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pubmed_1082_6113 | Enzyme predigested poultry by-product meal made from onfarm, whole turkey mortality (E-TBM) was compared with soybean meal (SBM) and commercial poultry by-product meal (CPBM) in each of three experiments. In Experiment 1, young poults were fed diets containing 16, 20, or 24% CP with either SBM or E-TBM as protein sources. A separate group of poults was fed a nitrogen-free diet. The E-TBM was higher than SBM in protein, fat, lysine, methionine, and total sulfur amino acids. Diets containing E-TBM resulted in increased BW, feed consumption, and a higher protein efficiency ratio (PER) and net protein ratio (NPR) compared with diets containing SBM. In Experiment 2, feeding nonenzyme-treated turkey by-product (TBM) or E-TBM resulted in significantly improved BW and feed efficiency compared with CPBM but this may have been due to decreased protein in diets containing CPBM. Protein source did not affect feed intake, PER, NPR, or net protein utilization (NPU). In Experiment 3, the TMEn content of CPBM was lower than both TBM and E-TBM but lysine and methionine digestibilities were greater. | 10.3382/ps.0741180 |
pubmed_284_8023 | Azolimine, CL 90,748, an imidazolidinone, displayed the capacity to antagonize the effects of mineralocorticoids on renal electrolyte excretion in several animal models. Although large doses of azolimine produced natriuresis in adrenalectomized rats in the absence of exogenous mineralocorticoid, its effectiveness was greater in the presence of a steroid agonist. However, in conscious dogs given an infusion of saline plus dextrose, azolimine was only effective when desoxycorticosterone (DCA) was administered. The drug, therefore, may not be a pure competitive antagonist of mineralocorticoid, but its greater efficacy in the presence of mineralocorticoid distinguishes it from noncompetitive mineralocorticoid antagonists as amiloride and triamterene. Azolimine significantly improved the urinary Na/K ratio when used in combination with thiazides, furosemide and other classical diuretics both in adrenalectomized, desoxycorticosterone-treated rats and in sodium-deficient rats. | pubmed_284_8023 |
pubmed_687_2452 | The specific heats of saturated liquid ethane, C , have been measured at 106 temperatures in the temperature range 93 to 301 K. The specific heats at constant volume, C have been measured at 19 densities ranging from 0.2 to 3.1 times the critical density, at temperatures between 91 and 330 K, with pressures to 33 MPa, at 200 PVT states in all. The uncertainty of most of the measurements is estimated to be less than 2.0 percent. As the critical point is approached the uncertainty rises to about 5.0 percent. The measurements were performed to provide input data for accurate calculations of the thermodynamic properties for ethane. They are believed to be the most comprehensive specific heat measurements available for the liquid and vapor states of ethane. | 10.6028/jres.080A.069 |
pubmed_953_22002 | Standard serological tests have reached high levels of sensitivity and reproducibility but do not indicate whether infection is recent or long-standing. Among the 59960 sera analyzed for HIV positivity at the Retrovirus Laboratory, Operative Unit of Microbiology, Bologna, Italy, from January 2010 to July 2011, 134 samples showed an initial positive result. Application of the avidity test, able to distinguish between recent or long-standing HIV infection, classified 59 subjects as recently infected and 75 as chronically infected. Besides all the public health implications, the distinction between acute and chronic infection might serve to establish the time of infection and therefore reach any potential partners who might have been infected in a specific period of time. Although our results are limited to subjects referred to our laboratory and hence represent only a limited part of the problem, the routine application of methods able to distinguish recent from long-lasting infection could help monitor disease incidence, identify high-risk groups, and enhance epidemiological conclusions. | pubmed_953_22002 |
pubmed_431_126 | In 1988, Becker first described the "laser silicone flash" encountered while using the CO2 laser to remove breast siliconosis, but no subsequent use of the CO2 laser to remove siliconomas has been reported since. To our knowledge, lasers have not been described to treat facial silicone granulomas. Three cases of facial silicone granuloma (cheek, upper eyelids, and chin) were treated using the technique of CO2 laser vaporization.We describe a novel and effective method to remove facial siliconomas. This technique could avoid the need for radical resection of functional facial tissues such as nerves. Tiny globules of injected silicone in the face were vaporized without any untoward effects. Whether larger siliconomas can be treated in the same way remains to be seen and is an area of potential study. | 10.1097/SAP.0b013e318065c4e1 |
pubmed_408_14217 | Extended wear contact lenses are now a reality. Unfortunately, the physiological basis for their apparent success is less based on knowledge than wishful thinking. This paper discusses both what we know and what we don't know with the goal of giving the practitioner in the field a global view of this important and controversial procedure. | pubmed_408_14217 |
pubmed_74_14252 | Comparative effectiveness studies, referred to here as "usual-care" trials, seek to compare current medical practices for the same medical condition. Such studies are presumed to be safe and involve only minimal risks. However, that presumption may be flawed if the trial design contains "unusual" care, resulting in potential risks to subjects and inaccurately informed consent. Three case studies described here did not rely on clinical evidence to ascertain contemporaneous practice. As a result, the investigators drew inaccurate conclusions, misinformed research participants, and subjects' safety was compromised. Before approving usual-care protocols, IRBs and scientific review committees should evaluate the quality and completeness of information documenting usual-care practices. Guidance from governmental oversight agencies regarding evidence-based documentation of current clinical practice could prevent similar occurrences in future usual-care trials. Accurate information is necessary to ensure that trials comply with government regulations that require minimizing research risks to subjects and accurate informed consent documents. | 10.1080/15265161.2019.1687777 |
pubmed_916_7220 | BACKGROUND
High intake of fruit and vegetables as well as high plasma vitamin C concentrations have been associated with low risk of ischemic heart disease in prospective studies, but results from randomized clinical trials have been inconsistent.
OBJECTIVE
We tested the hypothesis that genetically high concentrations of plasma vitamin C, such as with high intake of fruit and vegetables, are associated with low risk of ischemic heart disease and all-cause mortality.
DESIGN
We used a Mendelian randomization approach and genotyped for solute carrier family 23 member 1 (SLC23A1) rs33972313 in the sodium-dependent vitamin C transporter 1 in 97,203 white individuals of whom 10,123 subjects had ischemic heart disease, and 8477 subjects died. We measured plasma vitamin C in 3512 individuals and included dietary information on 83,256 individuals.
RESULTS
The SLC23A1 rs33972313 G allele was associated with 11% higher plasma vitamin C. The multivariable adjusted HRs for highest compared with lowest fruit and vegetable intakes were 0.87 (95% CI: 0.78, 0.97; P = 0.01) for ischemic heart disease and 0.80 (95% CI: 0.73, 0.88; P < 0.001) for all-cause mortality. Corresponding HRs for rs33972313 GG (93%) compared with AA plus AG (7%) genotypes were 0.95 (95% CI: 0.88, 1.02; P = 0.21) and 0.96 (0.88, 1.03; P = 0.29), respectively. In an instrumental variable analysis, the OR for genetically determined 25% higher plasma vitamin C concentrations was 0.90 (95% CI: 0.75, 1.08; P = 0.27) for ischemic heart disease and 0.88 (0.72, 1.08; P = 0.22) for all-cause mortality.
