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pubmed_906_2088 | PURPOSE
With the mean lung dose (MLD) as an estimator for the normal tissue complication probability (NTCP) of the lung, we assessed whether the probability of tumor control of lung tumors might be increased by dose escalation in combination with a reduction of field sizes, thus increasing target dose inhomogeneity while maintaining a constant MLD.
METHODS AND MATERIALS
An 8-MV AP-PA irradiation of a lung tumor, located in a cylindrically symmetric lung-equivalent phantom, was modeled using numerical simulation. Movement of the clinical target volume (CTV) due to patient breathing and setup errors was simulated. The probability of tumor control, expressed as the equivalent uniform dose (EUD) of the CTV, was assessed as a function of field size, under the constraint of a constant MLD. The approach was tested for a treatment of a non-small cell lung cancer (NSCLC) patient using the beam directions of the clinically applied treatment plan.
RESULTS
In the phantom simulation it was shown that by choosing field sizes that ensured a minimum dose of 95% in the CTV ("conventional" plan) taking into account setup errors and tumor motion, an EUD of the CTV of 43.8 Gy can be obtained for a prescribed dose of 44.2 Gy. By reducing the field size and thus shifting the 95% isodose surface inwards, the EUD increases to a maximum of 68.3 Gy with a minimum dose in the CTV of 55.2 Gy. This increase in EUD is caused by the fact that field size reduction enables escalation of the prescribed dose while maintaining a constant MLD. Further reduction of the field size results in decrease of the EUD because the minimum dose in the CTV becomes so low that it has a predominant effect on the EUD, despite further escalation of the prescribed dose. For the NSCLC patient, the EUD could be increased from an initial 62.2 Gy for the conventional plan, to 83.2 Gy at maximum. In this maximum, the prescribed dose is 88.1 Gy, and the minimum dose in the CTV is 67.4 Gy. In this case, the 95% isodose surface is conformed closely to the "static" CTV during treatment planning.
CONCLUSIONS
Iso-NTCP escalation of the probability of tumor control is possible for lung tumors by reducing field sizes and allowing a larger dose inhomogeneity in the CTV. Optimum field sizes can be derived, having the highest EUD and highest minimum dose in the CTV under condition of a constant NTCP of the lungs. We conclude that the concept of homogeneous dose in the target volume is not the best approach to reach the highest probability of tumor control for lung tumors. | 10.1016/s0360-3016(01)01729-1 |
pubmed_22_1421 | It is estimated that one third of the world's population have latent tuberculosis infection and that this is a significant reservoir for future tuberculosis cases. Most cases occur within two years following initial infection. The identification of individuals with latent tuberculosis infection is difficult due to the lack of an ideal diagnostic assay and incomplete understanding of latent infection. Currently, there are three tests: the oldest tuberculin skin test, T-SPOT.TB and the latest QuantiFERON-Plus for the detection of Mycobacterium tuberculosis infection. The interpretation of the test results must be used in the conjunction with a patient's epidemiological history, risk assessment, current clinical status, radiography and microbiological methods to ensure accurate diagnosis. | 10.5604/17331331.1234987 |
pubmed_924_15403 | Collecting data for the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) ORYX Core Measurement Reporting can be automated using an object-oriented, client-developed program that extracts data from a clinical data repository and utilizes an MHA vendor upload process. The process eliminated 39% of the manual data collection efforts. | pubmed_924_15403 |
pubmed_753_21805 | Ubiquitin-mediated protein degradation is necessary for both increased ventricular mass and survival signaling for compensated hypertrophy in pressure-overloaded (PO) myocardium. Another molecular keystone involved in the hypertrophic growth process is the mammalian target of rapamycin (mTOR), which forms two distinct functional complexes: mTORC1 that activates p70S6 kinase-1 to enhance protein synthesis and mTORC2 that activates Akt to promote cell survival. Independent studies in animal models show that rapamycin treatment that alters mTOR complexes also reduces hypertrophic growth and increases lifespan by an unknown mechanism. We tested whether the ubiquitin-mediated regulation of growth and survival in hypertrophic myocardium is linked to the mTOR pathway. For in vivo studies, right ventricle PO in rats was conducted by pulmonary artery banding; the normally loaded left ventricle served as an internal control. Rapamycin (0.75 mg/kg per day) or vehicle alone was administered intraperitoneally for 3 days or 2 wk. Immunoblot and immunofluorescence imaging showed that the level of ubiquitylated proteins in cardiomyocytes that increased following 48 h of PO was enhanced by rapamycin. Rapamycin pretreatment also significantly increased PO-induced Akt phosphorylation at S473, a finding confirmed in cardiomyocytes in vitro to be downstream of mTORC2. Analysis of prosurvival signaling in vivo showed that rapamycin increased PO-induced degradation of phosphorylated inhibitor of κB, enhanced expression of cellular inhibitor of apoptosis protein 1, and decreased active caspase-3. Long-term rapamycin treatment in 2-wk PO myocardium blunted hypertrophy, improved contractile function, and reduced caspase-3 and calpain activation. These data indicate potential cardioprotective benefits of rapamycin in PO hypertrophy. | 10.1152/ajpheart.00545.2010 |
pubmed_388_2804 | A case of multiple joint and tendon involvement by PVS seems not to have been preciously reported. In a 7-year-old girl there were other organ system problems usually not seen with PVS, and the entire complex may represent a more generalized disease process. The diffuse form of the disease was refractory to multiple attempts at surgical excision. The similarities between PVS and synovial hemangioma suggest that it is important to establish the diagnosis after the first operation. | pubmed_388_2804 |
pubmed_410_5380 | The intrinsic biophysical states of neutrophils are associated with immune dysfunctions in diseases. While advanced image-based biophysical flow cytometers can probe cell deformability at high throughput, it is nontrivial to couple different sensing modalities (e.g., electrical) to measure other critical cell attributes including cell viability and membrane integrity. Herein, an "optics-free" impedance-deformability cytometer for multiparametric single cell mechanophenotyping is reported. The microfluidic platform integrates hydrodynamic cell pinching, and multifrequency impedance quantification of cell size, deformability, and membrane impedance (indicative of cell viability and activation). A newly-defined "electrical deformability index" is validated by numerical simulations, and shows strong correlations with the optical cell deformability index of HL-60 experimentally. Human neutrophils treated with various biochemical stimul are further profiled, and distinct differences in multimodal impedance signatures and UMAP analysis are observed. Overall, the integrated cytometer enables label-free cell profiling at throughput of >1000 cells min-1 without any antibodies labeling to facilitate clinical diagnostics. | 10.1002/smll.202104822 |
pubmed_1086_10739 | Various isotope coding strategies are being used today in the field of comparative proteomics. This article specifically reviews the strengths and limitations of various N-termini-directing strategies. N-termini-directed coding strategy allows for use of different chromatographic enrichment techniques. Since N-termini-directed coding strategies are global in nature, they can be utilized in studying PTMs as well as protein expression. Using different N-termini-directed coding strategies, both relative and absolute quantification of proteins can be achieved either in the MS mode or in the MS/MS mode. The review ends with the conclusion that significant improvements have been made in the last decade. Among various issues, a need still exists for a better understanding of the kinetic issues in proteomics, relative protein pool sizes for different proteins and the issue of stimulus-induced changes in protein aggregation. Another critical issue that needs to be addressed in great detail is the role of PTMs in regulation. | 10.1002/pmic.200500553 |
pubmed_621_24773 | In vivo angiogenesis assays provide more physiologically relevant information about tumor vascularization than in vitro studies because they take the complex interactions among cancer cells, endothelial cells, mural cells, and tumor stroma into consideration. Traditional microscopic assessment of vascular density conducted by immunostaining of tissue sections or by lectin angiogram visualization of tumor vessels is invasive and requires the sacrifice of tumor-bearing animals. Therefore, it prohibits longitudinal time-course observation in a single animal and requires a large number of animals at each time point to derive statistically-meaningful observations. Additionally, heterogenous behavior among different tumors will inevitably introduce individual biological variance that may obscure reliable interpretation of the results. While various artificial in vivo angiogenesis assays, such as the Matrigel implant assay, chick chorioallatoic membrane assay, and dorsal skin fold chamber assay have been developed and employed to more directly observe the progression of physiological angiogenesis, they can not appropriately assess tumor angiogenic progression or tumor vascular regression in response to therapeutic intervention. Here, we describe a noninvasive method and a detailed protocol that we have developed and optimized using the Olympus OV-100 in vivo imaging system for real-time high-resolution visualization and assessment of tumor angiogenesis and vascular response to anticancer therapies in live animals. We show that using this approach, tumor vessels can be monitored longitudinally through the whole vasculogenesis and angiogenesis process in the same mouse. Further, morphologic changes of the same vessel prior to and after drug treatments can be captured with microscopic high resolution. Moreover, the multichannel co-imaging capability of the OV-100 allows us to analyze and compare tumor vessel permeability before and after antiangiogenesis therapy by employing a near-infrared blood pool reagent, or by visualizing improved cytotoxic drug delivery upon tumor vessel normalization by using a fluorophore tagged drug. This noninvasive method can be readily applied to orthotopically transplanted breast cancer models as well as to subcutaneously-transplanted tumor models. | 10.1007/978-1-61779-797-2_8 |
pubmed_598_16696 | Patients with thick skin typically present with a redundant, baggy, lax skin envelope together with prominent nasolabial folds, jowls, and a heavy neck. Durable and natural-appearing rejuvenation is not possible unless the deformities are addressed adequately and harmoniously in these patients. Traditional superficial musculoaponeurotic system techniques do not include surgical release of the zygomatic cutaneous ligaments and repositioning of descendent malar fat pad, and may lead to an unbalanced, unnatural appearance and the lateral sweep phenomenon. Additional attempts to improve unopposed nasolabial folds such as fat grafting to malar region are more likely to result with a "stuffed" look, far from a natural and rejuvenated appearance, and must therefore be avoided. The facelift techniques including true release of the anchoring ligaments of the midface and allowing adequate repositioning of saggy tissues are ideal for these patients to obtain harmonious, natural result. Despite the extensive dissections, maximal release, and maximal lateral pull, additional maneuvers, e.g., platysmaplasty, subplatysmal fat removal, or partial resection of submandibular glands may be required for satisfying result in patients with heavy neck. In this article, the authors outline the relevant anatomy of the facial retaining ligaments and their implications to surgical management of patients with heavy skin are discussed. | 10.1055/s-0037-1615283 |
pubmed_361_23165 | As part of a series of articles on various aspects of image conservation, practical advice is given on how best to ensure image permanence of contemporary photographs. | 10.3109/17453058909055086 |
pubmed_1020_14799 | BACKGROUND
Protein phosphatase 2A (PP2A, a serine/threonine phosphatase) is frequently inactivated in many types of cancer, including primary liver cancer (PLC). Genetic variations in PP2A subunits have been reported to be associated with the risk of many types of cancer but rarely in PLC. This study aims to assess the association between functional polymorphisms of PP2A subunit genes and the risk of PLC in Chinese.
METHODS
In a case-control study with a total of 541 PLC patients and 547 controls in Guangxi province of Southern China, we genotyped six putatively functional polymorphisms (rs10421191G>A, rs11453459del>insG, rs1560092T>G, rs7840855C>T, rs1255722G>A and rs10151527A>C) of three PP2A subunit genes (PPP2R1A, PPP2R2A and PPP2R5E) using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry platform.
RESULTS
The rs11453459insG variant genotypes (ins/ins+del/ins) of PPP2R1A were found to be significantly associated with an increased risk of PLC compared with the del/del genotype (adjusted OR = 1.290, 95% CI = 1.009-1.650), and the number of insert G allele worked in a dose-dependent manner (P trend= 0.007). The stratified analysis showed that the effects of rs11453459insG variant genotypes were more evident in the subgroup who drink pond-ditch water (adjusted OR = 3.051, 95% CI = 1.264-7.364) than those never drink (P = 0.041). The carriers of rs11453459 del/ins genotype had a significantly lower level of PPP2R1A mRNA expression in liver cancer tissues than those of the del/del genotype (P = 0.021). Furthermore, we used microcystin-LR, a carcinogen presents in the pond-ditch water, to treat human peripheral blood mononuclear cells and found that the cells from carriers of rs11453459insG variant genotypes induced more DNA oxidative damages than those from the del/del genotype carriers (P < 0.001).
CONCLUSION
These findings suggest that the PPP2R1A rs11453459del>insG polymorphism is associated with an increased risk of PLC, especially for persons with a history of drinking pond-ditch water. This insertion/deletion polymorphism may be a susceptible biomarker for PLC in Chinese. | 10.2147/PGPM.S335555 |
pubmed_354_25412 | A simple, rapid, and efficient liquid chromatography tandem mass spectrometry (LC-MS/MS) method, operated in electrospray ionization and quadrupole linear ion trap modes, has been developed for the identification and structural characterization of aflatoxins in peanuts and its derivative products or bean sauce. Samples (5 g) were extracted with acetonitrile/water/formic acid (79:20:1, v/v). After centrifugation and dilution, the extracts were separated on a C18 analytical column by gradient elution (acetonitrile/0.2% formic acid) and analyzed by UPLC-MS/MS. External calibration was used for qualification. The developed multiple reaction monitoring-information-dependent acquisition-enhanced product ion method enabled quantification and confirmation of the analytes in a single run. Enhanced product ion mode was used for qualitative analysis, while multiple reaction monitoring mode was used for quantitative analysis. An in-house library was constructed for identification. Calibration curves showed good linearity with correlation coefficients (r) higher than 0.994. Limits of detection were determined to be below 0.26 µg kg-1 for most analytes. The recoveries for those substances were in the acceptable range of 80.2%-119.1%. A new LC-MS3 method was established for further confirmation. One pickled pepper peanut was found to contain aflatoxins B1, B2, and G1 with contents of 90.93, 26.64, and 1.92 µg kg-1, respectively. | 10.1177/1469066719866050 |
pubmed_351_5113 | A report is given on a rare case of nongestational primary chorionepithelioma of the ovary. A 30 years old woman was treated by salpingo-oophorectomy and methotrexate-monotherapy. She is showing long-term remission. | pubmed_351_5113 |
pubmed_559_9742 | The contribution of mitochondria to the manifestation of disease is ascribed largely to the production of reactive oxygen species (ROS), which are obligatory by-products of aerobiosis. Studies using isolated mitochondria have revealed multiple potential sites and circumstances of ROS production but the relevance of these to in situ conditions is limited. In this article, we focus on bioenergetic factors that promote ROS generation at physiologically relevant sites in mitochondria. Emphasis is given to ROS generation by complex I--the first component of the respiratory chain--and to how the NADH:NAD+ ratio regulates ROS formation. Complex I is a physiologically and pathologically relevant ROS-forming site that is important not only in normal mitochondrial energy production but also in the pathogenesis of Parkinson's disease, which is the second most common neurodegenerative disease. | 10.1016/j.tips.2006.10.005 |
pubmed_1046_3721 | Despite causing permanent hearing loss by damaging inner ear sensory cells, aminoglycosides (AGs) remain one of the most widely used classes of antibiotics in the world. Although the mechanisms of cochlear sensory cell damage are not fully known, reactive oxygen species (ROS) are clearly implicated. Mitochondrial-specific ROS formation was evaluated in acutely cultured murine cochlear explants exposed to gentamicin (GM), a representative ototoxic AG antibiotic. Superoxide (O2·-) and hydrogen peroxide (H2O2) were measured using MitoSOX Red and Dihydrorhodamine 123, respectively, in sensory and supporting cells. A 1-h GM exposure significantly increased O2·- formation in IHCs and increased H2O2 formation in all cell types. At the same time point, GM significantly increased manganese superoxide dismutase (MnSOD) levels while significantly decreasing copper/zinc superoxide dismutase (CuZnSOD) in cochlear sensory cells. This suggests (1) a rapid conversion of highly reactive O2·- to H2O2 during the acute stage of ototoxic antibiotic exposure and (2) that the endogenous antioxidant system is significantly altered by AGs. Fluorescence intensity-based measurements of reduced nicotinamide adenine dinucleotide (phosphate) [NAD(P)H] and mitochondrial membrane potential were measured to determine if increases in GM-induced ROS production were correlated with changes in mitochondrial metabolism. This project provides a basis for understanding the mechanisms of mitochondrial ROS production in cochlear cells exposed to ototoxic antibiotics. Understanding the nature of ototoxic antibiotic-induced changes in mitochondrial metabolism is critical for developing hearing loss treatment and prevention strategies. | 10.1117/1.JBO.24.5.051403 |
pubmed_433_4074 | OBJECTIVE
Students from regional and remote backgrounds are more likely to stay and work in regional and remote locations. Health students transition and retention at university impacts the retainment of a competent rural health workforce. This study aimed to examine the perceptions of allied health students as they reflected upon their first six weeks at university and identified strategies which enhanced these experiences.
