmLRP) in the treatment of aged high-risk BPH patients with the prostate weighing > 80 g.
METHODS
We included in this study 118 high-risk BPH patients aged 62-96 (mean 76) years with the prostate heavier than 80 g, 82 treated by PVP and the other 36 by TmLRP. Then we compared the operation time, intraoperative bleeding, complications, short-term effectiveness, and surgical cost between the two groups.
RESULTS
All the patients tided over the perioperative period without blood transfusion and serious complications. The mean operation time, postoperative bladder irrigation time and surgical cost were significantly less in the TmLRP than in the PVP group (P < 0.05). Both the procedures remarkably improved the international prostatic symptom score (IPSS), quality of life (QOL), post void residual urine (PVR) and Qmax of the patients (P < 0.05), but with no significant differences between the two groups (P > 0.05).
CONCLUSION
Both PVP and TmLRP are effective and safe for the treatment of aged high-risk BPH patients with the prostate heavier than 80 g, but the latter is superior for its shorter operation time and lower surgical cost.
|
pubmed_664_21521
|
pubmed_994_4029
|
The data on the antiviral action of the Ganoderma lucidum, Lentinus edodes, Grifola frondosa, Agaricus brasiliensis and other basidiomycetes metabolites are summurized. The metabolites of these species of basidiomycetes exhibit a direct antiviral effect on herpes simplex virus types I and II, human immunodeficiency virus (HIV), hepatitis B virus, vesicular stomatitis virus, influenza virus, Epstein-Barr virus, and others. Moreover, metabolites of basidiomycetes increased antiviral immunity.
|
pubmed_994_4029
|
pubmed_109_109
|
Fine-needle aspiration biopsy is an established technique for cytodiagnosis of malignant neoplasms, yielding a high rate of positive tissue with negligible local sequelae. The authors report the first instance known to them of needle tract seeding following this biopsy technique in a patient with an unresectable pancreatic carcinoma. Because of the rarity of this occurrence, the procedural indications remain unaltered.
|
10.1148/130.2.345
|
pubmed_529_8856
|
PURPOSE
The management of COPD is a significant and costly issue worldwide, with acute healthcare utilisation consisting of admissions and outpatient attendances being a major contributor to the cost. Pulmonary rehabilitation (PR) and integrated disease management (IDM) are often offered. Whilst there is strong evidence of physical and quality of life outcomes following IDM and PR, few studies have looked into healthcare utilisation. The aims of this study were to confirm whether IDM and PR reduce acute healthcare utilisation and to identify factors which contribute to acute health care utilisation or increased mortality.
METHODS
This was a retrospective cohort study of patients with COPD who were referred to IDM over a 10-year period. Patients were also offered an 8-week PR program. Data collected were matched with the hospital dataset to obtain information on inpatient, ED and outpatient attendances.
RESULTS
517 patients were enrolled to IDM. 315 (61%) also commenced PR and 220 (43%) completed PR. Patients who were referred to PR were younger and had less comorbidities (p < 0.001). Both groups (IDM only and IDM + PR referred) had reductions in healthcare utilisation but the IDM-only group had greater reductions. A survival benefit (HR 0.68, 95% CI 0.50-0.92) was seen in those who were PR completers compared to patients who received IDM only.
CONCLUSIONS
Patients with COPD who successfully complete PR in addition to participating in IDM have improved survival. IDM alone was effective in the reduction of healthcare utilisation; however, the addition of PR did not reduce healthcare usage further.
|
10.1007/s00408-017-0010-9
|
pubmed_563_416
|
This paper uses a large scale and nationally representative dataset, Chinese General Social Survey, to empirically examine the role of physical activity in reducing the negative effects of depression among people with mental disorders. Empirical results demonstrate that physical exercise could help to alleviate depression's adverse consequences on work and life for depressed individuals. The impact mechanism is that physical activity may decrease the severity of depression, enhance life satisfaction, improve mood, and make people have a better sense of purpose and meaning in life. Therefore, from the perspective of multidimensional subjective wellbeing, evaluative wellbeing, experienced wellbeing and eudaimonic wellbeing all play mediating roles in the reduction of depression's adverse effects. Heterogeneity analysis shows that there are no significant gender differences in the health benefits of physical exercise, but its impact tends to be more prominent for depressed individuals who are younger and higher educated, with better health status, and live in urban areas. It is also found that socioeconomic status may play an important moderating role. The health benefits of physical activity seem to be greater for depressed people who have lower income, work in the secondary labor market, and have lower levels of social capital and assets. In addition, the instrumental variable approach is used to identify the causal impact of physical activity, which further proves a significant effect of it based on tackling the endogeneity problem. Meanwhile, this paper uses different explanatory and explained variables, different statistical models, as well as machine learning and placebo techniques to conduct robustness tests, all of which lend credence to above findings.