CONCLUSIONS
High intake of fruit and vegetables was associated with low risk of ischemic heart disease and all-cause mortality. Although the 95% CI for genetically high plasma vitamin C concentrations overlapped 1.0, which made certain statistical inferences difficult, effect sizes were comparable to those for fruit and vegetable intake. Thus, judging by the effect size, our data cannot exclude that a favorable effect of high intake of fruit and vegetables could in part be driven by high vitamin C concentrations. | 10.3945/ajcn.114.104497 |
pubmed_755_5286 | The NIa proteinase encoded by tobacco etch potyvirus catalyzes six processing events, three of which occur by an autoproteolytic mechanism. Autoproteolysis is necessary to cleave the boundaries of both NIa and the 6-kDa protein, which is located adjacent to the N terminus of NIa in the viral polyprotein. As a consequence, NIa may exist in a free form or in a transient polyprotein form containing the 6-kDa protein. While the majority of NIa molecules localize to the nuclei of infected cells, a fraction of the NIa pool is attached covalently to the 5' terminus of genomic RNA in the cytoplasm. To determine whether the presence of the 6-kDa protein affects the nuclear transport properties of NIa, we have generated transgenic plants that express genes encoding a reporter enzyme, beta-glucuronidase (GUS), fused to NIa or NIa-containing polyproteins. The NIa/GUS fusion protein was detected by histochemical analysis in the nucleus. Similarly, an NIa/GUS fusion protein that arose by autoproteolysis of a 6-kDa/NIa/GUS polyprotein was found in the nucleus. In contrast, fusion protein consisting of 6-kDa/NIa/GUS, which failed to undergo proteolysis because of the presence of a Cys-to-Ala substitution in the proteolytic domain of NIa, was detected in the cytoplasm. The inhibition of NIa-mediated nuclear transport was not due to the Cys-to-Ala substitution, since this alteration had no effect on translocation in the absence of the 6-kDa protein. These results indicate that the 6-kDa protein impedes nuclear localization of NIa and suggest that subcellular transport of NIa may be regulated by autoproteolysis. | 10.1128/JVI.66.9.5662-5666.1992 |
pubmed_733_11766 | Nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand for the G(i)-coupled N/OFQ receptor (NOP). We have examined the effects of chronic exposure of Chinese hamster ovary cells expressing the recombinant human NOP receptor (CHO(hNOP)) to 1 nM N/OFQ for up to 48 h in the absence and presence of the NOP selective antagonist [Nphe(1)]N/OFQ (1-13)NH(2) ([Nphe(1)]). Then, either a concentration-response curve for N/OFQ inhibition of cAMP formation was constructed or the cells were homogenized and membrane receptor density was determined using [(125)I]Y(14)N/OFQ. There was a time-dependent reduction in pEC(50) (without a change in maximum) for N/OFQ with significant differences observed following >24 h of exposure (control pEC(50) approximately 9.5; 48 h pretreatment approximately 8.7). In cells co-exposed to N/OFQ+[Nphe(1)] for 48 h, there was no reduction in pEC(50). There was a compensatory (approximately 2.5-fold), [Nphe(1)]-sensitive increase in cAMP mass in cells exposed to N/OFQ for 24-48 h. N/OFQ pretreatment also resulted in a time-dependent [Nphe(1)]-sensitive loss of cell surface receptors. At 48 h, B(max) was reduced from approximately 2.0 to approximately 1.3 pmol mg(-1) protein without a change in pK(d) for N/OFQ. There was a positive correlation between pEC(50) for cAMP inhibition and B(max). The lack of effect on maximum cAMP response probably results from receptor overexpression and the creation of a receptor reserve. | 10.1016/s0014-2999(02)01606-0 |
pubmed_1138_8543 | This study examined the influence of a provocative dynamic exercise maneuver on nerve conduction studies (NCS) in three study groups: Group A, controls (n = 10); Group B, patients with clinical carpal tunnel syndrome (CTS), but normal NCS (n = 10); and Group C, patients with clinical CTS and abnormal NCS (n = 10). A wrist flexion-extension exercise was designed to increase pressure on the median nerve within the carpal tunnel to aid diagnosis by revealing latent nerve conduction slowing in patients presenting with clinical CTS but normal NCS. The exercise protocol was sufficient to evoke symptom exacerbation in 50% of the patients. The results showed that 4 minutes of this active provocative maneuver revealed a significant (p < .05) difference in the sensory distal latency (median) for digit IV; however, this was not clinically significant inasmuch as the change in latency was insufficient to meet the a priori criteria for NCS abnormality required for the electrodiagnosis of median nerve abnormality. There was no increase in the distal sensory latencies of those patients whose symptoms were exacerbated, when compared with those patients whose symptoms remained unchanged. There appears little diagnostic value in adding this particular active provocative wrist maneuver to the routine electrodiagnostic evaluation for carpal tunnel syndrome. | pubmed_1138_8543 |
pubmed_908_3475 | Principal component analysis enables dimensional reduction of multivariate datasets that are typical in high-content screening. A common analysis utilizing principal components is a distance measurement between a perturbagen-such as small-molecule treatment or shRNA knockdown-and a negative control. This method works well to identify active perturbagens, though it cannot discern between distinct phenotypic responses. Here, we describe an extension of the principal component analysis approach to multivariate high-content screening data to enable quantification of differences in direction in principal component space. The theta comparative cell scoring method can identify and quantify differential phenotypic responses between panels of cell lines to small-molecule treatment to support in vitro pharmacogenomics and drug mechanism-of-action studies. | 10.1007/978-1-4939-7847-2_13 |
pubmed_500_9290 | Modern judicial activism--establishing caselaw that functions as law until statutes are subsequently enacted--has been the hallmark of the variety of legal issues surrounding the HIV condition and AIDS diseases. Most federal and state courts have been compelled to resolve many HIV/AIDS-related controversies in advance of legislative guidance and have generally done so by protecting the civil rights of persons with HIV/AIDS under established law as well as the traditions of Western law. | pubmed_500_9290 |
pubmed_179_20161 | BACKGROUND
COVID-19 was first detected in Malaysia on 25 January 2020. Multiple clusters were detected in Petaling District, with the first locally transmitted case reported on 8 February. Descriptive analyses of the epidemiology of the COVID-19 outbreak in Petaling are presented, from the first case to the end of the first wave.
METHODS
All laboratory-confirmed COVID-19 cases reported to the Petaling District Health Office between 1 February and 26 June 2020 were analysed. Socio-demographic characteristics, symptoms, date of onset, date of exposure, travel history and history of comorbidities were obtained by phone interviews using one of two investigation forms. The descriptive analysis was conducted according to time, place and person.
RESULTS
There were 437 COVID-19 cases, for an incidence rate of 24/100 000 population. Ten (2.3%) deaths and 427 recovered cases were recorded. Of the 437 cases, 35.5% remained asymptomatic and 64.5% were symptomatic. Common symptoms included fever (43.8%), cough (31.6%) and sore throat (16.2%); 67.3% had no comorbidities, 62.5% reported close contact with a confirmed case, and 76.7% were local infections. Transmission occurred in four main groups: religious gatherings (20.4%), corporations (15.1%), health facilities (10.3%) and a wholesale wet market (6.4%). In 31.9% of confirmed cases, an epidemiological link to an asymptomatic case was found.
CONCLUSION
Transmission of the disease by asymptomatic cases should be emphasized to ensure continuous wearing of face masks, hand hygiene and social distancing. Further research should be conducted to better understand the transmission of SARS-CoV-2 from asymptomatic cases. | 10.5365/wpsar.2020.11.4.001 |
pubmed_100_563 | The overall aim of this study was to examine obesogenic factors in children from single and dual parent families. Data from the Longitudinal Study of Australian Children (LSAC) (8,717 children) were analyzed to examine the differences in children's activity levels, dietary intake and BMI according to parental status and determine the likelihood of childhood overweight and obesity in a single-parent household. There were higher rates of overweight and obesity in girls aged four to nine whose parents were single (OR 1:60). Children in single-parent households watched more television, ate more food high in fat and sugar and less fresh fruit and vegetables than children from dual-parent households. The findings suggested that an additive effect of dietary and activity variables may contribute to the higher rates of overweight and obesity in Australian children, and that girls from single-parent households may be particularly at risk. | 10.3109/17477166.2011.598938 |
pubmed_204_21473 | We have developed a highly convergent synthesis of the manumycin-type m-C7N-antibiotic nisamycin that is applicable to other members of this family of antibiotics. The synthesis features a three-step sequence to the epoxyquinol core that serves as a scaffold for the attachment of the polyene side chains. The eastern polyene side chain was constructed via a novel organozirconocene-mediated synthesis. Zirconocene methodology was also applied to the synthesis of the polyene side chains of asukamycin. The southern side chain of nisamycin was introduced via a Stille reaction that employed a vinyl bromo ketone, derived from an acid-sensitive bromo ketal. Pd-mediated coupling of the vinyl bromide with a stannyl TIPS ester gave TIPS-protected nisamycin that was readily converted to the natural product. | 10.1021/jo990413m |
pubmed_509_12616 | BACKGROUND
Regadenoson during exercise stress test (ETT) can provide maximal hyperemia for myocardial perfusion imaging (MPI), along with exercise information. Our aim was to study the feasibility and safety of regadenoson injection at peak ETT for submaximal heart rate (HR) response.