DESIGN
A cross-sectional study. Surveys were administered to students who then completed a reflection exercise. Data were analysed using Pearson correlation coefficient and chi-squares.
SETTING
An Australian regional university.
PARTICIPANTS
First year occupational therapy, physiotherapy and speech pathology students.
MAIN OUTCOME MEASURES
Factors influencing the first 6 weeks at university.
RESULTS
One hundred and forty-three students participated. Homesickness was the major challenge in transitioning to university life. Subthemes identified were adjusting to being away from home, adjusting to university culture and the mature-aged student. Specific issues included a lack of familiarity with university campuses and services, being unprepared for the workload and confusion while learning new skills.
CONCLUSION
Orientation week activities assist students transition into university and age-appropriate and family-friendly activities should be considered for mature-age students. All students were found to benefit from support to address economic pressures and skill development focusing on coping with university workload. The development of regional university policy including these strategies is likely to enhance student success. | 10.1111/ajr.12581 |
pubmed_474_2315 | An account is given of a study, carried out in a Cambridge suburb, which measured the similarity in IQ and some personality traits between spouses. In both sexes mean IQ scores tended to diminish from social class I to V. Lower IQ scores were associated with higher levels of extraversion, neuroticism and inconsistency. Assortative marriage was found for IQ components, Total IQ, extraversion-introversion and inconsistency scores. Both geographical and social stratification were shown to affect the degree of assortative marriage. | 10.1080/03014467900003321 |
pubmed_228_23280 | Mixed CH(4)/CF(4) clusters as well as pure clusters of CF(4) were produced by adiabatic expansion and studied by carbon 1s (C1s) X-ray photoelectron spectroscopy. Evidence is presented that CH(4) and CF(4) do indeed form binary clusters in CH(4)/CF(4) coexpansion experiments and that these clusters exhibit radial structure; i.e., CF(4) is primarily found in the bulk. The interpretation of the photoelectron spectra is supported by calculations of C1s ionization energies based on theoretical clusters models. | 10.1021/jp206332y |
pubmed_678_17726 | Using magnetic resonance imaging (MRI) for guiding minimally invasive interventions requires surgical devices which on one hand are visible in the MR image but on the other hand do not generate large artifacts, which distort the overall imaging process. Passive markers are one way to visualize devices such as catheters or biopsy needles in MRI. The evaluation of newly developed passive markers usually requires access to high-field MRI scanners (1.5 T and 3 T). This makes the practical evaluation time-consuming and expensive. Hence, we propose to use a high-resolution, low field (0.55 T) benchtop MRI system to quantify the size of an artifact and to make a prediction for its corresponding size in a clinical high-field system. For the evaluation of the proposed method, catheters coated with different passive marker materials in varying concentrations were imaged in the 0. 55 T benchtop MRI scanner as well as in clinical 3 T MRI system using FLASH sequences. The experimental results revealed that an artifact prediction based on measurements in the 0. 55 T is possible for the tested marker materials. Hence, the proposed approach has a high potential for testing newly developed medical devices at a low cost, in less time and during the development process for fast feedback. | 10.1109/EMBC.2016.7590933 |
pubmed_1012_3288 | Phenylbutazone (PBZ) was administered to six calves intravenously (i.v.) and orally at a dose rate of 4.4 mg/kg in a three-period cross-over study incorporating a placebo treatment to establish its pharmacokinetic and pharmacodynamic properties. Extravascular distribution was determined by measuring penetration into tissue chamber fluid in the absence of stimulation (transudate) and after stimulation of chamber tissue with the mild irritant carrageenan (exudate). PBZ pharmacokinetics after i.v. dosage was characterized by slow clearance (1.29 mL/kg/h), long-terminal half-life (53.4 h), low distribution volume (0.09 L/kg) and low concentrations in plasma of the metabolite oxyphenbutazone (OPBZ), confirming previously published data for adult cattle. After oral dosage bioavailability (F) was 66%. Passage into exudate was slow and limited, and penetration into transudate was even slower and more limited; area under curve values for plasma, exudate and transudate after i.v. dosage were 3604, 1117 and 766 microg h/mL and corresponding values after oral dosage were 2435, 647 and 486 microg h/mL. These concentrations were approximately 15-20 (plasma) and nine (exudate) times greater than those previously reported in horses (receiving the same dose rate of PBZ). In the horse, the lower concentrations had produced marked inhibition of eicosanoid synthesis and suppressed the inflammatory response. The higher concentrations in calves were insufficient to inhibit significantly exudate prostaglandin E2 (PGE2), leukotriene B4 (LTB4) and beta-glucuronidase concentrations and exudate leucocyte numbers, serum thromboxane B2 (TxB2), and bradykinin-induced skin swelling. These differences from the horse might be the result of: (a) the presence in equine biological fluids of higher concentrations than in calves of the active PBZ metabolite, OPBZ; (b) a greater degree of binding of PBZ to plasma protein in calves; (c) species differences in the sensitivity to PBZ of the cyclo-oxygenase (COX) isoenzymes, COX-1 and COX-2 or; (d) a combination of these factors. To achieve clinical efficacy with single doses of PBZ in calves, higher dosages than 4.4 mg/kg will be probably required. | 10.1046/j.1365-2885.2002.00421.x |
pubmed_612_5048 | BACKGROUND
A new syndrome of vaccine-induced immune thrombotic thrombocytopenia (VITT) has emerged as a rare side-effect of vaccination against COVID-19. Cerebral venous thrombosis is the most common manifestation of this syndrome but, to our knowledge, has not previously been described in detail. We aimed to document the features of post-vaccination cerebral venous thrombosis with and without VITT and to assess whether VITT is associated with poorer outcomes.
METHODS
For this multicentre cohort study, clinicians were asked to submit all cases in which COVID-19 vaccination preceded the onset of cerebral venous thrombosis, regardless of the type of vaccine, interval between vaccine and onset of cerebral venous thrombosis symptoms, or blood test results. We collected clinical characteristics, laboratory results (including the results of tests for anti-platelet factor 4 antibodies where available), and radiological features at hospital admission of patients with cerebral venous thrombosis after vaccination against COVID-19, with no exclusion criteria. We defined cerebral venous thrombosis cases as VITT-associated if the lowest platelet count recorded during admission was below 150 × 109 per L and, if the D-dimer was measured, the highest value recorded was greater than 2000 μg/L. We compared the VITT and non-VITT groups for the proportion of patients who had died or were dependent on others to help them with their activities of daily living (modified Rankin score 3-6) at the end of hospital admission (the primary outcome of the study). The VITT group were also compared with a large cohort of patients with cerebral venous thrombosis described in the International Study on Cerebral Vein and Dural Sinus Thrombosis.
FINDINGS
Between April 1 and May 20, 2021, we received data on 99 patients from collaborators in 43 hospitals across the UK. Four patients were excluded because they did not have definitive evidence of cerebral venous thrombosis on imaging. Of the remaining 95 patients, 70 had VITT and 25 did not. The median age of the VITT group (47 years, IQR 32-55) was lower than in the non-VITT group (57 years; 41-62; p=0·0045). Patients with VITT-associated cerebral venous thrombosis had more intracranial veins thrombosed (median three, IQR 2-4) than non-VITT patients (two, 2-3; p=0·041) and more frequently had extracranial thrombosis (31 [44%] of 70 patients) compared with non-VITT patients (one [4%] of 25 patients; p=0·0003). The primary outcome of death or dependency occurred more frequently in patients with VITT-associated cerebral venous thrombosis (33 [47%] of 70 patients) compared with the non-VITT control group (four [16%] of 25 patients; p=0·0061). This adverse outcome was less frequent in patients with VITT who received non-heparin anticoagulants (18 [36%] of 50 patients) compared with those who did not (15 [75%] of 20 patients; p=0·0031), and in those who received intravenous immunoglobulin (22 [40%] of 55 patients) compared with those who did not (11 [73%] of 15 patients; p=0·022).
INTERPRETATION
Cerebral venous thrombosis is more severe in the context of VITT. Non-heparin anticoagulants and immunoglobulin treatment might improve outcomes of VITT-associated cerebral venous thrombosis. Since existing criteria excluded some patients with otherwise typical VITT-associated cerebral venous thrombosis, we propose new diagnostic criteria that are more appropriate.
FUNDING
None. | 10.1016/S0140-6736(21)01608-1 |
pubmed_1021_17942 | Environmental parameters such as temperature and wind, occupant activities, and house-specific parameters such as subsoil geology, leakiness of the substructure to soil gas, and air exchange rate are the main factors influencing Rn entry into a building and its subsequent indoor behavior. Experiments performed in an unheated, uninhabited house showed a reproducible diurnal fluctuation of the indoor concentration of Rn decay products. Strong, long-term correlations between temperature differences indoor-outdoor (indoor temperature minus outdoor temperature) and pressure differences outdoor-indoor (outdoor pressure minus indoor pressure) were found. At positive temperature differences inside-outside, an average airflow velocity of about 0.05 m s-1 between ground floor and first floor was detected. This air movement was able to vertically transport Rn at a rate of approximately 11 kBq h-1 in a volume of air of about 5.5 m3 through a cross-sectional area of only 0.03 m2. For this specific house, stack effects were identified as the main driving force for Rn migration from the cellular to higher floors. The diurnal fluctuation of Rn progeny concentrations in the living area can be explained by temporal variations in the amount of Rn-rich air transported vertically from the cellar into the building as a consequence of stack effects. | 10.1097/00004032-199103000-00009 |
pubmed_65_1970 | Huntington's disease (HD) is an inherited, autosomal dominant, neurodegenerative disorder characterized by involuntary choreiform movements, cognitive decline and a progressive neuronal degeneration primarily affecting the striatum. There is at present no effective therapy against this disorder. The gene responsible for the disease (IT15) has been cloned and the molecular defect identified as an expanded polyglutamine tract in the N-terminal region of a protein of unknown function, named huntingtin (The Huntington's Disease Collaborative Research Group, 1993. Cell 72, 971-983). An intense, search for the cell pathology attached to this molecular defect is currently under way [see Sharp and Ross (1996, Neurobiol. Dis. 3, 3-15) for review]. Huntingtin interacts with a number of proteins, some of which have well identified functions, and it has thus been suggested that alterations in glycolysis, vesicle trafficking or apoptosis play a role in the physiopathology of HD. On the other hand data derived from positron emission tomography (PET), magnetic resonance spectroscopy and post-mortem biochemical evidence for a defect in succinate oxidation have suggested the implication of a primary impairment of mitochondrial energy metabolism. All these hypotheses are not necessarily to be opposed and recent findings indicate that the HD mutation could possibly directly alter mitochondrial functions which would in turn activate apoptotic pathways. To test this mitochondrial hypothesis, we studied the effects in rodents and non-human primates of a chronic blockade of succinate oxidation by systemic administration of the mitochondrial toxin 3-nitropropionic acid (3NP). Extensive behavioural and neuropathological evaluations showed that a partial but prolonged energy impairment induced by 3NP is sufficient to replicate most of the clinical and pathophysiological hallmarks of HD, including spontaneous choreiform and dystonic movements, frontal-type cognitive deficits, and progressive heterogeneous striatal degeneration at least partially by apoptosis. 3NP produces the preferential degeneration of the medium-sized spiny GABAergic neurons with a relative sparing of interneurons and afferents, as was observed in HD striatum. The present manuscript reviews the different aspects of this neurotoxic treatment in rodents and non-human primates, and its interest as a phenotypic model of HD to understand the degenerative process of HD and test new therapeutic strategies. | 10.1016/s0301-0082(99)00005-2 |
pubmed_642_5908 | Artemisia integrifolia L (Compositae) is a medicinal and edible plant. To investigate its antihyperlipidemic effect, a crude lipophilic extract and the composing compounds were isolated and fractioned from the petroleum ether extract of aerial parts of A. integrifolia using column chromatography on silica gel. The anti-hyperlipidemia effect was studied in a rat model of acute hyperlipidemia, which was induced by triton WR-1339. A new compound, integrinol (4), together with nine known compounds, namely chamazulene (1), acetylenes (E)-2 (2), acetylenes (E)-3 (3), eugenol (5), palmitic acid (6), oleic acid (7), linoleic acid (8), linolenic acid (9) and 12,13-epoxylinolenic acid were isolated from the crude lipophilic extract of A. integrifolia. The LD50 value of the crude extract was more than 4g/kg. In Triton WR-1339-induced acute hyperlipidemia model, the crude lipophilic extract (200 mg/kg) significantly reduced total cholesterol (TC) by 70% (p ≤ 0.01) and triglycerides (TGs) by 94% (p ≤ 0.001). The fractioned compounds, such as chamazulene (1), acetylene-2 (2), and linolenic acid (9), used at 4 mg/kg dose, also significantly decreased the concentrations of TC (32%, 33% and 64%, respectively) and TGs (48%, 33% and 93%, respectively). These compounds (i.e., chamazulene, acetylenes (E)-2, and linolenic acid) were considered to be responsible for the bioactive antihyperlipidemic effect. In conclusion, the crude lipid extract of Artemisia integrifolia L could be used as a potential treatment to avert hyperlipidemia. Further studies to confirm these results in other models of hyperlipidemia (e.g., diet-induced obesity) are warranted. | 10.3390/molecules24040725 |
pubmed_92_19559 | We tested the hypothesis that infusion of ascorbic acid (AA), a potent antioxidant, would alter vasodilator responses to exercise in human obesity and metabolic syndrome (MetSyn). Forearm blood flow (FBF, Doppler ultrasound) was measured in lean, obese, and MetSyn adults (n = 39, 32 ± 2 yr). A brachial artery catheter was inserted for blood pressure monitoring and local infusion of AA. FBF was measured during dynamic handgrip exercise (15% maximal effort) with and without AA infusion. To account for group differences in blood pressure and forearm size, and to assess vasodilation, forearm vascular conductance (FVC = FBF/mean arterial blood pressure/lean forearm mass) was calculated. We examined the time to achieve steady-state FVC (mean response time, MRT) and the rise in FVC from rest to steady-state exercise (Δ, exercise - rest) before and during acute AA infusion. The MRT (P = 0.26) and steady-state vasodilator responses to exercise (ΔFVC, P = 0.31) were not different between groups. Intra-arterial infusion of AA resulted in a significant increase in plasma total antioxidant capacity (174 ± 37%). AA infusion did not alter MRT or steady-state FVC in any group (P = 0.90 and P = 0.85, respectively). Interestingly, higher levels of C-reactive protein predicted longer MRT (r = 0.52, P < 0.01) and a greater reduction in MRT with AA infusion (r = -0.43, P = 0.02). We concluded that AA infusion during moderate-intensity, rhythmic forearm exercise does not alter the time course or magnitude of exercise-mediated vasodilation in groups of young lean, obese, or MetSyn adults. However, systemic inflammation may limit the MRT to exercise, which can be improved with AA. | 10.1152/ajpheart.00312.2014 |
pubmed_596_11634 | OBJECTIVES
Constipation can adversely affect children's health, with disorders of host immunity and enhanced oxidative stress. As nondigestible carbohydrates, prebiotics can affect the host with constipation; however, whether the prebiotics have effects on the content of intestinal secretory immunoglobulin A (sIgA) and the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in constipation has not been fully clarified.