|
10.3389/fpsyt.2022.1050208
|
pubmed_908_22949
|
OBJECTIVES
This study sought to assess the clinical efficacy, safety, and clinical utility of a novel electroanatomical mapping system.
BACKGROUND
A new mapping system capable of rapidly acquiring detailed maps based on automatic annotation of thousands of points was recently released for clinical use. This is the first description of its utility in humans.
METHODS
The first consecutive 20 cases (7 atrial tachycardia, 8 atrial fibrillation, 3 ventricular tachycardia, and 2 ventricular ectopic beat ablations) were analyzed. The system uses a bidirectional deflectable basket catheter with 64 closely spaced mini-electrodes. It automatically accepts and annotates electrograms when a number of predefined criteria are met.
RESULTS
Thirty right atrial maps were acquired in 11 (4 to 15) min, consisting of 7,220 (3,467 to 10,947) points, 22 left atrial maps in 11 (6 to 19) min, consisting of 7,818 (4,379 to 12,262) points and 10 left ventricular maps in 37 (14 to 43) min, consisting of 8,709 (2,605 to 15,514) points. The mini-basket catheter could reach all areas of interest without deflectable sheaths. No embolic events, bleeding complications, or endocardial structure damage were observed. Correction of the automatic annotation was performed in 0.02% of points in 4 of 62 maps. The system revealed re-entry circuits of atrial tachyarrhythmias, identified gaps on linear lesions, and identified and correctly annotated the clinical ventricular ectopic beats and channels of slow conduction within ventricular scar.
CONCLUSIONS
The novel automatic mapping system was rapid, safe, and efficacious in mapping a variety of cardiac arrhythmias in humans. Further clinical research is needed to optimize its use in the ablation of complex arrhythmias.
|
10.1016/j.jacep.2015.06.002
|
pubmed_1_21908
|
Phylogenetic analysis of highly pathogenic avian influenza A(H5N8) virus strains causing outbreaks in Dutch poultry farms in 2014 provides evidence for separate introduction of the virus in four outbreaks in farms located 16-112 km from each other and for between-farm transmission between the third and fourth outbreak in farms located 550 m from each other. In addition, the analysis showed that all European and two Japanese H5N8 virus strains are very closely related and seem to originate from a calculated common ancestor, which arose between July and September 2014. Our findings suggest that the Dutch outbreak virus strain 'Ter Aar' and the first German outbreak strain from 2014 shared a common ancestor. In addition, the data indicate that the Dutch outbreak viruses descended from an H5N8 virus that circulated around 2009 in Asia, possibly China, and subsequently spread to South Korea and Japan and finally also to Europe. Evolution of the virus seemed to follow a parallel track in Japan and Europe, which supports the hypothesis that H5N8 virus was exchanged between migratory wild waterfowl at their breeding grounds in Siberia and from there was carried by migrating waterfowl to Europe.
|
pubmed_1_21908
|
pubmed_154_9267
|
Gynecologic metastasis of breast carcinoma is not an infrequent event, but metastases within another tumor is very rare. We report a case of unilateral ovarian tumor arising in a 63-year-old woman receiving tamoxifen therapy with a past history of breast carcinoma. The microscopic appearance was principally that of a granulosa cell tumor, but the presence of atypical cells closely admixed within the classical areas was reminiscent of metastasis from breast carcinoma. The diagnosis of this first reported case of breast carcinoma metastasis within granulosa cell tumor was supported by immunohistologic analysis. The diagnosis of tumor-to-tumor metastasis was also confirmed by molecular study using microdissections of samples from the initial breast tumor and from the subsequent ovarian tumor. When compared with normal tissue, carcinomatous cells in the breast tissue exhibited genomic abnormality at the same locus as the metastatic cells in the ovary. In contrast, granulosa cell tumor areas did not show any loss of heterozygosity or instability for the microsatellites analyzed.
|
10.1053/hupa.2002.124038
|
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