METHODS
Consecutive patients who underwent SPECT MPI with standard Bruce ETT or supine-regadenoson (Supine-Reg) were analyzed. ETT patients were grouped as ETT-Max [maximal HR > 0.85 * (220 - age), N = 1,522], ETT-Submax (submaximal HR no regadenoson, N = 504), ETT-Reg (submaximal HR and regadenoson, N = 211).
RESULTS
The HR during ETT was submaximal in 715 (32%) patients. Of these, 211 patients (30%) underwent ETT-Reg (mean exercise duration: 5.5 ± 2.5 minutes). ETT-Reg patients had a higher frequency of hypertension, diabetes, smoking and beta-blocker use, similar rest systolic blood pressure (SBP), but lower rest and peak HR and peak SBP compared to ETT-Max patients. There were no serious complications with regadenoson. Side effects (49% vs 6%, P < .0001) were fewer and aminophylline use was lower with ETT-Reg compared to Supine-Reg (0.5% vs 8.1%, P = .001).
CONCLUSIONS
Submaximal HR response to ETT is common. ETT-Reg is safe, feasible, and well-tolerated. ETT-Reg facilitates a diagnostic MPI with reporting of functional capacity, exercise ECG/hemodynamic changes and MPI at maximal hyperemia. | 10.1007/s12350-012-9562-5 |
pubmed_737_243 | UNLABELLED
PREMISE OF THE STUDY
Microsatellite loci were isolated and characterized from enriched genomic libraries of two taxa of the Chilean Epipetrum group of Dioscorea to assess their levels of genetic diversity and population differentiation. •
METHODS AND RESULTS
Eleven microsatellite loci were identified. Six out of nine microsatellites from D. biloba amplified in D. humilis, and the two microsatellites from D. humilis amplified in both taxa. Two different sets of eight loci amplified in each of the two tested taxa, D. biloba and D. humilis. The average number of alleles was 5.75 and 5 for D. biloba and D. humilis, respectively. Higher levels of mean genetic diversity were found in D. biloba (H(E) = 0.639) than in D. humilis (H(E) = 0.414). •
CONCLUSIONS
These microsatellite primers will be useful in population genetic studies and to establish conservation strategies in the endangered taxa of the Epipetrum group of Dioscorea. | 10.3732/ajb.1000304 |
pubmed_42_2771 | Membrane proteins transported to the yeast vacuole can have two fates. Some reach the outer vacuolar membrane, whereas others enter internal vesicles, which form in late endosomes, and are ultimately degraded. The vacuolar SNAREs Nyv1p and Vam3p avoid this fate by using the AP-3-dependent pathway, which bypasses late endosomes, but the endosomal SNARE Pep12p must avoid it more directly. Deletion analysis revealed no cytoplasmic sequences necessary to prevent the internalization of Pep12p in endosomes. However, introduction of acidic residues into the cytoplasmic half of the transmembrane domain created a dominant internalization signal. In other contexts, this same feature diverted proteins from the Golgi to endosomes and slowed their exit from the endoplasmic reticulum. The more modestly polar transmembrane domains of Sec12p and Ufe1p, which normally serve to hold these proteins in the endoplasmic reticulum, also cause Pep12p to be internalized, as does that of the vacuolar protein Cps1p. It seems that quality control mechanisms recognize polar transmembrane domains at multiple points in the secretory and endocytic pathways and in endosomes sort proteins for subsequent destruction in the vacuole. These mechanisms may minimize the damaging effects of abnormally exposed polar residues while being exploited for the localization of some normal proteins. | 10.1091/mbc.11.11.3737 |
pubmed_278_18686 | OBJECTIVE
To assess the utility of the neutrophil-to-lymphocyte ratio (NLR) in predicting outcome in canine pneumonia compared with routine hematological parameters and systemic inflammatory response syndrome (SIRS) scores.
DESIGN
Retrospective study.
SETTING
University teaching hospital.
ANIMALS
Forty-nine client-owned dogs.
INTERVENTIONS
None MEASUREMENTS AND MAIN RESULTS: Medical records were reviewed to identify dogs with a diagnosis of pneumonia from July 2011 to December 2016. Signalment, clinical findings, laboratory characteristics, and outcome were recorded. Inclusion criteria were a clinical and radiographic diagnosis of pneumonia, plus reference laboratory hematology at diagnosis. Cases that received steroids were excluded. Euthanized dogs were only included in statistical analysis if euthanized solely due to pneumonia severity. The NLR, total WBC count, neutrophil count, lymphocyte count, band neutrophil percent of total WBC count (%-bands), and percentage of cases diagnosed with SIRS were compared between survivors and nonsurvivors. Receiver operating characteristic curves were generated to identify optimal sensitivity and specificity cutoffs for nonsurvival to discharge. Two hundred records were retrieved; 49 cases fulfilled the inclusion criteria. Of these, 33 (67%) survived to discharge. The NLR did not differ significantly between the survivors and nonsurvivors, nor did total WBC count or neutrophil count. Survivors had a significantly lower %-bands than nonsurvivors (P < 0.001) and higher lymphocyte count (P = 0.004). The mortality rate did not differ significantly between dogs with and without SIRS. Receiver operating characteristic analysis identified a %-bands cutoff of 2.5% or higher had an 83% sensitivity and 79% specificity for nonsurvival.
CONCLUSIONS
Unlike in human medicine, neither NLR nor SIRS scores predicted outcome in this cohort of dogs with pneumonia. However, survivors had a lower %-bands and higher lymphocyte count than nonsurvivors, which may be helpful prognostically in clinical cases. | 10.1111/vec.13067 |
pubmed_1069_6293 | The work is based on the author's clinical experience gained due to her responsibilities as a consultant in the Department of Occupational Diseases, Nofer Institute of Occupational Medicine, Lodz, as well as on the literature dealing with the effect of some chemical and physical occupational hazards on the central nervous system. The author points out that psychological examinations play a significant role in diagnosis and prevention of occupational disease. She suggests that workers should be subjected to periodical psychological examinations during the whole period of employment. Particular indications for these examinations are also discussed. | pubmed_1069_6293 |
pubmed_642_14747 | BACKGROUND
We sought to compare clinical outcomes of concomitant cholecystectomy during four different types of bariatric surgery vs. bariatric surgery alone.
DATA SOURCES
A systematic literature search of PubMed and Cochrane databases was conducted in accordance with the PRISMA guidelines. Thirty studies were included in this study, reporting data on 13,675 patients. Our findings suggest a higher rate of anastomotic leak/stricture in the case of concomitant cholecystectomy with gastric bypass compared to those who had gastric bypass alone. The scarcity of data concerning sleeve gastrectomy, adjustable gastric banding and biliopancreatic diversion prevented us from quantifying possible difference of outcomes between the examined treatment groups.
CONCLUSIONS
This study highlights the small number and poor quality of available studies referring to the role of simultaneous cholecystectomy during bariatric surgery. | 10.1016/j.amjsurg.2019.02.006 |
pubmed_1070_5214 | OBJECTIVE
To identify factors that influenced medical students at Monash University to undertake their first year of clinical training (third year of the medical course) at a rural clinical school (RCS).
DESIGN
Third-year Monash University medical students undertaking clinical placements at a RCS were surveyed in 2005. A semistructured questionnaire was used to ask students to rate the influence of a list of factors on their decision to undertake their year-long placement at a RCS.
RESULTS
Under half (48%) of students studying at an RCS reported that they were of rural background. All surveyed items were identified as having had a positive influence. Greater clinical experience, learning opportunities and patient access were identified as having the greatest positive influence followed closely by free accommodation and other financial and supportive incentives. Future rural career intention was eight times more likely to be a positive influence in rural compared with urban background students.