METHODS
In the present study, constipation was induced in female Sprague-Dawley rats by diphenoxylate, and the prebiotics dissolved in milk were used as an intervention. The indicators of intestinal peristalsis, including the time of passing black stool initially, the grains of black stool in 24 hours, and the advance rate of ponceau, were measured. The content of intestinal sIgA was detected by enzyme-linked immunosorbent assay. The contents of SOD and MDA in serum and intestinal tissue were analyzed by their detection kits.
RESULTS
The changes in intestinal peristalsis show obvious constipation. The content of intestinal sIgA decreases, the content of SOD decreases, but the content of MDA increases in constipated rats. Prebiotics can attenuate the constipation-caused abnormal indicators significantly.
CONCLUSIONS
Prebiotics can attenuate decreased intestinal immunity and enhanced oxidative stress, in addition to reduced intestinal peristalsis and of the constipated rats. | 10.1097/MPG.0b013e31821eed83 |
pubmed_283_7245 | As a continuation of our studies on structure-activity relationship of vitamin D compounds we synthesized new calcitriol analogs characterized by the presence of an exomethylene substituent at C-2. The A-ring dienyne synthon was prepared from commercially available quinic acid by two different synthetic routes, and it was then coupled with the triflate enol derived from the corresponding (20R)- and (20S)-Grundmann ketone by palladium catalyzed Sonogashira reaction. The obtained 1α,25-dihydroxy-2-methylene-vitamin D3 analogs, epimeric at C-20, were biologically evaluated by in vitro and in vivo studies. Both isomers exhibited unique activity profiles and greater biological potency than 1α,25-(OH)2D3. It was established that the biological profiles of the newly obtained vitamin D compounds depend on the configuration at C-20. Thus, introduction of 2-methylene substituent to the calcitriol molecule together with alteration of stereochemistry of its side chain induces remarkable changes in a VDR-mediated signaling response and enhances biological activity. This article is part of a Special Issue entitled 'Vitamin D Workshop'. | pubmed_283_7245 |
pubmed_351_19235 | Severed halves of medial giant axons (MGAs) and lateral giant axons (LGAs) in earthworms survive and are functionally reconnected as early as the first postoperative week. During the first 150 postoperative days, there is an increase in conduction velocity of action potentials and strength of electrotonic coupling between the severed axonal stumps across the lesion site. Electrophysiological analyses suggest that this functional reconnection occurs by transmission of action potentials through the lesion site by active propagation along neurites which make electrotonic connections rather than chemical synapses. The regenerated connections restore the original connectivity pattern for conduction of action potentials or spread of electrotonic potentials; i.e., MGA stumps reconnect with MGA stumps, and LGA stumps with LGA stumps. These and other data suggest that the mechanisms responsible for establishing appropriate functional reconnection of severed earthworm giant axons requires cell-specific matching of axons and neurites, rather than a competition between appropriate and inappropriate functional connections. | 10.1016/0014-4886(92)90139-h |
pubmed_944_22320 | OBJECTIVE
to explore the experience of giving birth for first-time New Zealand mothers.
DESIGN
qualitative methodology was employed to obtain an in-depth insight into the birth experience using semi-structured interviews conducted face-to-face 11 days to 16 weeks (median 13.5 weeks) after giving birth were audio-recorded and transcribed verbatim.
SETTING
the interviews were of a small group of New Zealand mothers.
PARTICIPANTS
ten first-time mothers aged 24-38 years (median 31.5 years) participated.
MEASUREMENTS
transcripts were analysed using a phenomenological form of thematic analysis.
FINDINGS
a core theme was relationship issues. Two subthemes were delineated: lack of relationship between mothers and midwives and doctors; and the conflict between midwives and doctors.
KEY CONCLUSIONS
personal, caring and co-operative relationships with all maternity care professionals were basic to New Zealand mothers feeling good about their birth experience.
IMPLICATIONS FOR PRACTISE
relationships, with and between, all maternity care professionals merit further investigation in an effort to optimise birth satisfaction. | 10.1016/j.midw.2011.07.004 |
pubmed_561_17432 | Among human bicarbonate transporters, two major gene families encode Na-independent Cl(-)/HCO(3)(-) exchangers: the SLC4 anion exchanger (AE) family, and the SLC26 "sulfate permease" anion transporter family. The SLC4 AE family contains at least three genes, and comprises a subfamily within the larger and phylogenetically more ancient bicarbonate transporter superfamily that includes the Na bicarbonate cotransporters (NBC) and the Na-driven Cl/base exchangers. Mutations in the human AE1 gene cause autosomal dominant spherocytic anemia and distal renal tubular acidosis of both dominant and recessive forms. Anemia is also associated with AE1 mutations in mouse, cow, and zebrafish. Naturally occurring mutations in the human AE2 and AE3 genes have not been detected. The SLC26 family in humans consists of at least 10 members, and includes anion exchangers which exchange chloride for bicarbonate, hydroxyl, sulfate, formate, iodide, and/or oxalate. Mutations in three of these genes cause hereditary disease, including chondrodysplasia (SLC26A2, DTD), diarrhea (A3, down-regulated in adenoma/chloride-losing diarrhea protein: DRA/CLD), and goiter/deafness syndrome (A4, pendrin). Little is known about the acute regulation of these modulators of intracellular and compartmental pH and volume. | pubmed_561_17432 |
pubmed_629_11897 | This article seeks to provide commentary and rationale for Orthodox Christian rites and prayers for the sick as found in the Euchologion, or Book of Needs. The reader needs to understand that the prayers of the Orthodox Church prayed at times of sickness and suffering will often strike the non-Orthodox as harsh and even unjust. References to God willing suffering do not sit well with most Western Christians. However, this is the Orthodox Christian belief, and it is expressed in the prayers of the Orthodox Church. Sickness and suffering are understood to be avenues of salvation and a participation in the glory and joys of the resurrection of Christ and life in the Kingdom of God. This is why the Orthodox Church teaches her faithful to accept suffering as something that has the potential to bring them further along in the process of theosis. | 10.1080/13803600600805583 |
pubmed_295_12829 | Background: Facilitating access to health data for public health and research purposes is an important element in the health policy agenda of many countries. Improvements in this sense can only be achieved with the development of an appropriate data infrastructure and the implementations of policies that also respect societal preferences. Switzerland is a revealing example of a country that has been struggling to achieve this aim. The objective of the study is to reflect on stakeholders' recommendations on how to improve the health data framework of this country. Methods: We analysed the recommendations collected as part of a qualitative study including 48 expert stakeholders from Switzerland that have been working principally with health databases. Recommendations were divided in themes and subthemes according to applied thematic analysis. Results: Stakeholders recommended several potential improvements of the health data framework in Switzerland. At the general level of mind-set and attitude, they suggested to foster the development of an explicit health data strategy, better communication and the respect of societal preferences. In terms of infrastructure, there were calls for the creation of a national data center, the improvement of IT solutions and the use of a Unique Identifier for patient data. Lastly, they recommended harmonising procedures for data access and to clarify data protection and consent rules. Conclusion: Recommendations show several potential improvements of the health data framework, but they have to be reconciled with existing policies, infrastructures and ethico-legal limitations. Achieving a gradual implementation of the recommended solutions is the preferable way forward for Switzerland and a lesson for other countries that are also seeking to improve health data access for public health and research purposes. | 10.3389/fpubh.2021.668386 |
pubmed_341_21346 | INTRODUCTION
Mass spectrometry and computational biology have advanced significantly in the past ten years, bringing the field of metabolomics a step closer to personalized medicine applications. Despite these analytical advancements, collection of blood samples for routine clinical analysis is still performed through traditional blood draws.
OBJECTIVE
TAP capillary blood collection has been recently introduced for the rapid, painless draw of small volumes of blood (~ 100 μL), though little is known about the comparability of metabolic phenotypes of blood drawn via traditional venipuncture and TAP devices.
METHODS
UHPLC-MS-targeted metabolomics analyses were performed on blood drawn traditionally or through TAP devices from 5 healthy volunteers. Absolute quantitation of 45 clinically-relevant metabolites was calculated against stable heavy isotope-labeled internal standards.
RESULTS
Ranges for 39 out of 45 quantified metabolites overlapped between drawing methods. Pyruvate and succinate were over threefold higher in the TAP samples than in traditional blood draws. No significant changes were observed for other carboxylates, glucose or lactate. TAP samples were characterized by increases in reduced glutathione and decreases in urate and cystine, markers of oxidation of purines and cysteine-overall suggesting decreased oxidation during draws. The absolute levels of bile acids and acyl-carnitines, as well as almost all amino acids, perfectly correlated among groups (Spearman r ≥ 0.95).
CONCLUSION
Though further more extensive studies will be mandatory, this pilot suggests that TAP-derived blood may be a logistically-friendly source of blood for large scale metabolomics studies-especially those addressing amino acids, glycemia and lactatemia as well as bile acids, acyl-carnitine levels. | 10.1007/s11306-018-1395-z |
pubmed_944_2192 | Sponges are sessile filter feeders that, among the metazoans, evolved first on Earth. In the two classes of the siliceous sponges (the Demospongiae and the Hexactinellida), the complex filigreed body is stabilized by an inorganic skeleton composed of amorphous silica providing them a distinct body shape and plan. It is proposed that the key innovation that allowed the earliest metazoans to form larger specimens was the enzyme silicatein. This enzyme is crucial for the formation of the siliceous skeleton. The first sponge fossils with body preservation were dated back prior to the "Precambrian-Cambrian" boundary [Vendian (610-545 Ma)/Ediacaran (542-580 Ma)]. A further molecule required for the formation of a hard skeleton was collagen, fibrous organic filaments that need oxygen for their formation. Silicatein forming the spicules and collagen shaping their morphology are the two organic components that control the appositional growth of these skeletal elements. This process starts in both demosponges and hexactinellids intracellularly and is completed extracellularly where the spicules may reach sizes of up to 3 m. While the basic strategy of their formation is identical in both sponge classes, it differs on a substructural level. In Hexactinellida, the initial silica layers remain separated, those layers bio-fuse (bio-sinter) together in demosponges. In some sponge taxa, e.g., the freshwater sponges from the Lake Baikal, the individual spicules are embedded in an organic matrix that is composed of the DUF protein. This protein comprises clustered stretches of amino acid sequences composed of pronounced hydrophobic segments, each spanning around 35 aa. We concluded with the remark of Thompson (1942) highlighting that "the sponge-spicule is a typical illustration of the theory of 'bio-crystallisation' to form 'biocrystals' ein Mittelding between an inorganic crystal and an organic secretion." Moreover, the understanding of the enzymatic formation of the spicules conferred sponge biosilica a considerable economical actuality as a prime raw material of this millennium. | 10.1007/978-3-642-21230-7_9 |
pubmed_359_21720 | In 927 biologically unrelated Caucasian patients with coronary artery disease it was investigated whether the NcoI restriction fragment length polymorphism of the muscle-specific creatine kinase (CKMM) gene is associated with aerobic power and with the response to physical training. Physical training significantly (P<0.001) increased peak oxygen consumption in the GG, AG and AA NcoI genotypes. Covariate-adjusted peak oxygen consumption at baseline, after training and the response to training were not different across CKMM NcoI genotypes. | 10.1097/01.hjr.0000170266.30562.59 |
pubmed_56_11803 | BACKGROUND
Facet joint pain is a common cause of low back pain. There are no physical exam findings that provide a reliable diagnosis. Diagnosis is made by medial branch block injections (MBB). Once the source of pain has been determined, radiofrequency neurotomy (RFN) can be performed. Previous studies have shown that RFN reduces level of pain and improves function. No study has tried to correlate MBB results with outcomes after RFN.
OBJECTIVES
(1) Estimate percentage decrease in pain, decrease in analgesic use, and increase in activity tolerance after facet joint radiofrequency neurotomy (2) Determine correlation between percentage pain relief or duration of pain relief after MBB and RFN outcomes.
STUDY DESIGN
Retrospective review of patients undergoing RFN, who had = 70% pain relief on 2 sets of MBB with 0.5 - 1 mL of 2% lidocaine (MBB 1) and 0.75% bupivacaine (MBB 2). IRB approval was obtained before data collection began.
SETTING
All patients undergoing RFN between 12/06-1/10 at University Spine and Pain clinics.