CONCLUSION
The most important positive influence on Monash third-year medical students' decision to study at an RCS is the perception of high-quality clinical experiences and education. This perception arises from rural exposure during pre-clinical years. | 10.1111/j.1440-1584.2008.00978.x |
pubmed_959_17713 | Cellular contacts modify the way cells migrate in a cohesive group with respect to a free single cell. The resulting motion is persistent and correlated, with cells' velocities self-aligning in time. The presence of a dense agglomerate of cells makes the application of single particle tracking techniques to define cells dynamics difficult, especially in the case of phase contrast images. Here, we propose an original pipeline for the analysis of phase contrast images of the wound healing scratch assay acquired in time-lapse, with the aim of extracting single particle trajectories describing the dynamics of the wound closure. In such an approach, the membrane of the cells at the border of the wound is taken as a unicum, i.e., the wound edge, and the dynamics is described by the stochastic motion of an ensemble of points on such a membrane, i.e., pseudo-particles. For each single frame, the pipeline of analysis includes: first, a texture classification for separating the background from the cells and for identifying the wound edge; second, the computation of the coordinates of the ensemble of pseudo-particles, chosen to be uniformly distributed along the length of the wound edge. We show the results of this method applied to a glioma cell line (T98G) performing a wound healing scratch assay without external stimuli. We discuss the efficiency of the method to assess cell motility and possible applications to other experimental layouts, such as single cell motion. The pipeline is developed in the Python language and is available upon request. | 10.3390/e23030284 |
pubmed_579_16977 | Emerging evidence shows that hydrocarbonoclastic bacteria (HCB) may be commonly found associated with phytoplankton in the ocean, but the ecology of these bacteria and how they respond to crude oil remains poorly understood. Here, we used a natural diatom-bacterial assemblage to investigate the diversity and response of HCB associated with a cosmopolitan marine diatom, Skeletonema costatum, to crude oil. Pyrosequencing analysis and qPCR revealed a dramatic transition in the diatom-associated bacterial community, defined initially by a short-lived bloom of Methylophaga (putative oil degraders) that was subsequently succeeded by distinct groups of HCB (Marinobacter, Polycyclovorans, Arenibacter, Parvibaculum, Roseobacter clade), including putative novel phyla, as well as other groups with previously unqualified oil-degrading potential. Interestingly, these oil-enriched organisms contributed to the apparent and exclusive biodegradation of substituted and non-substituted polycyclic aromatic hydrocarbons (PAHs), thereby suggesting that the HCB community associated with the diatom is tuned to specializing in the degradation of PAHs. Furthermore, the formation of marine oil snow (MOS) in oil-amended incubations was consistent with its formation during the Deepwater Horizon oil spill. This work highlights the phycosphere of phytoplankton as an underexplored biotope in the ocean where HCB may contribute importantly to the biodegradation of hydrocarbon contaminants in marine surface waters. | 10.1111/1462-2920.12988 |
pubmed_64_17003 | Power plants are considered as the major source of carbon dioxide pollution in Kuwait. The gas is released from the combustion of fuel with air to convert water into steam. It has been proven that the use of enriched oxygen can reduce fuel consumption and minimize emissions. In this study, UniSim (Honeywell, Charlotte, NC, USA) was used to estimate the fuel savings and carbon dioxide emissions of the largest power plant in Kuwait (Alzour). Results showed that at 30 mol% oxygen, the fuel consumption was lowered by 8%, with a reduction in carbon dioxide emissions by 3524 tons per day. An economic analysis was performed on the use of a membrane unit to produce 30 mol% oxygen. At current market prices, the unit is not economical. However, the system can achieve a payback duration of 3 years if natural gas price increases to USD 6.74 or the compressor cost decreases to USD 52 per kW. Currently, the research and development sector is targeting a membrane fabrication cost of less than USD 10 per m2 to make the membrane process more attractive. | 10.3390/membranes11030211 |
pubmed_786_6535 | While the role of the mutated Huntington's disease (HD) protein in the pathogenesis of HD has been the focus of intensive investigation, the normal protein has received less attention. Nonetheless, the wild-type HD protein appears to be essential for embryogenesis, since deletion of the HD gene in mice results in early embryonic lethality. This early lethality is due to a critical role the HD protein, called huntingtin (Htt), plays in extraembryonic membrane function, presumably in vesicular transport of nutrients. Studies of mutant mice expressing low levels of Htt and of chimeric mice generated by blastocyst injection of Hdh-/- embryonic stem cells show that wildtype Htt plays an important role later in development as well, specifically in forebrain formation. Moreover, various lines of study suggest that normal Htt is also critical for survival of neurons in the adult forebrain. The observation that Htt plays its key developmental and survival roles in those brain areas most affected in HD raises the possibility that a subtle loss of function on the part of the mutant protein or a sequestering of wild-type Htt by mutant Htt may contribute to HD pathogenesis. Regardless of whether this is so, the prosurvival role of Htt suggests that HD therapies that block production of both wild-type and mutant Htt may themselves be harmful. | 10.1385/MN:28:3:259 |
pubmed_780_9773 | A 34 year-old female presented with blood-stained pleural effusion and ascites. Investigation revealed a pelvic mass. She underwent exploratory laparotomy, and was found to have endometriosis. Total abdominal hysterectomy and right salpingo-oophorectomy was performed. | 10.1007/pl00007484 |
pubmed_752_4972 | Dioxaborines dyes, based on the OBO atomic sequence, constitute one promising series of molecules for both organic electronics and bioimaging applications. Using Time-Dependent Density Functional Theory, we have simulated the optical signatures of these fluoroborates. In particular, we have computed the 0-0 energies and shapes of both the absorption and the emission bands. To assess the importance of solvent effects three polarization schemes have been applied within the Polarizable Continuum Model: the linear-response (LR), the corrected linear-response (cLR), and the state-specific (SS). We show that the SS approach is unable to yield consistent chemical trends for these challenging compounds that combine charge-transfer and cyanine characters. On the contrary, LR and cLR are more effective in reproducing chemical trends in OBO dyes. We have applied our computational protocol not only to analyze the signatures of existing dyes but also to design structures with red-shifted absorption and emission bands. | 10.1021/ct4009848 |
pubmed_56_21537 | Hydrogels consisting of three-dimensional (3D) polymeric networks have found a wide range of applications in biotechnology due to their large water capacity, high biocompatibility, and facile functional versatility. The hydrogels with stimulus-responsive swelling properties have been particularly instrumental to realizing signal transduction in biosensors and bioelectronics. Graphenes are two-dimensional (2D) nanomaterials with unprecedented physical, optical, and electronic properties and have also found many applications in biosensors and bioelectronics. These two classes of materials present complementary strengths and limitations which, when effectively coupled, can result in significant synergism in their electrical, mechanical, and biocompatible properties. This report reviews recent advances made with hydrogel and graphene materials for the development of high-performance bioelectronics devices. The report focuses on the interesting intersection of these materials wherein 2D graphenes are hybridized with 3D hydrogels to develop the next generation biosensors and bioelectronics. | 10.1016/j.bios.2016.03.045 |
pubmed_583_5071 | Shortages of health care professionals have plagued rural areas of the USA for more than a century. Programs to alleviate them have met with limited success. These programs generally focus on factors that affect recruitment and retention, with the supposition that poor recruitment drives most shortages. The strongest known influence on rural physician recruitment is a "rural upbringing," but little is known about how this childhood experience promotes a return to rural areas, or how non-rural physicians choose rural practice without such an upbringing. Less is known about how rural upbringing affects retention. Through twenty-two in-depth, semi-structured interviews with both rural- and urban-raised physicians in northeastern California and northwestern Nevada, this study investigates practice location choice over the life course, describing a progression of events and experiences important to rural practice choice and retention in both groups. Study results suggest that rural exposure via education, recreation, or upbringing facilitates future rural practice through four major pathways. Desires for familiarity, sense of place, community involvement, and self-actualization were the major motivations for initial and continuing small-town residence choice. A history of strong community or geographic ties, either urban or rural, also encouraged initial rural practice. Finally, prior resilience under adverse circumstances was predictive of continued retention in the face of adversity. Physicians' decisions to stay or leave exhibited a cost-benefit pattern once their basic needs were met. These results support a focus on recruitment of both rural-raised and community-oriented applicants to medical school, residency, and rural practice. Local mentorship and "place-specific education" can support the integration of new rural physicians by promoting self-actualization, community integration, sense of place, and resilience. Health policy efforts to improve the physician workforce must address these complexities in order to support the variety of physicians who choose and remain in rural practice. | 10.1016/j.socscimed.2009.08.002 |
pubmed_186_11559 | OBJECTIVE
To review the efficacy of current treatment options for adults with obstructive sleep apnea (OSA).
METHODS
Review of the literature.
RESULTS
OSA, characterized by repetitive ≥ 10-second interruptions (apnea) or reductions (hypopnea) in airflow, is initiated by partial or complete collapse in the upper airway despite respiratory effort. When left untreated, OSA is associated with comorbid conditions, such as cardiovascular and metabolic diseases. The current "gold standard" treatment for OSA is continuous positive air pressure (CPAP), which pneumatically stabilizes the upper airways. CPAP has proven efficacy and potential cost savings via decreases in health comorbidities and/or motor-vehicle crashes. However, CPAP treatment is not well-tolerated due to various side effects, and adherence among OSA subjects can be as low as 50% in certain populations. Other treatment options for OSA include improving CPAP tolerability, increasing CPAP adherence through patient interventions, weight loss/exercise, positional therapy, nasal expiratory positive airway pressure, oral pressure therapy, oral appliances, surgery, hypoglossal nerve stimulation, drug treatment, and combining 2 or more of the aforementioned treatments. Despite the many options available to treat OSA, none of them are as efficacious as CPAP. However, many of these treatments are tolerable, and adherence rates are higher than those of the CPAP, making them a more viable treatment option for long-term use.
CONCLUSION
Patients need to weigh the benefits and risks of available treatments for OSA. More large randomized controlled studies on treatments or combination of treatments for OSA are needed that measure parameters such as treatment adherence, apnea-hypopnea index, oxygen desaturation, subjective sleepiness, quality of life, and adverse events. | pubmed_186_11559 |
pubmed_862_15130 | The ubiquitylation of membrane proteins destined for the vacuole/lysosome is essential for their recognition by the endosomal sorting machinery and their internalization into vesicles of multivesicular bodies (MVBs). In yeast, this process requires Rsp5p, an essential ubiquitin ligase of the Nedd4 family. We describe here two redundant proteins, Ear1p and Ssh4p, required for the vacuolar targeting of several cargoes originating from the Golgi or the plasma membrane. Ear1p is an endosomal protein that interacts with Rsp5p through its PPxY motifs, and it is required for the ubiquitylation of selected cargoes before their MVB sorting. In-frame fusion of cargo to ubiquitin overcomes the need for Ear1p/Ssh4p, confirming a role for these proteins in cargo ubiquitylation. Interestingly, Ear1p is itself ubiquitylated by Rsp5p and targeted to the vacuole. Finally, Ear1p overexpression leads to Rsp5p accumulation at endosomes, interfering with some of its functions in trafficking. Therefore, Ear1p/Ssh4p recruit Rsp5p and assist it in its function at MVBs by directing the ubiquitylation of specific cargoes. | 10.1091/mbc.E08-01-0068 |
pubmed_422_5477 | The origin, history, and singularity of our species has fascinated storytellers, philosophers and scientists throughout, and doubtless before, recorded history. Anthropology, the modern-era discipline that deals with these issues, is a notoriously contentious field, perhaps because the topic at hand - the nature of our own species - is one that is difficult or impossible to approach in an unbiased way. Recently, molecular genetics has increasingly contributed to this field. Here, I briefly discuss three areas where I believe molecular studies are likely to be of decisive importance in the future. These concern the questions of where and when our species originated, what the genetic background for characters that differ between us and apes is, and how the phenotypic traits that vary among human groups have evolved. | pubmed_422_5477 |
pubmed_128_16176 | In the treatment of postpartum haemorrhage from uterine atony, uterine compression sutures, such as the B-Lynch suture and its modifications have a role with the advantage of preservation of the uterus for fertility. There is however, a risk that apposition of the anterior and posterior walls of the uterus will impede drainage of lochia, resulting in undesirable complications. We undertook a five-year retrospective study of all women who underwent uterine compression sutures at the KK Women's and Children's Hospital, between 2008 and 2012. In total, 23 women had uterine compression sutures during the study period, of which, nineteen women managed to conserve their uterus. Our complication rate was 25%, which included persistent vaginal discharge, pyometra and endometritis. There were three conceptions, with two successful pregnancies. Our study shows uterine compression suture to be a safe and effective alternative to avoid hysterectomy with preservation of fertility at the time of major postpartum haemorrhage. The outcome of subsequent pregnancies is reassuring. | 10.3109/01443615.2014.895309 |
pubmed_819_18978 | The objective of this study was to characterize a site at which it is likely that melatonin mediates photoperiodic control of reproduction in the male Syrian hamster. The first experiment was a comparison of the distributions of iodomelatonin (IMEL)-binding sites and cells immunoreactive to androgen receptors (AR-ir) in the medio-basal hypothalamus (MBH). AR-ir cells extended throughout the MBH, whereas IMEL binding was restricted to the dorsomedial nucleus (DMN). Comparisons between IMEL binding and AR-ir on adjacent cryostat sections revealed a clear overlap between the IMEL-binding sites and a distinct subpopulation of AR-ir cells within the DMN. The second experiment examined whether lesions of these IMEL- and androgen-responsive cells affected the response of the hamsters to short-day (SD)-like infusions of melatonin. Animals received sham or bilateral electrolytic lesions of the IMEL-binding sites within the DMN of the hypothalamus (MBH-X). Animals were pinealectomized and 4 wk later fitted with an s.c. cannula for the daily infusion of either melatonin (50 ng/h) or saline (500 microliters/10 h). After 6 wk the animals with sham lesions showed gonadal atrophy and lower serum concentrations of LH and prolactin (PRL) after infusions with melatonin. In contrast, MBH-X animals given melatonin had large testes and long-day (LD)-like serum LH concentrations. Infusions of melatonin did, however, cause a significant decline in serum PRL level. This study shows that an intact MBH is essential for the expression of gonadotrophic but not lactotrophic responses to melatonin and/or photoperiod. It also suggests that cells responsive to both gondal steroids and melatonin may be involved in the seasonal variation in GnRH release, and indicates a site at which melatonin might influence sensitivity to steroid feedback, a hypothalamic function known to be regulated by photoperiod. | 10.1095/biolreprod54.2.470 |
pubmed_796_5659 | This study was designed to address three specific questions in human B cells. First, to determine whether transforming growth factor-beta (TGF-beta)2 has similar biologic effects on B cell function as does TGF-beta 1. Second, to test the hypothesis that TGF-beta 1 is an autocrine growth and differentiation inhibitor. Finally, because multiple receptor species for TGF-beta have been identified on other cell types, to determine by chemical cross-linking and competitive binding studies the nature of the TGF-beta 1 R present on normal and transformed B cells. Exogenous TGF-beta 2 was found to be functionally similar to TGF-beta 1 in its inhibition of factor dependent normal B cell proliferation and Ig secretion. When an antibody, specific for the active form of TGF-beta 1, was added in conjunction with IL-2 to previously stimulated B cell cultures, there was a 14.4 +/- 4.2% increase in B cell proliferation, a 22 +/- 6% increase in IgG production, and a 33 +/- 8.6% increase in IgM production when compared to control cultures. Chemical cross-linking of 125I-TGF-beta 1 to normal B cell membranes identified two major cross-linked species of 65 and 90 kDa. A fivefold excess of unlabeled TGF-beta 1 competitively inhibited the detection of both of these bands while a 50-fold excess of unlabeled TGF-beta 2 did not inhibit the 90-kDa band and only partially inhibited (60%) of the 65-kDa band. Chemical cross-linking of 125I-TGF-beta 1 to transformed B cell membranes identified only a single band of 60 kDa. Scatchard plot analysis of 125I-TGF-beta 1 binding to normal B cells that was competitively inhibited with increasing concentrations of unlabeled TGF-beta 1 revealed both high and low affinity binding sites whereas analysis of 125I-TGF-beta 1 binding in the presence of increasing concentrations of unlabeled TGF-beta 2 revealed only low affinity sites. These findings demonstrate that TGF-beta 2 is as effective as TGF-beta 1 in inhibiting human B cell function, that small amounts of active TGF-beta 1 are present endogenously in in vitro cultures which partially inhibit B cell function, that two major TGF-beta 1 R cross-linked complexes of 65 and 90 kDa are present on normal B cells, and that transformation of B cells may be accompanied by changes in the TGF-beta 1 R. | pubmed_796_5659 |