METHODS
Subgroup analysis was performed based on response to MBB, a)100% pain relief and <100% pain relief after MBB 1 and 2 and a) those with > 8 hours and = 8 hours pain relief after MBB 1 and 2. Correlational analysis was conducted to determine the correlation between a) percent pain relief after MBB1 and 2 and percent change in pain after RFN and b) duration of pain relief after MBB 1 and 2 and percent change in pain relief after RFN.
OUTCOME MEASURES
Pain intensity, disability index, analgesic use, and patient perception of benefit.
RESULTS
Mean improvement of Disability scores at 3 months was 12.63 (P = 0.001), percent pain relief was 47.68% (P = 0.001). Patients with 100% pain relief after MBB 1 had greater improvement of disability scores (P = 0.008). Those with > 8 hours pain relief after MBB 1 had greater reduction in pain (P = 0.014). Pearson correlation analysis showed no correlation between percent pain relief or duration of pain relief after MBB and percent pain relief after RFN.
LIMITATIONS
This was a small observational study with short-term follow up.
CONCLUSION
Patients had improved disability scores and decreased pain after RFN. No correlation was seen between results on MBB and pain relief after RFN. It is still unclear how many medial branch blocks are needed and the criteria for MBB results before proceeding to RFN. | pubmed_56_11803 |
pubmed_40_25160 | Induced defenses mediate interactions between parasites sharing the same host plant, but the outcomes of these interactions are challenging to predict because of spatiotemporal variation in plant responses and differences in defense pathways elicited by herbivores or pathogens. Dissecting these mediating factors necessitates an approach that encompasses a diversity of parasitic feeding styles and tracks interactions over space and time. We tested indirect plant-mediated relationships across three tomato (Solanum lycopersicum) consumers: (1) the fungal pathogen-powdery mildew, Oidium neolycopersici; (2) a sap-feeding insect-silverleaf whitefly, Bemisia tabaci; and (3) a chewing insect-the leaf miner, Tuta absoluta. Further, we evaluated insect/pathogen responses on local vs. systemic leaves and over short (1 day) vs. long (4 days) time scales. Overall, we documented: (1) a bi-directional negative effect between O. neolycopersici and B. tabaci; (2) an asymmetrical negative effect of B. tabaci on T. absoluta; and (3) an asymmetrical positive effect of T. absoluta on O. neolycopersici. Spatiotemporal patterns varied depending on the species pair (e.g., whitefly effects on leaf miner performance were highly localized to the induced leaf, whereas effects on pathogen growth were both local and systemic). These results highlight the context-dependent effects of induced defenses on a diverse community of tomato parasites. Notably, the outcomes correspond to those predicted by phytohormonal theory based on feeding guild differences with key implications for the recent European invasion by T. absoluta. | 10.1007/s00442-013-2716-6 |
pubmed_904_24302 | The genus Paraholcostethus Belousova is reported from the Korean Peninsula for the first time with the description of a new species, Paraholcostethus irumiae sp. nov. The generic diagnosis of Paraholcostethus is slightly modified to accommodate the new species. Habitus, male and female internal and external genitalia are illustrated. A key to the species of the genus is also given. | 10.11646/zootaxa.4422.2.10 |
pubmed_180_22269 | BACKGROUND
Infant respiratory distress syndrome (IRDS) is the most common respiratory disease in preterm infants, and is associated with considerable morbidity and mortality. Valid data on IRDS are important in clinical epidemiological research.
OBJECTIVES
The objective of this study was to estimate the positive predictive value (PPV) of the IRDS diagnosis registered in the population-based Danish National Patient Registry according to the International Classification of Diseases, 8th and 10th revisions.
METHODS
Between January 1, 1977 and December 31, 2008, we randomly selected three patients per year, 96 in total, who were registered with an IRDS diagnosis in the Danish National Patient Registry and living in the northern part of Denmark. Data on the infants included information on the presence of predefined clinical symptoms. We defined IRDS as the presence of at least two of four clinical symptoms (tachypnea, retractions or nasal flaring, grunting, and central cyanosis), which had to be present for more than 30 minutes. Using medical record review as the reference standard, we computed the positive predictive value of the registered IRDS diagnosis including 95% confidence intervals (CIs).
RESULTS
We located the medical record for 90 of the 96 patients (94%), and found an overall PPV of the IRDS diagnosis of 81% (95% CI 72%-88%). This did not vary substantially between primary and secondary diagnoses. The PPV was higher, at 89% (95% CI 80%-95%), for preterm infants born before 37 weeks of gestation.
CONCLUSION
The PPV of the IRDS diagnosis in the Danish National Patient Registry is reasonable when compared with symptoms described in the corresponding medical records. The Danish National Patient Registry is a useful data source for studies of IRDS, particularly if restricted to preterm infants. Nonetheless, the potential impact of misclassification of the IRDS diagnosis must be considered. | 10.2147/CLEP.S44408 |
pubmed_699_3161 | Up to 90% of glyphosate was removed in 40 min by a 2:1 Mg2Al-layered double oxide (LDO) at pH 10, and the adsorption kinetics fitted a pseudo-second-order law. The adsorption isotherms were type L, and the Langmuir model best fitted the experimental data, with qmax of 158.22 μg/mg at 25 °C. The intraparticle diffusion model suggested that the adsorption process is dependent on the thickness and formation of the film at the solution/solid interface. The XRD results excluded the intercalation of glyphosate anions, and FTIR along with solid-state 13C and 31P MAS NMR confirmed that the glyphosate anions interact through the carboxylate and/or phosphonate moieties, both in end-on and side-on modes to the LDO surface. Glyphosate removal was also investigated in the presence of different anionic species, and simultaneous adsorption showed that carbonate and phosphate ions strongly influence glyphosate removal. | 10.1007/s11356-022-21703-y |
pubmed_996_13752 | The guttural pouch is a large, air-filled diverticulum of the auditory tube, present in the horse and other species. Lipid analysis of saline lavage from the equine guttural pouch has demonstrated the presence of phospholipids and neutral lipids in amounts that are variable but consistently greater than in any other species described. A stain specific for choline-containing phospholipids has demonstrated the presence of phospholipid-containing vesicles only within the cells of subepithelial, seromucoidlike glands, suggesting that these cells incorporate phospholipids in their secretions. The functional significance of surface-active agents in the guttural pouch may be different from that proposed for other species because of the unique anatomical design and the different proposed functions of the guttural pouch. | 10.1177/000348949410300508 |
pubmed_504_7644 | Essential amino acids (EAA) of inappropriate concentration have been reported to compromise the development of embryo. This study aimed to investigate the effect of EAA on the developmental competence of porcine embryos produced by either handmade cloning (HMC) or parthenogenetic activation (PA). In experiment 1, we examined the in vitro developmental competence of PA embryos after culture in PZM-3 containing different concentrations (v/v) of EAA (0%, 1%, and 2%). The results indicated that reducing the concentration of EAA from 2% to 1% significantly improved the blastocyst formation (36% vs. 54%), while 0% would compromise the blastocyst formation rate (54% vs. 38%). In experiment 2, we further investigated the effect of EAA concentration (1% and 2%) on the in vitro developmental competence and gene expression of HMC embryos. Blastocyst rate significantly increased by reducing concentration of EAA (41% vs. 53%) and those genes upregulated were enriched in oxidative phosphorylation, PPAR signaling pathway, and metabolism-related pathways. In experiment 3, the in vivo developmental competence of HMC embryos cultured in the medium supplemented with 1% EAA was examined. Embryos derived from both non-gene-modified fetal fibroblasts (FFs) and gene-modified fetal fibroblasts (GMFFs) were transferred to recipients. The pregnancy rates were 83% and 78% separately. Out of the pregnancies, 5 (FFs) and 6 (GMFFs) were successfully developed to term. Our study indicates that supplementing EAA to embryo culture medium at a concentration of 1% can improve the in vitro developmental competence of porcine HMC embryos and the blastocyst obtained can successfully develop to term, which could be beneficial for the production of gene-modified piglets. | 10.1089/cell.2020.0036 |
pubmed_88_9187 | A new in vitro method was developed for analyzing the capacity of sperm to bind to oviductal epithelium to determine whether this binding capacity could be used to predict nonreturn rates (NRR). Sperm binding was evaluated by counting 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide (JC-1)-labeled spermatozoa attached to oviductal epithelium and by measuring the surface area of the oviduct explants by means of an image analysis program. Hepes + Tyrode albumin lactate pyruvate (TALP) was a more useful medium than in vitro fertilization (IVF)-TALP, TCM-199 medium + 10% fetal calf serum, and TCM-199 medium alone for the investigation of sperm binding to oviductal explants. Oviduct explants with a surface area of < 20 000 micro m(2) provided more consistent results than did explants with a surface area of >100 000 micro m(2). A positive association was found between the log(e) transformed number of spermatozoa bound to 0.1 mm(2) oviductal epithelium and the NRR of the respective sires after 24 h of coincubation, provided that the membrane integrity of the sperm sample was >60%. Determination of the capacity of sperm to bind to oviductal explants could become a reliable in vitro method for predicting the NRR of a given sire. | 10.1095/biolreprod67.4.1073 |
pubmed_73_7950 | The aim of this study was to develop and test the practical utility of a perceived recovery status (PRS) scale. Sixteen volunteers (8 men, 8 women) performed 4 bouts of high-intensity intermittent sprint exercise. After completion of the baseline trial, in a repeated-measures design, subjects were given variable counterbalanced recovery periods of 24, 48, and 72 hours whereupon they repeated an identical intermittent exercise protocol. After a warm-up period, but before beginning each subsequent bout of intermittent sprinting, each individual provided their perceived level of recovery with a newly developed PRS scale. Similar to perceived exertion during exercise, PRS was based on subjective feelings. The utility of the PRS scale was assessed by measuring the level of agreement of an individual's perceived recovery relative to their performance during the exercise bout. Perceived recovery status and change (both positive and negative) in sprint performance during multiple bouts of repeated sprint exercise were moderately negative correlated (r = -0.63). Additionally, subjects were able to accurately assess level of recovery using the PRS scale indicated by correspondence with negative and positive changes in total sprint time relative to their previous session. The ability to detect changes in performance using a noninvasive psychobiological tool to identify differences in performance was independent of other psychological and physiological markers measured during testing, because there were no differences (p > 0.05) among ratings of perceived exertion (RPE), heart rate, blood lactate concentration, or session RPE values among any of the performance trials. Although further study is needed, current results indicate a subjective approach may be an effective means for assessing recovery from day to day, at least under similar conditions. | 10.1519/JSC.0b013e3181c69ec6 |
pubmed_762_15894 | Andropause is a problem that can be identified in some men as distinct from the changes associated with aging or chronic disease. These men have mild hypogonadism and a clinical picture that is well within the scope of urologists to identify and manage. Andropause is neither life threatening nor trivial and there are clinical guidelines published that will help to refine the understanding and definition of this condition. The character of andropause is distinct from profound hypogonadism in its relation to age, the scope and degree of contributing symptoms and the marginal reduction in testosterone. Testosterone is the established treatment for some men with andropause and the links between testosterone and cancer of the prostate create an overlap in management that places a premium on urological expertise. Obviously men with cancer of the prostate must not be given testosterone and some men may have clinical andropause and undetected cancer of the prostate. However, current understanding points to the fact that there is no additional risk from re-establishing a normal androgen environment (androgen replacement) in terms of initiating a new cancer of the prostate while testosterone will encourage growth of an established cancer. Therefore, the natural good practice of urology, and only urology, intrinsically encompasses the major issues inherent in the medical collision of cancer of the prostate and testosterone replacement. The good practice of urology includes the use of androgen replacement therapy in men who need it and have been assessed for the presence of cancer of the prostate. | pubmed_762_15894 |
pubmed_316_17746 | The inhibitory effect of potassium chloride and ammonium sulphate on purified human skin tryptase and bovine trypsin was studied enzyme-kinetically, using Z-Gly-Pro-Arg-pNA, Z-Gly-Pro-Arg-AMC, benzoyl-L-arginine ethyl ester (BAEE) and tosyl-L-arginine methyl ester (TAME) as substrates. With increasing salt concentrations, the curve of reaction velocity vs. substrate concentration changed from hyperbolic to sigmoidal when anilide substrates (Z-Gly-Pro-Arg-pNA or -AMC) were used. Only the Km value increased, while the Vmax value remained unchanged. The trend was similar with BAEE or TAME as the substrates. However, the effect of salt on the hydrolysis of these ester substrates was not as strong as on the hydrolysis of anilide substrates, and sigmoidal kinetics were not observed even at the highest KCl concentration (0.7 M) used. Heparin, used as a stabilizer, had no influence on this phenomenon, but it did slightly decrease the apparent Km and Vmax values in low-salt conditions. By comparison, trypsin was not as strongly affected by salt as tryptase, and the inhibition type was mixed competitive and non-competitive. The present results indicate that the salt acts on tryptase as an allosteric effector, and this should be carefully considered when enzyme kinetic parameters and enzyme activity of skin tryptase are measured. | 10.1016/0167-4838(88)90259-2 |
pubmed_439_25788 | We mapped the evidence on the type and strength of associations between a broad range of mental and physical conditions in children and adolescents, by carrying out an umbrella review, i.e., a quantitative synthesis of previous systematic reviews and meta-analyses. We also assessed to which extent the links between mental and physical conditions vary across disorders or, by contrast, are transdiagnostic. Based on a pre-established protocol, we retained 45 systematic reviews/meta-analyses, encompassing around 12.5 million of participants. In analyses limited to the most rigorous estimates, we found evidence for the following associations: ADHD-asthma, ADHD-obesity, and depression-asthma. A transdiagnostic association was confirmed between asthma and anxiety/ASD/depression/bipolar disorder, between obesity and ADHD/ASD/depression, and between dermatitis and ASD/ADHD. We conclude that obesity and allergic conditions are likely to be associated with mental disorders in children and adolescents. Our results can help clinicians explore potential links between mental and physical conditions in children/adolescent and provide a road map for future studies aimed at shading light on the underlying factors. | 10.1016/j.neubiorev.2022.104662 |
pubmed_999_22236 | INTRODUCTION
Left ventricular (LV) diastolic dysfunction (DD) is common after myocardial infarction (MI). Whereas current clinical assessment of DD relies on indirect markers including LV filling, finite element (FE) -based computational modeling directly measures regional diastolic stiffness. We hypothesized that an inverse deformation gradient (DG) method calculation of diastolic strain (IDGDS) allows the FE model-based calculation of regional diastolic stiffness (material parameters; MP) in post-MI patients with DD.