pubmed_326_17706 | This study investigated the effect of propofol on the pulmonary vascular bed of the rat. Propofol (5 x 10(-6) to 5 x 10(-4) M) did not alter the basal perfusion pressure in isolated rat lungs perfused at a constant flow (0.03 mL g body wt-1 min-1) with Krebs-Henseleit solution. When perfusion pressure was elevated by raising the K+ concentration to 30 mM (depolarizing Krebs-Henseleit solution), propofol decreased it in a concentration-dependent manner. Indomethacin (3 x 10(-6) M) and NG-nitro-L-arginine methyl ester (10(-4) M) did not affect the response to propofol, which excluded the role of cyclo-oxygenase metabolites and nitric oxide, respectively. The ATP-sensitive K+ (K+ATP) channel blocker glibenclamide (3 x 10(-6) and 10(-5) M) inhibited the vasodilator effect of propofol. When lungs were perfused with Ca(2+)-free depolarizing Krebs-Henseleit solution, 0.1-2.5 mM Ca+2 produced a concentration-dependent pressor response. Propofol (5 x 10(-5) M) attenuated the vasopressor response to Ca2+ significantly. In conclusion, the activation of K+ATP channels is probably the major mechanism of the vasodilator effect of propofol, at clinically relevant concentrations, in the rat lung. The Ca2+ antagonistic property of propofol is evident only at higher concentrations. | pubmed_326_17706 |
pubmed_156_4283 | Prior to the implementation of the nationwide toll-free telephone number, most poison centers already provided toll-free service; therefore, the impact of toll-free access to a poison center on call volume is difficult to assess in the majority of poison centers. This analysis examined the effect that the new nationwide toll-free telephone number had on total call volume (exposures and information calls) in a poison center without previous toll-free access and serving a large urban and rural population. All calls received by a Regional Poison Information Center (RPIC) over a consecutive 27-mo period (2000, 2001, Jan-Jun 2002) were analyzed. April 2001 was the first full month of toll-free service. Data from January-March and January-June for 2000, 2001 and 2002 served as 3 and 6-mo benchmark and study periods. The 3 and 6-mo periods for each of the 3 years were used to conduct comparative trend analysis. Over 1.1 million pieces of literature and sheets of stickers that contained the toll-free number were distributed throughout the region over the study period. Use of the toll-free number increased from 590 calls in July 2001 to 2,157 in June 2002. Total call volume increased by 11.2%. Trend analysis revealed a 9.9% increase in exposure volume when comparing 2001 and 2002 data. There was a significant increase in utilization of the toll-free number for information purposes from people residing in rural counties. Toll-free access to the RPIC increased the volume of information calls dramatically. Initial trend analysis indicated that the availability of toll-free access has reversed the erosion of exposure-related calls. | pubmed_156_4283 |
pubmed_687_5580 | During neural network development, growing axons read a map of guidance cues expressed in the surrounding tissue that lead the axons toward their targets. In particular, Xenopus retinal ganglion axons use the cues Slit1 and Semaphorin 3a (Sema3a) at a key guidance decision point in the mid-diencephalon in order to continue on to their midbrain target, the optic tectum. The mechanisms that control the expression of these cues, however, are poorly understood. Extrinsic Fibroblast Growth Factor (Fgf) signals are known to help coordinate the development of the brain by regulating gene expression. Here, we propose Lhx2/9 and Etv1 as potential downstream effectors of Fgf signalling to regulate slit1 and sema3a expression in the Xenopus forebrain. We find that lhx2/9 and etv1 mRNAs are expressed complementary to and within slit1/sema3a expression domains, respectively. Our data indicate that Lhx2 functions as an indirect repressor in that lhx2 overexpression within the forebrain downregulates the mRNA expression of both guidance genes, and in vitro lhx2/9 overexpression decreases the activity of slit1 and sema3a promoters. The Lhx2-VP16 constitutive activator fusion reduces sema3a promoter function, and the Lhx2-En constitutive repressor fusion increases slit1 induction. In contrast, etv1 gain of function transactivates both guidance genes in vitro and in the forebrain. Based on these data, together with our previous work, we hypothesize that Fgf signalling promotes both slit1 and sema3a expression in the forebrain through Etv1, while using Lhx2/9 to limit the extent of expression, thereby establishing the proper boundaries of guidance cue expression. | 10.1016/j.neuroscience.2020.03.021 |
pubmed_729_20059 | Although epilepsy affects men and women equally, there are many women's health issues in epilepsy, especially for women of childbearing age. These issues, which include menstrual cycle influences on seizure activity (catamenial epilepsy), interactions of contraceptives with antiepileptic drugs (AEDs), pharmacokinetic changes during pregnancy, teratogenicity and the safety of breastfeeding, challenge both the woman with epilepsy and the many healthcare providers involved in her care. Although the information in the literature on women's issues in epilepsy has grown steeply in recent years, there are many examples showing that much work is yet to be done. The purpose of this article is to review these issues and describe practical considerations for women of childbearing age with epilepsy. The article addresses the established or "first-generation" AEDs (phenobarbital, phenytoin, primidone, carbamazepine, ethosuximide and valproic acid) and the "second-generation" AEDs (felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, vigabatrin and zonisamide). Although a relationship between hormones and seizure activity is present in many women, good treatment options for catamenial epilepsy remain elusive. Drug interactions between enzyme-inducing AEDs and contraceptives are well documented. Higher dosages of oral contraceptives or a second contraceptive method are suggested if women use an enzyme-inducing AED. Planned pregnancy and counselling before conception is crucial. This counselling should include, but is not limited to, folic acid supplementation, medication adherence, the risk of teratogenicity and the importance of prenatal care. AED dosage adjustments may be necessary during pregnancy and should be based on clinical symptoms, not entirely on serum drug concentrations. Many groups have turned their attention to women's issues in epilepsy and have developed clinical practice guidelines. Although the future holds promise in this area, many questions and the need for progress remain. | 10.2165/00003088-200241080-00002 |
pubmed_310_2503 | Promyelocytic leukemia (PML) is the organizer of nuclear matrix domains, PML nuclear bodies (NBs), with a proposed role in apoptosis control. In acute promyelocytic leukemia, PML/retinoic acid receptor (RAR) alpha expression disrupts NBs, but therapies such as retinoic acid or arsenic trioxide (As2O3) restore them. PML is conjugated by the ubiquitin-related peptide SUMO-1, a process enhanced by As2O3 and proposed to target PML to the nuclear matrix. We demonstrate that As2O3 triggers the proteasome-dependent degradation of PML and PML/RARalpha and that this process requires a specific sumolation site in PML, K160. PML sumolation is dispensable for its As2O3-induced matrix targeting and formation of primary nuclear aggregates, but is required for the formation of secondary shell-like NBs. Interestingly, only these mature NBs harbor 11S proteasome components, which are further recruited upon As2O3 exposure. Proteasome recruitment by sumolated PML only likely accounts for the failure of PML-K160R to be degraded. Therefore, studying the basis of As2O3-induced PML/RARalpha degradation we show that PML sumolation directly or indirectly promotes its catabolism, suggesting that mature NBs could be sites of intranuclear proteolysis and opening new insights into NB alterations found in viral infections or transformation. | 10.1084/jem.193.12.1361 |
pubmed_336_5666 | PURPOSE
Peripheral neuropathy (PN) is an identified risk of systemic antibacterial therapy with fluoroquinolones. The risk and its severity, including the development of Guillain-Barré syndrome (GBS) between individual agents is uncertain. This study examines the association between fluoroquinolones and PN and GBS in cases spontaneously reported to the FDA Adverse Event Reporting System.
METHODS
Cases reported to FDA Adverse Event Reporting System between 1997 and 2012 were retrieved. The Medical Dictionary for Regulatory Activities Preferred Term was used to define PN and GBS. Individual fluoroquinolones were identified by generic names and route of administration. Empirical Bayes Geometric Mean (EBGM) with 95% confidence interval (EB05-EB95) was calculated as disproportionality measure. Safety signals with EB05 2 or more was considered a significant disproportional increase in the event reporting of at least twice times higher than that expected.
RESULTS
There were 539 PN reports out of 46,257 adverse event reports submitted for fluoroquinolones. Nine percent of PN reports were for GBS. Significant disproportionality of PN (EBGM 2.70; EB05-EB95 2.51-2.90) and GBS (EBGM 3.22; EB05-EB95 2.55-4.02) was identified for fluoroquinolones. Signals of PN were detected for ciprofloxacin (EBGM 3.24; EB05-EB95 2.87-3.66) and levofloxacin (EBGM 3.36; EB05-EB95 3.02-3.72). A GBS signal was detected for ciprofloxacin (EBGM 4.15; EB05-EB95 2.94-5.74). GBS and PN, respectively, ranked 6th and 8th among reported neurologic events.