METHODS
Cardiac magnetic resonance (CMR) with tags (CSPAMM) and late gadolinium enhancement (LGE) was performed in 10 patients with post-MI DD and 10 healthy volunteers. The 3-dimensional (3D) LV DG from end-diastole (ED) to early diastolic filling (EDF; DGED→EDF) was calculated from CSPAMM. Diastolic strain was calculated from DGEDF→ED by inverting the DGED→EDF. FE models were created with MI and non-MI (remote; RM) regions determined by LGE. Guccione MPs C, and exponential fiber, bf, and transverse, bt , terms were optimized with IDGDS strain.
RESULTS
3D circumferential and longitudinal diastolic strain (Ecc;Ell) calculated using IDGDS in CSPAMM obtained in volunteers and MI patients were [Formula: see text] = 0.27 ± 0.01, [Formula: see text] = 0.24 ± 0.03 and [Formula: see text] = 0.21 ± 0.02, and [Formula: see text] = 0.15 ± 0.02, respectively. MPs in the volunteer group were CH = 0.013 [0.001, 0.235] kPa, [Formula: see text] = 20.280 ± 4.994, and [Formula: see text] = 7.460 ± 2.171 and CRM = 0.0105 [0.010, 0.011] kPa, [Formula: see text] = 50.786 ± 13.511 (p = 0.0846), and [Formula: see text] = 17.355 ± 2.743 (p = 0.0208) in the remote myocardium of post-MI patients.
CONCLUSION
Diastolic strain, calculated from CSPAMM with IDGDS, enables calculation of FE model-based regional diastolic material parameters. Transverse stiffness of the remote myocardium, , may be a valuable new metric for determination of DD in patients after MI. | 10.1016/j.jmbbm.2021.104431 |
pubmed_150_9478 | Oesophageal atresia (OA) with or without tracheoesophageal fistula (TOF) are rare anatomical congenital malformations whose cause is unknown in over 90% of patients. A genetic background is suggested, and among the reported genetic defects are copy number variations (CNVs). We hypothesized that CNVs contribute to OA/TOF development. Quantifying their prevalence could aid in genetic diagnosis and clinical care strategies. Therefore, we profiled 375 patients in a combined Dutch, American and German cohort via genomic microarray and compared the CNV profiles with their unaffected parents and published control cohorts. We identified 167 rare CNVs containing genes (frequency<0.0005 in our in-house cohort). Eight rare CNVs - in six patients - were de novo, including one CNV previously associated with oesophageal disease. (hg19 chr7:g.(143820444_143839360)_(159119486_159138663)del) 1.55% of isolated OA/TOF patients and 1.62% of patients with additional congenital anomalies had de novo CNVs. Furthermore, three (15q13.3, 16p13.3 and 22q11.2) susceptibility loci were identified based on their overlap with known OA/TOF-associated CNV syndromes and overlap with loci in published CNV association case-control studies in developmental delay. Our study suggests that CNVs contribute to OA/TOF development. In addition to the identified likely deleterious de novo CNVs, we detected 167 rare CNVs. Although not directly disease-causing, these CNVs might be of interest, as they can act as a modifier in a multiple hit model, or as the second hit in a recessive condition. | 10.1038/ejhg.2016.86 |
pubmed_428_7090 | Vascularization of tissue-engineered bone is a critical step in maintaining cell viability and advancing cell performance in vivo. In this study, a novel tri-culture system was developed to elicit pre-vascularization of calcium phosphate cement (CPC) scaffold in which human induced pluripotent stem cell-derived mesenchymal stem cells (hiPSMSCs) were seeded together with human umbilical vein endothelial cells (HUVECs) and pericytes. In a two-step methodology design, we first performed osteoinduction of the seeded hiPSMSCs on the CPC scaffold and then incorporated HUVECs and pericytes to the hiPSMSC-colonized CPC scaffold under a favorable culturing condition, with an objective to form a stable and functional capillary-like vascular network that sustained the engineered osseous tissue. The angiogenic and osteogenic effects of various culture strategies were studied and compared in nude rat model with cranial bone defects: (1) CPC scaffold alone (CPC control); (2) Pericyte-seeded CPC (CPC-pericytes); (3) HUVEC-seeded CPC (CPC-HUVECs); (4) hiPSMSC-seeded CPC (CPC-hiPSMSCs); (5) HUVECs co-cultured with hiPSMSCs on CPC (bi-culture group) and (6) HUVECs and pericytes co-cultured with hiPSMSCs on CPC (tri-culture group). After 12weeks, tri-culture group showed the highest amount of new bone (new bone area fraction of (45.3±2.7) %, p<0.05) and vessel formation (new blood vessel density of (50.7±3.8) vessels/mm2, p<0.05) in all groups. Our results demonstrated that the tri-culture strategy was effective in promoting angiogenesis and osteogenesis for bone tissue engineering. | 10.1016/j.msec.2017.05.035 |
pubmed_632_9765 | We report on the discovery of a new genus of microhylid subfamily Asterophryinae from northern and eastern Indochina, containing three new species. Vietnamophryne Gen. nov. are secretive miniaturized frogs (SVL<21 mm) with a mostly semi-fossorial lifestyle. To assess phylogenetic relationships, we studied 12S rRNA-16S rRNA mtDNA fragments with a final alignment of 2 591 bp for 53 microhylid species. External morphology characters and osteological characteristics analyzed using micro-CT scanning were used for describing the new genus. Results of phylogenetic analyses assigned the new genus into the mainly Australasian subfamily Asterophryinae as a sister taxon to the genus Siamophryne from southern Indochina. The three specimens collected from Gia Lai Province in central Vietnam, Cao Bang Province in northern Vietnam, and Chiang Rai Province in northern Thailand proved to be separate species, different both in morphology and genetics (genetic divergence 3.1%≤P≤5.1%). Our work provides further evidence for the "out of Indo-Eurasia" scenario for Asterophryinae, indicating that the initial cladogenesis and differentiation of this group of frogs occurred in the Indochina Peninsula. To date, each of the three new species of Vietnamophryne Gen. nov. is known only from a single specimen; thus, their distribution, life history, and conservation status require further study. | 10.24272/j.issn.2095-8137.2018.019 |
pubmed_455_3628 | We describe a simple and safe technique of cholédocho-jejunostomy using a Roux-en-Y jéjunal limb, to repair immediately biliary tract injuries, even when the conduits are thin. | 10.1016/s0003-3944(03)00056-7 |
pubmed_821_11399 | Despite still growing attraction mountain biking as a matter of sports traumatology still lacks relevant data based on large cross-sectional surveys. To obtain an overview of risk factors, types, and main body sites of injuries occurring in mountain biking we assessed the results of a questionnaire answered by 3873 athletes. A total of 8133 single lesions were reported by 3474 athletes, 36% of whom regularly participated in competitions. The incidence of injuries in mountain biking is comparable to that in other outdoor sports, the majority of injuries being minor. Mountain biking athletes were found to have an overall injury risk rate of 0.6% per year and 1 injury per 1000 h of biking. The main risk factors included slippery road surface, cyclist's poor judgement of the situation, and excessive speed, representing personal factors that could be altered by preventive measures. Of all injuries 14% were due to collision with some part of the bike, especially the pedals and the handlebar. While 75% of the injuries were minor, such as skin wounds and simple contusions, 10% were so severe that hospitalization was required. A breakdown of the injuries according to body site and frequency of occurrence is presented. | 10.1007/s001670000145 |
pubmed_804_17216 | BACKGROUND
This study aimed to investigate whether fatty infiltration (FI) measured on a single sagittal magnetic resonance imaging (MRI) slice can represent FI of the whole supraspinatus muscle.
METHODS
This study retrospectively reviewed the MRIs of 106 patients (age 50-79 years) divided into three rotator cuff tear-size groups: medium, large, and massive. Fat mass and muscle mass on all T1-weighted sagittal MRI scans (FA and MA) were measured. Of the total MRI scans, the Y-view was defined as the most lateral image of the junction of the scapular spine with the scapular body on the oblique sagittal T1-weighted image. Fat mass and muscle mass seen on this Y-view single slice were recorded as F1 and M1, respectively. Fat mass and muscle mass were also assessed on MRI scans lateral and medial to the Y-view. The means of fat mass and muscle mass on these three slices were recorded as F3 and M3, respectively. Average FI ratios (fat mass/muscle mass) of the three assessment methods (F1/M1, FA/MA, and F3/M3) were compared. Intraclass correlation coefficients (ICCs) were calculated for inter- and intraobserver reliability.
RESULTS
ICCs showed higher reliability (> 0.8) for all measurements. F1/M1 values were not statistically different from FA/MA and F3/M3 values (p > 0.05), except in males with medium and large tears. F3/M3 and FA/MA were not statistically different. The difference between F1/M1 and FA/MA did not exceed 2%.
CONCLUSIONS
A single sagittal MRI slice can represent the whole FI in chronic rotator cuff tears, except in some patient groups. We recommend measurement of FI using a single sagittal MRI slice, given the effort required for repeated measurements. | 10.4055/cios.2018.10.1.55 |
pubmed_467_8166 | BACKGROUND
There is conflicting data on the effect of carotid revascularization on cognitive function.
OBJECTIVE
To examine cerebral blood flow and cognitive function after carotid revascularization.
METHODS
Patients with unilateral, asymptomatic hemodynamically significant carotid artery stenosis (80% by computed tomography angiography or magnetic resonance angiography) were eligible. Cerebral blood flow was measured preoperatively and 1 month postoperatively using quantitative phase contrast magnetic resonance angiography. Preoperative flow impairment was defined as ipsilateral flow at least 20% less than contralateral flow (ie, an ipsilateral and/or contralateral flow ratio ≤0.8). Significant improvement in blood flow was defined as at least a 0.15 increase in flow ratio from pre- to postoperative. A control group was managed medically. Four cognitive domains were assessed at baseline, 1 month, and 6-12 months postoperatively.
RESULTS
Seventy-five patients were enrolled at 6 sites; 53 carotid endarterectomy, 11 carotid artery stenting, and 11 medical management only controls. Preoperative Trails B scores were similar between groups. Revascularization was associated with significant improvement in executive function (Trials B) while no improvement was observed in controls (P = .007). Of patients with improvement in middle cerebral artery (MCA) flow, 90% had improved Trails B scores compared to 46.5% of patients without MCA flow improvement (P = .01). Greater absolute improvement in mean Trails B scores was observed in patients with MCA flow improvement compared to those without (48 seconds versus 24.7 seconds, P = .001).
CONCLUSIONS
In a cohort of patient with asymptomatic carotid stenosis, improvement in MCA flow following carotid revascularization is associated with improvement in executive functioning. | 10.1016/j.jstrokecerebrovasdis.2020.104702 |
pubmed_581_14058 | Apoptosis and its molecular mediators, the caspases, have long been regarded as tumor suppressors and one hallmark of cancer is 'Evading Apoptosis'. However, recent work has suggested that apoptotic caspases can also promote proliferation and tumor growth under certain conditions. How caspases promote proliferation and how cells are protected from the potentially harmful action of apoptotic caspases is largely unknown. Here, we show that although caspases are activated in a well-studied neoplastic tumor model in Drosophila, oncogenic mutations of the proto-oncogene Ras (Ras) maintain tumorous cells in an 'undead'-like condition and transform caspases from tumor suppressors into tumor promotors. Instead of killing cells, caspases now promote the generation of intra- and extracellular reactive oxygen species (ROS). One function of the ROS is the recruitment and activation of macrophage-like immune cells which in turn signal back to tumorous epithelial cells to activate oncogenic JNK signaling. JNK further promotes and amplifies caspase activity, thereby constituting a feedback amplification loop. Interfering with the amplification loop strongly reduces the neoplastic behavior of these cells and significantly improves organismal survival. In conclusion, Ras-modified caspases initiate a feedback amplification loop involving tumorous epithelial cells and macrophage-like immune cells that is necessary for uncontrolled tumor growth and invasive behavior. | pubmed_581_14058 |
pubmed_326_1718 | An immunohistochemical stain to the c-ErbB-2 protein was performed in 225 paraffin-embedded tissue blocks from patients with locally advanced gastric cancer who underwent curative resection. The overexpression of the c-ErbB-2 protein was observed in 27.4% of the patients. The c-ErbB-2 positivity showed a statistically significant correlation with nodal status and stage. The patients with an overexpression of the c-ErbB-2 protein had a tendency to a shorter survival than those without, but it was not statistically significant (p = 0.08). The 5-year survival rate after surgery was 54% in the negative staining group to the c-ErbB-2 protein and 49% in the positive staining group. This suggests that the c-ErbB-2 protein has a possible role in lymph node metastasis. Therefore overexpression of the c-ErbB-2 protein is a useful indicator of disease progression in gastric carcinoma patients who received curative surgery. | 10.1159/000227559 |
pubmed_671_5568 | After observing a case of pemphigoid in a 5-month-old infant, verified inmunologically, we comment on the clinical, histological, biochemical and immunological tests and review the benign chronic bullous dermatosis of the childhood. | pubmed_671_5568 |
pubmed_169_7765 | The effect of chronic ethanol administration with and without sucrose on the lipogenic enzymes of liver and adipose tissue of rats was studied. Ethanol markedly influenced the adipose lipogenic enzymes at 28 days. Sucrose caused a 2-10fold increase in lipogenic enzymes of both adipose and liver. | 10.1007/BF01936960 |
pubmed_61_20707 | Dicarboxylic acids (DA) are formed from the omega-oxidation of monocarboxylic acids when the beta-oxidation of free fatty acids is impaired. Medium-chain DA have the peculiar characteristic of being water soluble due to the presence of two carboxylic terminal groups in the molecule. Contrary to both long- and medium-chain triglycerides which are administered as emulsions, they can be given by a peripheral vein as inorganic salts. DA are beta-oxidized at level of both peroxisomes and mitochondria via carnitine-independent pathway. The products of beta-oxidation of odd-chain DA are acetyl-CoA and malonyl-CoA, which cannot be oxidized further, are used in lipogenesis. Moreover even-chain DA produce acetyl-CoA and succinyl-CoA, which is a gluconeogenetic precursor. Azelaic acid (C9), does not show acute or chronic toxicity effects in animals but much of it is lost in urine (more than 50% of the given dose). Sebacic acid (C10) is lost in urine to a smaller extent (about 12% of the administered dose) and its energy density (6.64 kcal/g) is greater than that of C9 (4.97 kcal/g). Dodecanedioic acid (C12) seems to be the best candidate for parenteral nutrition, because it is eliminated in the urine only in minimal amounts (3.90% of the given dose), it is rapidly utilized by tissues, and it has a high energy density (7.20 kcal/g). | 10.1016/s0261-5614(95)80011-5 |
pubmed_433_7145 | This review evaluates current knowledge about obsessive-compulsive disorder (OCD), with the goal of providing a roadmap for future directions in research on the psychopharmacology of the disorder. It first addresses issues in the description and diagnosis of OCD, including the structure, measurement, and appropriate description of the disorder and issues of differential diagnosis. Current pharmacotherapies for OCD are then reviewed, including monotherapy with serotonin reuptake inhibitors and augmentation with antipsychotic medication and with psychologic treatment. Neuromodulatory therapies for OCD are also described, including psychosurgery, deep brain stimulation, and noninvasive brain stimulation. Psychotherapies for OCD are then reviewed, focusing on behavior therapy, including exposure and response prevention and cognitive therapy, and the efficacy of these interventions is discussed, touching on issues such as the timing of sessions, the adjunctive role of pharmacotherapy, and the underlying mechanisms. Next, current research on the neurobiology of OCD is examined, including work probing the role of various neurotransmitters and other endogenous processes and etiology as clues to the neurobiological fault that may underlie OCD. A new perspective on preclinical research is advanced, using the Research Domain Criteria to propose an adaptationist viewpoint that regards OCD as the dysfunction of a normal motivational system. A systems-design approach introduces the security motivation system (SMS) theory of OCD as a framework for research. Finally, a new perspective on psychopharmacological research for OCD is advanced, exploring three approaches: boosting infrastructure facilities of the brain, facilitating psychotherapeutic relearning, and targeting specific pathways of the SMS network to fix deficient SMS shut-down processes. SIGNIFICANCE STATEMENT: A significant proportion of patients with obsessive-compulsive disorder (OCD) do not achieve remission with current treatments, indicating the need for innovations in psychopharmacology for the disorder. OCD may be conceptualized as the dysfunction of a normal, special motivation system that evolved to manage the prospect of potential danger. This perspective, together with a wide-ranging review of the literature, suggests novel directions for psychopharmacological research, including boosting support systems of the brain, facilitating relearning that occurs in psychotherapy, and targeting specific pathways in the brain that provide deficient stopping processes in OCD. | 10.1124/pr.119.017772 |
pubmed_533_8350 | New evidence suggests that closure of a patent foramen ovale (PFO) plus medical therapy (MT; antiplatelet or anticoagulation) is superior to MT alone to prevent recurrent cryptogenic stroke. We performed a meta-analysis of randomized controlled trials that compared PFO closure plus MT with MT alone in patients with cryptogenic stroke. The efficacy end points were recurrent stroke, transient ischemia attack, and death. The safety end points were major bleeding and newly detected atrial fibrillation. Trials were pooled using random effects and fixed effects models. A trial sequential analysis was performed to assess if the current evidence is sufficient. Risk ratios (RR) were calculated for pooled estimates of risk. Five randomized controlled trials (3,440 patients) were included. Mean follow-up was 4.1 years. PFO closure reduced the risk of recurrent stroke by 58% (RR 0.42, 95% CI 0.20 to 0.91, p = 0.03). The number needed to treat was 38. The cumulative Z-line crossed the trial sequential boundary, suggesting there is adequate evidence to conclude that PFO closure reduces the risk of recurrent stroke by 60%. PFO closure did not reduce the risk of transient ischemia attack (RR 0.78, 95% CI 0.53 to 1.15, p = 0.21), mortality (RR 0.74, 95% CI 0.35 to 1.60, p = 0.45), or major bleeding (RR 0.96, 95% CI 0.42 to 2.20, p = 0.93); it did increase the risk of atrial fibrillation (RR 4.69, 95% CI 2.17 to 10.12, p <0.0001). | 10.1016/j.amjcard.2017.11.037 |
pubmed_888_20410 | BACKGROUND
We identified the gene mutations in two Chinese pedigree of type I hereditary protein C deficiency and type I hereditary antithrombin deficiency.