CONCLUSIONS
This study re-emphasizes the link between fluoroquinolones and PN and shows the potential association with more severe forms of nerve damage, for example, GBS. Unless the benefit of fluoroquinolone therapy (e.g., overwhelming infection or development of bacterial resistance) outweighs PN risk, treatment with alternative antibacterial agents is recommended. | pubmed_336_5666 |
pubmed_381_22529 | Defective reactive oxygen species (ROS) production by genetically determined variants of the NADPH oxidase 2 (NOX2) complex component, NCF4, leads to enhanced production of autoantibodies to collagen type II (COL2) and severe collagen-induced arthritis (CIA) in mice. To further understand this process, we used mice harboring a mutation in the lipid endosomal membrane binding site (R58A) of NCF4 subunit. This mutation did not affect the extracellular ROS responses but showed instead decreased intracellular responses following B cell stimulation. Immunization with COL2 led to severe arthritis with increased antibody levels in Ncf458A mutated animals without significant effects on antigen presentation, autoreactive T cell activation and germinal center formation. Instead, plasma cell formation was enhanced and had altered CXCR3/CXCR4 expression. This B cell intrinsic effect was further confirmed with chimeric B cell transfer experiments and in vitro LPS or CD40L with anti-IgM stimulation. We conclude that NCF4 regulates the terminal differentiation of B cells to plasma cells through intracellular ROS. | 10.1016/j.redox.2022.102422 |
pubmed_1041_9020 | The phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) network plays a key regulatory function in cell survival, proliferation, migration, metabolism, angiogenesis, and apoptosis. Genetic aberrations found at different levels, either with activation of oncogenes or inactivation of tumor suppressors, make this pathway one of the most commonly disrupted in human breast cancer. The PI3K-dependent phosphorylation and activation of the serine/threonine kinase AKT is a key activator of cell survival mechanisms. The activation of the oncogene PIK3CA and the loss of regulators of AKT including the tumor suppressor gene PTEN are mutations commonly found in breast tumors. AKT relieves the negative regulation of mTOR to activate protein synthesis and cell proliferation through S6K and 4EBP1. The common activation of the PI3K pathway in breast cancer has led to the development of compounds targeting the effector mechanisms of the pathway including selective and pan-PI3K/pan-AKT inhibitors, rapamycin analogs for mTOR inhibition, and TOR-catalytic subunit inhibitors. The influences of other oncogenic pathways such as Ras-Raf-Mek on the PI3K pathway and the known feedback mechanisms of activation have prompted the use of compounds with broader effect at multiple levels and rational combination strategies to obtain a more potent antitumor activity and possibly a meaningful clinical effect. Here, we review the biology of the network, its role in the development and progression of breast cancer, and the evaluation of targeted therapies in clinical trials. | 10.1634/theoncologist.2010-0402 |
pubmed_529_4353 | BACKGROUND
Patients' satisfaction is an indicator of the quality of healthcare services. Its measurement involves developing and validating complex instruments. The purpose of this study was to validate a scale for measuring hemodialysis patients' satisfaction with the provided care, the Scale for Evaluation of Hemodialysis Patient's Satisfaction with Service provided at a Chronic Kidney Disease Unit (or ESUR-HD, its acronym in Spanish).
METHODS
The instrument was applied to 370 patients undergoing hemodialysis for undertaking exploratory and confirmatory analyses, internal consistency assessment, and Rasch analysis. In order to assure test-retest reliability, the instrument was applied once again to 54 patients after 2 days. Convergent validity was assessed by estimating correlation coefficients based on the results of 2 instruments (ESUR-HD and SDIALOR) simultaneously applied in 70 patients. Sensitivity to change was assessed in 40 patients by comparing the scale scores before and after an intervention consisting of improved care conditions.
RESULTS
In the 44 items of the scale a 9-factor structure was found (1: Facilities and organization of the service. 2: Care provided by the attending nurses and/or nursing assistants. 3: Attention to psychological and administrative issues. 4: Contact and social work personnel. 5: Medical attention and care. 6: Nutritional attention and care. 7: Medications supply and quality. 8: Features of the admission process. 9: Attention and care provided by head nurses). Chronbach alpha for the scale was 0.96. Lin's concordance correlation for the whole scale was 0.85. Although statistically different from 0, low correlation values with dimensions from another scale measuring the same attribute were found. The scale could detect construct changes through increased scores in specific dimensions following an intervention aimed at enhancing satisfaction. Rasch analysis located improperly fit items and suggested reducing items measurement levels. Despite the effect encountered, Rasch analysis showed the scale might not capture variability in upper attribute levels.
CONCLUSION
The ESUR-HD scale measures hemodialysis patients' satisfaction in one dimension with 9 domains. Validity and reliability are adequate. The instrument may detect changes in the construct. Subsequent versions of the scale should include new items allowing improved discrimination amongst high satisfaction levels.
TRIAL REGISTRATION
ISRCTN45318400 . April 05, 2017. | 10.1186/s12913-017-2251-y |
pubmed_973_22759 | This study evaluated a mail and telephone intervention to improve breast health behaviors while maintaining quality of life. Women recruited from the general public were randomized to a stepped-intensity intervention consisting of mailings, telephone calls, and counseling (if requested or appropriate given a woman's genetic risk for breast cancer) or to a delayed treatment control group. Outcomes (mammography screening and quality of life) were measured at baseline in a telephone survey and again at a 12-month follow-up period. Women in the intervention group significantly increased screening mammography uptake by 12% and quality of life by 5.3 scale points compared to control participants. Changes in knowledge of breast cancer, genetic testing, and cancer worry all significantly predicted intervention changes. This successful intervention can help women make better breast health choices without causing increased worry. | 10.1177/1090198109348463 |
pubmed_584_16357 | Ciliates are a group of microbial eukaryotes defined by the presence of dimorphic nuclei-each cell contains both a transcriptionally active macronucleus and a germline micronucleus. During the development of the macronucleus, germline chromosomes are rearranged through extensive fragmentation, removal of internally excised sequences (IESs) and DNA amplification. We have characterized three IESs in the gene that encodes alpha-tubulin in the phyllopharyngean ciliate Chilodonella uncinata. The IESs are located within the coding domain, range in size from 81 to 107 bp, and are flanked by direct repeats that vary in length from 6 to 8 bp. All three IESs are moderately AT-rich and each contains two copies of a conserved sequence motif. These data provide evidence for the existence of IESs in phyllopharyngean ciliates and suggest that IES processing in C. uncinata may rely on a novel cis-acting sequence. Comparisons of the IESs in C. uncinata with those of 'model' ciliates-Paramecium, Tetrahymena, Euplotes, Oxytricha and Stylonychia-reveal considerable variation in chromosomal processing among ciliates. | 10.1016/j.gene.2003.08.003 |
pubmed_416_2955 | Globular proteins fold by minimizing the nonpolar surface that is exposed to water, while simultaneously providing hydrogen-bonding interactions for buried backbone groups, usually in the form of secondary structures such as alpha-helices, beta-sheets, and tight turns. A primary thermodynamic driving force for the formation of globular structure is thus the sequestration of nonpolar groups, but the correlation between the parts of proteins that are observed to fold first (termed folding initiation sites) and the "hydrophobicity" (as customarily defined) of the amino acids in these regions has been quite weak. It has previously been noted that many amino acid side chains contain considerable nonpolar sections, even if they also contain polar or charged groups. For example, a lysine side chain contains four methylenes, which may undergo hydrophobic interactions if the charged epsilon-NH(3)(+) group is salt-bridged or hydrogen-bonded. Folding initiation sites might therefore contain not only accepted "hydrophobic" amino acids, but also larger charged side chains. Recent experiments on the folding of mutant apomyoglobins provides corroboration for models based on the hypothesis that folding initiation sites arise from hydrophobic interactions. A near-perfect correlation was observed between the areas of the molecule that are present in the burst-phase kinetic intermediate and both the free energy of formation of hydrophobic initiation sites and the parameter "average area buried upon folding," which pinpoints large side chains, even those containing charged or polar portions. These results provide a putative mechanism for the control of protein-folding initiation and growth by polar/nonpolar sequence propensity alone. | 10.1073/pnas.0605504103 |