METHODS
The plasma level of protein C activity (PC:A), protein C antigen (PC:Ag), protein S activity, antithrombin activity (AT:A) and antithrombin antigen (AT:Ag) of propositi and two family members were detected using ELISA and chromogenic assay, respectively. All exons and intron-exon boundaries of protein C gene and antithrombin gene were analyzed by direct sequencing of the corresponding amplified PCR products in DNA from the propositus.
RESULTS
The plasma PC:A and PC:Ag of propositus 1 was 26% and 1.43 mg/dl, respectively. The PC:Ag and PC:A of his father were normal. The decreased PC:A level was seen in his mother and 4 of his maternal pedigree. PS:A and AT:A were all normal in pedigree 1 members. A C5498T heterozygous mutation in exon 3 of protein C gene, resulting in the substitution of Arg for Trp at the 15th amino acid, was identified in propositus 1 and 8 of his relatives. The plasma AT:A and AT:Ag of propositus 2 was 48.6% and 10.4 mg/dl, respectively. The reduced AT:A and AT:Ag levels were found in his father and 5 of paternal pedigree. PC:A, PC:Ag and PS:A were all in normal range. A heterozygous 13387-9G deletion in exon 6 of antithrombin gene was identified in propositus 2. This mutation introduced a frameshift and a premature stop at codon 426 and existed in 6 members of pedigree 2.
CONCLUSION
The C5498T heterozygous mutation in exon 3 of protein C gene, first reported in China, leads to type I hereditary protein C deficiency. The 13387-9G deletion, a novel mutation, can cause antithrombin deficiency and thrombosis. | pubmed_888_20410 |
pubmed_447_10693 | The state of the art in practical external quality assessment (EQA) in the Federal Republic of Germany is described. Two organizations, INSTAND (Institute for Standardization and Documentation in Medical Laboratories) and the German Society for Clinical Chemistry (DGKCh) have been appointed by the central government to organize and run EQA schemes. Although legislation rules that participation for seven analytes (five steroids, thyroxine and theophyllin) is mandatory, using gas chromatography-isotope dilution-mass spectrometry as the reference method, this has been suspended. For remuneration from the local health insurance organizations, the laboratory must provide evidence of having participated in one of the two national EQA schemes. The schemes are run between 3 and 6 times yearly and cover the whole field of endocrinology and related substances. | pubmed_447_10693 |
pubmed_1057_10666 | Up to 35% of small bowel neuroendocrine tumors (SBNETs) may present with an acute intra-abdominal complication including obstruction, perforation, bleeding or ischemia and may require emergency surgical treatment in centers not normally accustomed to managing patients with neuroendocrine tumors. These patients may have a known diagnosis of SBNET, be suspected as suffering from SBNET or have SBNET diagnosed as an incidental finding on presenting radiology or postoperative pathology. Perioperative priorities include obtaining both clinical and radiological staging with cross-sectional imaging and clinical examination, screening for the presence of carcinoid syndrome and right-sided cardiac disease and assessment of prognosis. Intraoperatively careful attention should be paid to noting the presence and location of multifocal primary and metastatic disease. Ideally, surgical resection with mesenteric lymph node dissection is the treatment of choice for obstructing and perforating lesions. Extended lymphadenectomy along the SMA, SMV and behind the pancreas should be primarily considered an elective procedure. In unwell patients with advanced disease surgical bypass (jejuno or ileocolic) or proximal defunctioning should be undertaken but, given the excellent long-term survivals in patients with stage IV disease, could be considered bridging procedures to elective resection following formal staging and multidisciplinary review. | 10.1007/s00268-020-05689-7 |
pubmed_784_4734 | A rare case is presented of a nonruptured aneurysm of the intraorbital ophthalmic artery in which successful resection of the aneurysm resulted in improvement of preoperative progressive signs caused by the mass effect of the aneurysm. The surgical management of this rare entity is discussed with special attention given to the collateral circulation of the ophthalmic artery from the external carotid artery. | 10.1227/00006123-199212000-00017 |
pubmed_1118_13669 | The COVID-19 pandemic has contributed to poor health due to a decrease in healthcare utilization and those with mental health problems may be impacted. For this analysis, data came from a cross-sectional, nationally representative December 2020 survey. Logistic regression analyses examined associations between (1) mental distress and delayed medical visits, (2) mental distress and missed prescription refills, controlling for sociodemographics, pre-existing chronic conditions, and access to health insurance. We found that, compared to those that exhibited normal levels of mental distress, those with mild (aOR = 2.83, 95% CI = 2.47-3.24), moderate (aOR = 3.43, 95% CI = 2.95-3.99), and severe (aOR = 4.96, 95% CI = 4.21-5.84) mental distress showed greater odds of delaying medical visits. Similarly, compared to those that exhibited normal levels of mental distress, those with mild (aOR =3.93, 95% CI = 3.04-5.09), moderate (aOR =6.52, 95% CI = 5.07-8.43), and severe (aOR =8.69, 95% CI = 6.71-11.32) mental distress showed greater odds of missing prescription refills. Our study shows that individuals who showed signs of mental distress had increased odds of delayed medical visits and missed prescription refills, compared to those that showed normal levels of mental distress. | 10.1016/j.ypmed.2022.107195 |
pubmed_809_327 | Sex steroid signalling determines female and male sexual development and maintains the female and male phenotype in adults. Steroids carry out their function by activation of their cognate intracellular receptor, which is a ligand-dependent transcription factor. Steroid receptors function by binding to specific structural elements in the regulatory regions of target genes and by recruitment of cofactors by protein-protein interaction. Cofactors might display enzymatic activities that modify histones and other proteins. Cofactors also include proteins that modulate the chromatin structure and protein complexes that function as bridging factors between the multi-protein complexes. This review focuses mainly on the function of the androgen receptor and its cofactors and their role in androgen insensitivity syndrome. | 10.1016/j.beem.2007.07.002 |
pubmed_1037_13307 | SUMMARY
We present several recent improvements to minimap2, a versatile pairwise aligner for nucleotide sequences. Now minimap2 v2.22 can more accurately map long reads to highly repetitive regions and align through insertions or deletions up to 100kb by default, addressing major weakness in minimap2 v2.18 or earlier.
AVAILABILITY AND IMPLEMENTATION
https://github.com/lh3/minimap2. | 10.1093/bioinformatics/btab705 |
pubmed_598_15062 | BACKGROUND
Recently, an emerging group of studies has reported the association between Body Mass Index (BMI) and suicidal ideation in the Western countries. However, this relationship is still unclear with controversial results, and we have little knowledge about this relationship in China which is one of few countries reported higher suicide rates.
METHODS
This study aims to analyze the association between BMI and suicidal ideation among seniors (≥60 years old) in Shandong, China. A total of 3313 seniors were included in the data analysis. Suicidal ideation, weight, height, socio-demographic and psychological variables were evaluated in this study. Logistic regression was conducted to explore the association between BMI and suicidal ideation among male and female seniors.
RESULTS
The results showed that 4.2% of the seniors reported suicidal ideation, and 3.4% for men, 4.9% for women. After controlling social-demographic variables, economic status, physical disease, social support and mental health, an inverse relationship between BMI and suicidal ideation was found for men, but not for women. Mental health was still an important factor associated with suicidal ideation.
CONCLUSION
The results inform health care professors that underweight in male seniors can be associated with higher risk of suicidal ideation in China. | 10.1016/j.comppsych.2018.01.008 |
pubmed_299_14579 | BACKGROUND AND OBJECTIVES
The primary objective of this study was to compare the analgesic efficacy of combined suprascapular and axillary nerve block (SSAX) with interscalene block (ISB) after arthroscopic shoulder surgery. Our hypothesis was that ultrasound-guided SSAX would provide postoperative analgesia equivalent to ISB.
METHODS
Sixty adult patients undergoing arthroscopic shoulder surgery received either SSAX or ISB prior to general anesthesia, in a randomized fashion. Pain scores, satisfaction, and adverse effects were recorded in the recovery room, 6 hours, 24 hours, and 7 days after surgery.
RESULTS
Combined suprascapular and axillary nerve block provided nonequivalent analgesia when compared with ISB at different time points postoperatively, except on postoperative day 7. Interscalene block had better mean static pain score in the recovery room (ISB 1.80 [95% confidence interval [CI], 1.10-2.50] vs SSAX 5.45 [95% CI, 4.40-6.49; P < 0.001]). At 24 hours, SSAX had better mean static pain score (ISB 6.35 [95% CI, 5.16-7.54] vs SSAX 3.92 [95% CI, 2.52-5.31]; P = 0.01) with similar satisfaction between the groups.
CONCLUSIONS
Combined suprascapular and axillary nerve block provides nonequivalent analgesia compared with ISB after arthroscopic shoulder surgery. While SSAX provides better quality pain relief at rest and fewer adverse effects at 24 hours, ISB provides better analgesia in the immediate postoperative period. For arthroscopic shoulder surgery, SSAX can be a clinically acceptable analgesic option with different analgesic profile compared with ISB. | 10.1097/AAP.0000000000000436 |
pubmed_1129_14090 | Background
Evidence shows that lipid ratios perform better than individual lipids in predicting cardiovascular risk. The lipid ratio serves as a quick and simple tool for identifying subclinical atherosclerosis. The population at risk especially perimenopausal and menopausal women should be monitoring to prevent cardiovascular disease in the future.
Objective
To examine the association between lipid ratios and subclinical atherosclerosis by carotid intima media thickness (CIMT) in perimenopausal/menopausal women.
Material and Method
A cross-sectional study was conducted with 130 participants aged 40 to 80 years between February 2015 and January 2016 in Suranaree University of Technology Hospital, Thailand. CIMTs were assessed using a highresolution B mode ultrasound system. Traditional anthropometry, body mass index (BMI), waist circumference (WC), and parameters including blood pressure, fasting plasma glucose, lipid profile [Total cholesterol (TC), Triglyceride (TG), Highdensity lipoprotein cholesterol (HDL-C) and Low-density lipoprotein cholesterol (LDL-C)], and CIMT were assessed in all subjects. All lipid ratios were calculated.
Results
One hundred thirty perimenopausal/menopausal participants were included in this study. Of those participants, 41% were central obese phenotype and 22% had abnormal CIMT that can identify atherosclerosis. Age and systolic blood pressure in atherosclerosis group were higher than normal CIMT group; <0.01 and <0.01, respectively. Lipid ratio in normal CIMT was higher than atherosclerotic group but not statistically significance except TG/HDL-C (p = 0.03). All lipid ratios and single lipid parameters lacked prediction for the presence of early atherosclerosis.
Conclusion
All of lipid ratios, TC/HDL-C, TG/HDL-C, and LDL-C/HDL-C were not identified as early subclinical atherosclerosis among perimenopausal/menopausal women. | pubmed_1129_14090 |
pubmed_198_13465 | Herein we describe a 59-year-old man with left renal artery emboli treated with selective intra-arterial infusion followed by systemic intravenous infusion of urokinase. Total dose of infused urokinase was 2,712,000 units. Although the function of the affected kidney was not recovered, we have demonstrated successful clot lysis and no complication. Selective or systemic thrombolytic therapy is extremely promising as a method of treatment of renal artery embolism, especially in the poor operative candidate. The availability of this potentially efficacious therapy suggests that aggressive diagnostic studies be performed early in patients suspected of having renal artery embolism. | pubmed_198_13465 |
pubmed_488_1820 | Products, substrates, and inhibitors of the threonine dehydratase from sheep liver (EC 4.2.1.16) have been investigated by proton nuclear magnetic resonance and optical rotation. The alpha-ketobutyrates produced from L-threonine and L-allothreonine in 2H2O have been shown to incorporate a single deuterium into the beta position. The dehydratase forms R-alpha-ketobutyrate-beta-d from L-threonine and L-allothreonine. The alpha protons of the substrates, threonine and allothreonine, do not exchange in the presence of the dehydratase. In the presence of dehydratase, the competitive inhibitors L-cysteine and L-alanine undergo alpha-proton exchange. Highly purified dehydratase has been used to determine kinetic parameters for the usbstrates L-threonine, L-allothreonine, L-serine, and L-chloroalanine. L-Chloroalanine, in addition to being a substrate, inhibits the dehydratase in a manner kinetically identical with that of L-serine. | 10.1021/bi00662a016 |
pubmed_886_22937 | The repeating unit of cepacian, the exopolysaccharide produced by the majority of the microorganisms belonging to the Burkholderia cepacia complex, was isolated from inner bacterial membranes and investigated by mass spectrometry, with and without prior derivatisation. Interpretation of the mass spectra led to the determination of the biological repeating unit primary structure, thus disclosing the nature of the oligosaccharide produced in vivo. Moreover, mass spectra recorded on the native sample revealed that acetyl substitution was very variable, producing a mixture of repeating units containing zero to four acyl groups. At the same time, finding acetylated oligosaccharides showed that binding of these substituents occurred in the cellular periplasmic space, before the polymerisation process took place. In the chromatographic peak containing the repeating unit, oligosaccharides shorter than the repeating unit co-eluted. Mass spectrometric analysis showed that they were biosynthetic intermediates of the repeating unit and further investigation revealed the biosynthetic sequence of cepacian building block. | 10.1016/j.carres.2010.03.029 |
pubmed_883_2952 | Removal of the petiole from detached betel leaves delays onset of leaf senescence; the delay is nearly proportional to the extent of depetiolation. An agar diffusate from intact midrib or excised petioles induces normal senescence in depetiOlated leave. | 10.1126/science.167.3917.387 |
pubmed_993_6749 | Forty-seven cases of cerebellar abscess have been reviewed, 93% of which were secondary to otogenic disease. There has been little change in the annual incidence during the period of time under review. The overall mortality was 41%, but with successive decades the mortality has increased. Three factors appear to be of importance in determining survival: the patient's ability to control his infection; reduction of the effect of the posterior fossa mass, preferably by complete excision of the abscess under antibiotic cover; and, in the case of otogenic abscess, an adequate radical mastoidectomy with bone removal to the site of attachment of the abscess to the dura mater. | 10.1136/jnnp.38.5.429 |
pubmed_872_7404 | At Dalhousie University, interprofessional (IP) learning modules are used to help future health care professionals learn to work together in resolving complex problems. One module, "From Family Violence to Health," features the role of dental professionals. This paper describes the evolution of this module from the year 2000. By February 2003, 1,182 students from 15 health care professions had completed the module. Qualitative evaluation in years 1 and 2 of the program (2000 and 2001) revealed that, before participating in the IP module, many students were able to identify a role for themselves in the recognition of family violence and knew their responsibility to report incidents. However, after participating in the module, they had a greater understanding of the reporting of family violence, a more comprehensive and supportive perspective, increased recognition of how health care professionals could work together and improved awareness of the roles of other professions. In a quantitative evaluation in year 3 (2002), mean student ratings on a scale of 1 to 5 indicated that the IP module was relevant (4.2), increased their understanding of family violence (4.0), and had some impact in promoting IP learning (3.8). As health care delivery becomes more focused on care teams and system thinking, the provision of IP training is expected to increase. The Dalhousie University IP modules (available at http://www.dal.ca/~fhp/ipl/index.html) address health and social problems for which it is critical that health care and other professionals work together. Feedback from practitioners on the development of IP education is welcomed, particularly with regard to the IP module addressing family violence. | pubmed_872_7404 |
pubmed_601_7174 | cDNA clones to human prepro-gastrin-releasing peptide (prepro-GRP) mRNA detect synthesis of prepro-GRP-related transcripts in 4 of 7 small cell lung cancer (SCLC) cell lines and 1 of 2 metastatic SCLC tumors examined. A correlation is noted between prepro-GRP gene expression and the occurrence of bombesin-related immunoreactivity in SCLC cell lines. Examination of the structure of prepro-GRP transcripts found in SCLC reveals three types of prepro-GRP mRNA which differ in the structure of a putative GRP-associated peptide in the pro-GRP precursor. The subcellular distribution of prepro-GRP-related RNAs and structure of SCLC-derived prepro-GRP cDNA clones suggest that all three types of transcript could function as mRNAs, although there are differences in the prevalence of the different RNA types in different cellular compartments. Comparison of the sequence of cDNA clones with the sequence of a genomic prepro-GRP clone reveals that the three forms of prepro-GRP mRNA arise from a single primary transcript which undergoes alternative processing from two splice donor sites to two splice acceptor sites. The predicted amino acid sequence of the translated products of the three mRNAs are quite distinct, leading to predicted pro-GRP molecules of differing structure. | pubmed_601_7174 |
pubmed_385_9477 | One of the most critical and contentious issues for specialist and nonspecialist professionals in the coming decades will be to evaluate the outcomes of health care services. Performance measures are imperative for elective orthodontics, because of the relatively weak evidence that they lead to significant improvements in dental and oral health, occlusal function, and psychological well-being of patients. Such measures are particularly crucial for orthodontic treatment eligible for benefit payments, because they will assure third-party dental insurers that the annual premiums levied from governments (taxes), employers (in lieu of salary increments), and individuals (in lieu of other discretionary expenditures) are well spent (ie, not wasted). Performance measures will also improve the "standards of orthodontic practice," so the continued integrity of the profession is contingent on their development. | 10.1016/S0889540604005281 |
pubmed_644_23246 | It is well established that reproductive function is metabolically gated. However, the mechanisms whereby energy stores and metabolic cues influence appetite, energy homeostasis and fertility are yet to be completely understood. Adipose tissue is no longer considered as only a depot to store excess energy. Recent findings have identified numerous genes, several neurotrophic factors, interleukins, insulin-like growth factor binding protein-5, ciliary neurotrophic factor and neuropeptide Y (NPY) as being expressed by adipose tissue during pubertal development. These studies demonstrated for the first time the expression of several major adipokines or cytokines in pig adipose tissue which may influence local and central metabolism and growth. Leptin appears to be the primary metabolic signal and is part of the adipose tissue-hypothalamic regulatory loop in the control of appetite, energy homeostasis and luteinizing hormone (LH) secretion. Leptin's actions on appetite regulation are mediated by inhibition of hypothalamic NPY and stimulation of proopiomelanocortin. Its effects on gonadotropin-releasing hormone (GnRH)/LH secretion are mediated by NPY and kisspeptin. Thus, leptin appears to be an important link between metabolic status, the neuroendocrine axis and subsequent fertility in the gilt and sow. | 10.1111/j.1439-0531.2008.01173.x |
pubmed_567_20829 | A full-length cDNA clone of a serine proteinase, mouse brain serine proteinase (mBSP), was isolated from a mouse brain cDNA library. mBSP, which has been recently reported to be expressed in the hair follicles of nude mice, is most similar (88% identical) in sequence to rat myelencephalon-specific protease. The mBSP mRNA was steadily expressed in the brain of adult mice with a transient expression in the early fetal stage during development. The genomic structure of the mouse gene for mBSP was determined. The gene, which is mapped to chromosome 7B4-B5, is about 7.4 kilobases in size and contains 7 exons. Interestingly, the 5'-untranslated region of the mBSP gene was interrupted by two introns. In situ hybridization analyses revealed that mBSP is expressed in the white matter of the cerebellum, medulla oblongata, and capsula interna and capsula interna pars retrolenticularis of mouse brain. Further, mBSP was immunolocalized to the neuroglial cells in the white matter of the cerebellum. Recombinant mBSP was produced in the bacterial expression system and activated by lysyl endopeptidase digestion, and the activated enzyme was purified for characterization. The enzyme showed amidolytic activities preferentially cleaving Arg-X bonds when 4-methylcoumaryl-7-amide-containing peptide substrates were used. Typical serine proteinase inhibitors, such as diisopropyl fluorophosphates, phenylmethanesulfonyl fluoride, soybean trypsin inhibitor, aprotinin, leupeptin, antipain, and benzamidine, strongly inhibited the enzyme activity. The recombinant mBSP effectively hydrolyzed fibronectin and gelatin, but not laminin, collagens I and IV, or elastin. These results suggest that mBSP plays an important role in association with the function of the adult mouse brain. | 10.1074/jbc.275.15.11050 |
pubmed_488_9922 | Of 222 patients with pneumonia in St Vincent's Hospital, Sydney, in 1972, more were affected by bronchopneumonia (53%) than lobar pneumonia (46%). Two-thirds of the patients were males and 86% were aged 40 years or more. Only 59% had any bacteriological studies performed. It was unusual to isolate pathogens from persons who had received antibiotics before cultures were taken, but of cultures taken from persons not receiving antibiotics, 65% yielded pneumococci. Infections due to Staphylococcus aureus, pseudomonas and enterobacteria were uncommon. Haemophilus influenzae appeared to be a co-pathogen in bronchopneumonia more than in lobar pneumonia. The mortality in lobar pneumonia was acceptably low (4%), but was generally high in bronchopneumonia, being 32% when the condition occurred after surgical operations and 35% when this form of pneumonia complicated other normally non-terminal medical diseases. The mortality was 17% in primary bronchopneumonia. | 10.5694/j.1326-5377.1976.tb115356.x |
pubmed_669_17668 | BACKGROUND
Axial Spondyloarthritis (axSpA) is a chronic, inflammatory rheumatic disease that affects the axial skeleton, causing pain, stiffness, and fatigue. Genetics and environmental factors such as microbiota and microtrauma are known causes of disease susceptibility and progression. Murine models of axSpA found a decisive role for biomechanical stress as an inducer of enthesitis and new bone formation. Here, we hypothesize that muscle properties in axSpA patients are compromised and influenced by genetic background.
OBJECTIVES
To improve our current knowledge of axSpA physiopathology, we aim to characterize axial and peripheral muscle properties and identify genetic and protein biomarker that might explain such properties.
METHODS
A cross-sectional study will be conducted on 48 participants aged 18-50 years old, involving patients with axSpA (according to ASAS classification criteria, symptoms duration < 10 years) and healthy controls matched by gender, age, and levels of physical activity. We will collect epidemiological and clinical data and perform a detailed, whole body and segmental, myofascial characterization (focusing on multifidus, brachioradialis and the gastrocnemius lateralis) concerning: a) Physical Properties (stiffness, tone and elasticity), assessed by MyotonPRO®; b) Strength, by a dynamometer; c) Mass, by bioimpedance; d) Performance through gait speed and 60-second sit-to-stand test; e) Histological and cellular/ molecular characterization through ultrasound-guided biopsies of multifidus muscle; f) Magnetic Resonance Imaging (MRI) characterization of paravertebral muscles. Furthermore, we will perform an integrated transcriptomics and proteomics analysis of peripheral blood samples.
DISCUSSION
The innovative and multidisciplinary approaches of this project rely on the elucidation of myofascial physical properties in axSpA and also on the establishment of a biological signature that relates to specific muscle properties. This hitherto unstudied link between gene/protein signatures and muscle properties may enhance our understanding of axSpA physiopathology and reveal new and useful diagnostic and therapeutic targets. | pubmed_669_17668 |
pubmed_828_18437 | High thymidine phosphorylase (TP) expression is significantly correlated with poor prognosis in patients with nasopharyngeal carcinoma (NPC). NPC is an Epstein-Barr Virus (EBV)-associated cancer in which the EBV-encoded oncogene product, latent membrane protein 1 (LMP1), is expressed in approximately 60% of tumor tissues. However, no previous study has examined whether LMP1 is involved in up-regulating TP expression in NPC tissues. We herein show that LMP1 expression is correlated with TP expression in tumor cells, as examined by quantitative RT-PCR and immunohistochemical staining. We further show that the CTAR1 and CTAR2 domains of LMP1 mediate TP induction, as demonstrated by quantitative RT-PCR and Western blot analyses using LMP1 deletion and site-specific mutants. Mechanistically, LMP1-mediated TP induction is abolished by inhibitors of NF-kappaB and p38 MAPK, dominant-negative IkappaB and p38, and siRNA-mediated knockdown of p38 MAPK. Clinically, there were significant correlations among the expression levels of TP, activated p65, and phospho-p38 MAPK in NPC biopsy samples. Functionally, LMP1-mediated induction of TP expression enhanced the sensitivity of NPC cells to the chemotherapeutic prodrug, 5'-DFUR. Our results provide new insights into the roles of LMP1-mediated NF-kappaB and p38 MAPK signaling pathways in TP induction, potentially suggesting new therapeutic strategies for the treatment of NPC. | 10.1016/j.cellsig.2010.03.008 |
pubmed_1092_18230 | BACKGROUND
Quality measures are now commonplace and are increasingly tied to financial incentives. We reviewed the existing quality measures that address the upper limb and tested the null hypothesis that structure (capacity to deliver care), process (appropriate care), and outcome (the result of care) measures are equally represented.
METHODS
We systematically reviewed MEDLINE/PubMed, Embase, Google Scholar, the American Academy of Orthopaedic Surgeons Clinical Practice Guidelines, the National Quality Forum, the Agency for Healthcare Research and Quality, and the Physician Quality Reporting System for quality measures addressing upper limb surgery. Measures were characterized as structure, process, or outcome measures and were categorized according to their developer and their National Strategy for Quality Improvement in Health Care (National Quality Strategy) priority as articulated by the U.S. Department of Health & Human Services.
RESULTS
We identified 134 quality measures addressing the upper limb: 131 (98%) process and three (2%) outcome measures. The majority of the process measures address the National Quality Strategy priority of effective clinical care (90%), with the remainder addressing communication and care coordination (5%), person and caregiver-centered experience and outcomes (4%), and community/population health (1%).
CONCLUSIONS
Our review identified opportunities to develop more measures in the structure and outcome domains as well as measures addressing patient and family engagement, public health, safety, care coordination, and efficient use of resources. The most common existing measures-process measures addressing care-might not be the best measures of upper limb surgery quality given the relative lack of evidence for their use in care improvement. | 10.2106/JBJS.15.00651 |
pubmed_880_7476 | PURPOSE
The theoretical superiority of mobile-bearing total knee arthroplasties (TKAs) has not yet been proven in clinical studies. The aim of the current study was to compare and to analyse in a patient population that had received either a fixed or a mobile TKA differences in gait analysis electromyography and clinical scores.
METHODS
In a prospective, randomized, patient- and observer-blinded clinical study, 33 patients with primary osteoarthritis of the knee were included. All patients received a Genesis II total knee replacement. Sixteen patients received a mobile and 17 a fixed-bearing cruciate retaining Genesis II TKA. Clinical and quality-of-life scores, electromyography and gait analysis were applied preoperatively and postoperatively with a follow-up of 24 months.
RESULTS
In both groups, improvements from pre- to postoperative were detected. whereas the results of gait analysis and electromyography did not show any differences. The results from the clinical and the quality-of-life scores improved from pre- to postoperative, while the Knee Society Score showed a superiority of the mobile-bearing group (mean 159 ± 28) over the fixed-bearing group (mean 134 ± 41).
CONCLUSION
No functional advantage of mobile over fixed-bearing TKA was detected, although the mobile-bearing group had better clinical results for which a reason could not be found. These results only apply to cruciate retaining mobile-bearing TKA with a bearing which allows both rotation and anteroposterior translation. | 10.1007/s00167-011-1540-y |
pubmed_968_21089 | BACKGROUND
The modified thrombolysis in cerebral infarction (mTICI) scale is a widely used and validated qualitative tool to evaluate angiographic intracerebral inflow following endovascular thrombectomy (EVT). We validated a machine-learning (ML) algorithm to grade digital subtraction angiograms (DSA) using the mTICI scale.
MATERIALS AND METHODS
We included angiograms of identified middle cerebral artery (MCA) occlusions who underwent EVT. The complete DSA sequences were preprocessed and normalized. We created three convolutional neural networks to classify DSA into two outcomes, low- (mTICI 0,1,2a) and high-grade (mTICI 2b,2c,3).
RESULTS
We included a total of 234 angiograms in this study. The area under the receiver operating characteristic was 0.863 (95% CI 0.816-0.909), 0.914 (95% CI 0.876-0.951), and 0.890 (95% CI 0.848-0.932) for the anteroposterior (AP), lateral (L), and combined models, respectively, when dichotomizing outcomes into low and high grade. The models' area under the precision-recall curve was 0.879 (95% CI 0.829-0.930), 0.906 (95% CI 0.844-0.968), and 0.887 (95% CI 0.834-0.941) for the AP, L, and combined models.
CONCLUSION
In complete cerebral DSA, our angiography-based ML strategy was able to predict mTICI scores following EVT rapidly and reliably for MCA occlusions. | 10.1007/s00234-021-02851-3 |
pubmed_953_7161 | STUDY DESIGN
Single-site, exploratory, cross-sectional design.
OBJECTIVE
To identify variables associated with disability related to low back pain (LBP), as measured by the modified Oswestry Low Back Pain Disability Questionnaire (mOSW), in a sample of working adults with nonacute LBP.
BACKGROUND
Compared to acute LBP, there is little information available in the literature to identify variables associated with LBP-related disability in working individuals with stage 2 and stage 3 LBP.
METHODS
Data analyzed were from working individuals with nonacute LBP (n = 235). The response variable was dichotomized by mOSW score (less than 20 or 20 or greater), and the regressor variables included 27 self-report, sociodemographic, impairment-based, and kinematic measures used to assess individuals with LBP. Logistic regression was used to identify variables associated with mOSW.
RESULTS
One hundred eleven subjects had a mOSW score of 20 or greater, and 124 subjects had a mOSW score of less than 20. Logistic regression analysis identified 4 variables associated with LBP-related disability (mOSW): duration of LBP (P = .006), numeric pain rating (P<.0001), Fear-Avoidance Beliefs Questionnaire physical activity subscale (P = .0007), and limits of stability movement velocity in the forward direction (P = .02). The best model had an R2(u) of 0.25.
CONCLUSION
The odds of LBP-related disability (mOSW) in this sample of nonacute working individuals were found to increase with longer duration of LBP, higher numeric pain rating scores, higher Fear-Avoidance Beliefs Questionnaire physical activity subscale scores, and slower limits of stability movement velocity in the forward direction. The identification of limits of stability movement velocity is a novel finding that may support a link between sensorimotor balance deficits and disability in working individuals with nonacute LBP. | 10.2519/jospt.2013.4382 |
pubmed_247_10075 | A study was undertaken to determine the prevalence and risk factors for serological evidence of hepatitis C virus (HCV) infection in patients infected with the human immunodeficiency virus (HIV). Tests for anti-HCV antibody were carried out by enzyme-linked immunoassay (EIA) on 101 HIV-infected patients from two university-based outpatient clinics. Anti-HCV antibody reactive samples were tested by using a recombinant immunoblot assay (RIBA) for HCV antibodies. Fourteen of 101 (13.9%) HIV-infected patients were anti-HCV reactive by EIA. Of these 14, only seven were reactive by RIBA: four were intravenous drug users as a sole risk factor for HIV infection; and the remaining three acquired HIV by blood transfusion, contaminated instrument exposure or IV drug use and sexual contact. Acquisition of HIV by sexual activity alone was not associated with HCV infection. It is concluded that HCV infection is found in approximately 7% of a university HIV clinic population. False-positive anti-HCV antibody serology may lead to overestimation of the prevalence of HCV infection. Female sex and intravenous drug use are significantly associated with HCV infection among HIV-infected individuals. | 10.1002/jmv.1890330307 |
pubmed_205_16046 | Knowledge of the microbiology of pulmonary infections is critical for treatment of cystic fibrosis because sickness and mortality in this disease are mainly due to relapse occurring in the respiratory tract. The microbiology of pulmonary infections presents several singular aspects. Respiratory tract infections are caused by bacteria such as Staphylococcus aureus in the early years of life and Pseudomonas aeruginosa and Burkholderia cepacia thereafter. The patients, who are not immune compromised, are predisposed to chronic colonization and highly transmissible bacterial strains can cause cross-infections. Bacterial also develop resistance mechanisms which make them difficult to treat. Until recently the relationship between genetic defects and a predisposition to colonization was not noted, but recent studies have allowed us to form some interesting hypothesis. The present work analyzes the principal mechanisms of antibiotic resistance, with particular reference to classic cystic fibrosis pathogens, and looks at future prospects of respiratory tract infection treatment. | pubmed_205_16046 |
pubmed_882_4511 | PURPOSE
To evaluate change in quality of life (QoL) and symptoms in patients with lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH) in conditions of current clinical practice.
METHODS
Prospective, longitudinal, multicenter open-label study was carried out in urology outpatient clinics. Patients were ≥40 years of age with an International Prostate Symptom Score (IPSS) score ≥ 8. QoL and symptoms were measured at baseline and 6 months using the Benign Prostatic Hyperplasia Impact Index (BII) and the IPSS.
RESULTS
1713 patients were included for analysis. Mean (SD) IPSS and BII scores at baseline were 16.8 (5.4) and 6.8 (2.6), respectively. 8.9 % (n = 153) of study participants did not receive treatment (watchful waiting, WW), 70.3 % (n = 1204) were prescribed monotherapy (alpha-adrenergic blockers [AB]; phytotherapy [PT, of which 95.2 % was the hexanic extract of Serenoa repens, HESr]; or 5-alpha-reductase inhibitors [5ARI]), and 20.8 % (n = 356) received combined treatment (AB + 5ARI; AB + HESr; others). At 6 months, improvements in QoL were similar across the different medical treatment (MT) groups, both for monotherapy (AB: mean improvement [SD] of 2.4 points [2.4]; PT: 1.9 [2.4]; 5ARI: 2.5 [2.3]) and combined therapy (AB + 5ARI: 3.1 [2.9]; AB + PT: 3.1 [2.5]). There were no clinically significant differences between MT groups and all showed significant improvement over WW (p < 0.05). HESr showed similar efficacy to AB and 5ARI both as monotherapy and in combination with AB. Results on the IPSS were similar.
CONCLUSIONS
Improvements in QoL and symptoms were equivalent across the medical treatments most widely used in real-life practice to manage patients with moderate or severe LUTS. HESr showed an equivalent efficacy to AB and 5ARI with fewer side effects. | 10.1007/s11255-015-1206-7 |
pubmed_670_20794 | Classical work implied that early nematode embryogenesis is completely mosaic. This view was lately challenged by the demonstration that in C. elegans an early interaction has to occur to induce the production of muscle from a blastomere. Here, early embryonic blastomeres were inactivated by laser microsurgery. The cell lineages of irradiated embryos were compared to those of intact embryos. It is shown that one blastomere, MS, is required for the specification of mesodermal pharyngeal fates and another blastomere, P2, for the specification of hypodermal fates from the descendants of the AB blastomere, whereas the proper specification of the nervous system requires the presence of both. The irradiation of a third blastomere shows that interactions also occur within the ectoderm. I propose that the body plan of the C. elegans embryo may be established by two primary signals followed by secondary interactions. The suggested mechanisms are reminiscent of those involved in amphibian development. | 10.1016/0925-4773(91)90046-9 |
pubmed_688_15200 | Only 20 to 40% of the rural populations in Africa south of Sahara have the possibility to benefit from the classical health care. This situation interferes in the campaign against the main endemic diseases. Thus, in the efforts to control malaria, it appears necessary to get the population participation through the development of the primary health care services. Systematic chemotherapy of febrile attacks seems to be the easiest field strategy on a large way. The authors believe that such a strategy is possible through the development of primary health care services within the progressive decentralization of the health service network. | pubmed_688_15200 |
pubmed_311_14039 | EGb 761® (Tanakan®) is a standardized extract of Ginkgo biloba leaves that has demonstrated protective properties against neuronal and vascular damage. Overall, in randomized, placebo-controlled clinical trials and meta-analyses in adults with mild-to-moderate dementia, EGb 761® displayed positive effects, with changes from baseline in outcomes related to cognition, behaviour and global change that are generally better than those shown with placebo. EGb 761® is generally well tolerated, with no safety issues being identified during its many years of widespread use. | 10.1007/s40267-018-0537-8 |
pubmed_440_7192 | The detection of phosphate (Pi) under physiological conditions is a very important issue in environmental and biological sciences. Herein, a unique fluorescent probe {[EuL(H2O)1.35(DMF)0.65]·1.9DMF}n (1) was prepared through the organic-inorganic hybridization between asymmetrical tricarboxylate ligands and Eu2O2 clusters under solvothermal conditions. The as-prepared sample 1 exhibited excellent fluorescence properties and could be designed as a self-calibrating fluorescent probe for sensitively and selectively detecting Pi which served as an essential substance in aquatic ecosystems and biological systems. The different responses of the two emission peaks caused by the addition of Pi resulted in a continuous fluorescence color change, which could be clearly observed with the naked eye under UV light lamp illumination at 302 nm. Typically, a good linearity existed between the ratio of dual fluorescence intensities and the Pi contents ranging from 0.1 μM to 15 μM with a low detection limit of 52 nM (S/N = 3). It is noteworthy that the prepared self-calibrating fluorescent probe displayed specific recognition towards Pi anions with satisfactory recovery ranging from 92.8% to 100.6% in water samples and biological fluids. Thus, we can envision that this work may open a new avenue for the detection of many other bioactive ions in environmental and biological samples. | 10.1039/c8dt01515e |
pubmed_43_11044 | Essential protein plays a vital role in understanding the cellular life. With the advance in high-throughput technologies, a number of protein-protein interaction (PPI) networks have been constructed such that essential proteins can be identified from a system biology perspective. Although a series of network-based essential protein discovery methods have been proposed, these existing methods still have some drawbacks. Recently, it has been shown that the significance-based method SigEP is promising on overcoming the defects that are inherent in currently available essential protein identification methods. However, the SigEP method is developed under the unrealistic Erdös-Rényi (E-R) model and its time complexity is very high. Hence, we propose a new significance-based essential protein recognition method named EPCS in which the essential protein discovery problem is formulated as a community significance testing problem. Experimental results on four PPI networks show that EPCS performs better than nine state-of-the-art essential protein identification methods and the only significance-based essential protein identification method SigEP. | 10.1109/TCBB.2021.3102018 |
pubmed_1123_10130 | MicroRNAs (miRNAs) are a class of small molecules and non-coding single strand RNAs that regulate gene expression at the post-transcriptional level by binding to specific sequences within target genes. miRNAs have been recognized as important regulatory factors in organism development and disease expression. Some miRNAs regulate the proliferation and differentiation of osteoblasts, osteoclasts and chondrocytes, eventually influencing metabolism and bone formation. miRNAs are expected to provide potential gene therapy targets for the clinical treatment of metabolic bone diseases and bone injuries. Here, we review the recent research progress on the regulation of miRNAs in bone biology, with a particular focus on the miRNA-mediated control mechanisms of bone and cartilage formation. | 10.1016/j.bbrc.2012.01.075 |
pubmed_667_16435 | Ischemic diseases of heart and brain are the primary causes of mortality in industrialized nations. The ischemic injury with the consecutive reperfusion is responsible for the disturbance of microcirculation with ensuing tissue damage and organ dysfunction. Recent evidence suggests that oxygen-derived free radicals and activated polymorphonuclear leukocytes produced in ischemic tissue are instrumental in the development of ischemic cell injury. In pancreas, ischemia/ reperfusion is proposed as a potentially damaging factor accounting in part for the pathogenesis of acute pancreatitis. Apart from ischemia/reperfusion injury, the kallikrein-kinin system mediates acute inflammation associated with enhanced capillary permeability and accumulation of polymorphonuclear leukocytes, cardinal features of ischemia/reperfusion injury also in acute pancreatitis. Therefore, it seems reasonable to use bradykinin-antagonists to influence postischemic reperfusion injury of the pancreas. In the following, we describe the pathophysiology of ischemia/reperfusion injury with special reference to the pancreatic microcirculation and morphological changes as observed in a model of complete and reversible ischemia. Furthermore, we will discuss the effects of two bradykinin-antagonists (HOE 140 and CP-0597) on functional integrity of the pancreas after ischemia/ reperfusion. | 10.1002/(SICI)1097-0029(19970601)37:5/6<557::AID-JEMT16>3.0.CO;2-P |
pubmed_819_19362 | Pharmacists are the most accessible healthcare professional to many chronically ill patients and see patients with diabetes up to five times more often than any other healthcare provider. Besides this high accessibility, pharmacists have a strong focus on counseling, health education, and interaction with patients, making them ideal providers of diabetes education and valuable members of a multidisciplinary diabetes care team. Health education programs in general often have been developed without a basic theoretical framework. These programs are more difficult to evaluate in terms of how behavioral change may be best accomplished. Self-efficacy theory has been used in the past to develop successful patient education programs for patients with diabetes. The purpose of this paper is to describe self-efficacy theory and its role in diabetes education, and to encourage its use as a framework for the development of community pharmacy-based diabetes education programs. | 10.1177/014572179602200307 |
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