pubmed_624_13561 | The structure, historical development and major research problems confronting veterinary parasitology in the U.S.A. are reviewed 100 years after the cooperative federal-state experiment station system was authorized through passage of the Hatch Act by the U.S. Congress in 1887. The story of Texas cattle fever eradication from the American south exemplifies historical and functional aspects of the experiment station system. The distribution and importance of parasite problems of livestock, companion animals and parasitic zoonoses are summarized in the context of larger national agricultural issues. | 10.1016/0304-4017(89)90090-3 |
pubmed_415_4413 | Joint stiffness and stability are reliant on coordinated muscle activity which may differ depending on initial posture and loading during sudden perturbations. This study investigated the effects of arm posture and hand load on muscle activity during perturbations of the arm. Fifteen male participants experienced perturbations to the wrist causing elbow extension using a combination of three body postures (standing, supine, sitting) and three hand load conditions (no, solid, and fluid loads), with known and unknown timing. Surface EMG was collected from eight muscles of the right upper extremity. The response to sudden loading was examined using muscle activities pre (baseline) and post (reflex) perturbation. During the baseline period, known perturbation timing resulted in greater muscular activity than for unknown timing, while the opposite was found for the reflex period. During the reflex period with fluid load, biceps brachii and brachioradialis demonstrated increased activity of 2.4% and 4.0% of maximum respectively, from supine to standing. During the reflex period, the fluid load resulted in forearm co-contraction 23% and 47% greater than the solid and no load conditions. Body orientation and hand loading influenced muscular response to elbow perturbations. Muscle co-contraction at the elbow during known timing suggests a contribution to elbow joint stability that may reduce injury risk caused by sudden elbow loading. | 10.1016/j.jelekin.2011.11.006 |
pubmed_936_13488 | Rabies virus has existed for thousands of years and is circulating in many species. In the present study, a total of 2896 rabies viruses isolated worldwide were phylogenetically classified into ten clusters based on the G gene sequence, and these clusters showed a close relationship with the hosts and regions that they were isolated from. Eighty-three representative G sequences were selected from ten clusters and were used to construct pseudoviruses using the VSV vector. The phylogenetic relationships, infectivity and antigenicity of the representative 83 pseudotyped rabies viruses were comprehensively analyzed. Eighty three pseudoviruses were divided into four antigentic clusters (GAgV), of which GAgV4 showed poor neutralization to all immunized sera. Further analysis showed that almost all strains in the GAgV4 were isolated from wild animals in the America, especially bats and skunks. No significant relationship in terms of phylogeny, infectivity and antigenicity was proved. Amino acid mutations at residues 231and 436 can affect the infectivity, while mutations at residues 113, 164 and 254 may affect the sensitivity to immunized animal sera, especially residue 254. We recommend close monitoring of infectivity and antigenicity, which should be more precise than simple genetic analysis. | 10.1080/22221751.2022.2078742 |
pubmed_852_3493 | BACKGROUND
Premotor cortical regions (PMC) play an important role in the orchestration of motor function, yet their role in compensatory mechanisms in a disturbed motor system is largely unclear. Previous studies are consistent in describing pronounced anatomical and functional connectivity between the PMC and the primary motor cortex (M1). Lesion studies consistently show compensatory adaptive changes in PMC neural activity following an M1 lesion. Non-invasive brain modification of PMC neural activity has shown compensatory neurophysiological aftereffects in M1. These studies have contributed to our understanding of how M1 responds to changes in PMC neural activity. Yet, the way in which the PMC responds to artificial inhibition of M1 neural activity is unclear. Here we investigate the neurophysiological consequences in the PMC and the behavioral consequences for motor performance of stimulation mediated M1 inhibition by cathodal transcranial direct current stimulation (tDCS).
PURPOSE
The primary goal was to determine how electrophysiological measures of PMC excitability change in order to compensate for inhibited M1 neural excitability and attenuated motor performance.
HYPOTHESIS
Cathodal inhibition of M1 excitability leads to a compensatory increase of ipsilateral PMC excitability.
METHODS
We enrolled 16 healthy participants in this randomized, double-blind, sham-controlled, crossover design study. All participants underwent navigated transcranial magnetic stimulation (nTMS) to identify PMC and M1 corticospinal projections as well as to evaluate electrophysiological measures of cortical, intracortical and interhemispheric excitability. Cortical M1 excitability was inhibited using cathodal tDCS. Finger-tapping speeds were used to examine motor function.
RESULTS
Cathodal tDCS successfully reduced M1 excitability and motor performance speed. PMC excitability was increased for longer and was the only significant predictor of motor performance.
CONCLUSION
The PMC compensates for attenuated M1 excitability and contributes to motor performance maintenance. | 10.1371/journal.pone.0057425 |
pubmed_641_6100 | Residues in beta-sheets occur in two distinct tertiary contexts: central strands, bordered on both sides by other beta-strands, and edge strands, bordered on only a single side by another beta-strand. The delta delta G values for beta-sheet formation measured at an edge beta-strand of the IgG-binding domain of protein G(GB1) are quite different from those obtained previously at a central position in the same protein. In particular, there is no correlation at the edge position with statistically determined beta-sheet-forming preferences. The differences between beta-sheet propensities measured at central and edge beta-strands, delta delta delta G values, correlate with the values of water/octanol transfer free energies and side-chain non-polar surface area for the amino acids. These results strongly suggest that, unlike alpha-helix formation, beta-sheet formation is determined in large part by tertiary context, even at solvent-accessible sites, and not by intrinsic secondary structure preferences. | 10.1038/371264a0 |
pubmed_1058_20924 | The purpose of the questionnaire survey was to gather data on dental health knowledge from 12 year-old school children and 15-19 year-old adolescents including self-reported dental behaviours and factors affecting regular dental attendance. The completed questionnaires of 350 children and 345 adolescents were analysed. The majority of young people were able to correctly identify the functions of teeth and cariogenic foods, and were also aware of the signs of periodontal disease. However, they incorrectly defined the meaning of dental caries and dental plaque. Also students claimed good oral hygiene behaviour and willingness to receive necessary treatment for a carious tooth from a dentist. Sixty five per cent of children and 74 per cent of adolescents, went to a dentist at some time and were likely to receive extraction at their last visit. Cost and fear were found to be the common barriers for regular dental attendance. | 10.1002/j.1875-595x.1997.tb00782.x |
pubmed_591_10066 | Health topics are omnipresent in the media. However, although both informational and entertainment formats can increase public understanding of health and illness, media representations of diseases involve challenges as well as opportunities. The entertainment-education (E-E) approach highlights the positive effects of incorporating health messages into entertainment media. The goal of influencing awareness, knowledge and attitudes is reached by transporting the audience into a narrative, which as such enhances persuasive effects and suppresses counterarguing. The NBC sitcom The Michael J. Fox Show (TMJFS) is an E-E format inspired by the actor's own experiences with Parkinson's disease (PD). Using TMJFS as an exemplar, we conducted a multimethodological study to understand both the challenges and the opportunities of E-E comedy formats. A content analysis focusing on the representation of PD in TMJFS showed a focus on motoric symptoms of PD. Subsequent recap analyses and qualitative interviews were conducted to better understand different readings of the show in terms of its informative and entertaining aspects. Additionally, we performed a standardized online survey and an experiment to measure attitudinal effects of TMJFS. | 10.1558/cam.28981 |
pubmed_725_7901 | Erythropoietin (Epo) is an unambiguous inducer of red cell differentiation in mammals. Purified Epo, derived from urine of anemic patients, is a glycoprotein of molecular weight about 34,000. There are two forms with the same biological activity and amino acid composition but with differing carbohydrate compositions. All of the carbohydrate is in the form of N-linked complex oligosaccharides. Erythropoietin appears to contain three domains, two protease-resistant regions containing all of the carbohydrate, connected by a protease-sensitive region containing the active site. Cells derived from mice infected with the anemia variant of the Friend leukemia, bind Epo specifically. The receptors have a dissociation constant of about 5 nM and there are only 600-700 per cell. Erythropoietin has a rapid effect on the transcription and processing of the globin genes. Among the enzymes of heme synthesis, it has an early effect only on uroporphyrinogen synthase. Studies with Epo and colony-stimulating factor (CSF) suggest that these inducers compete for the same, or very closely related cells of the hemopoietic system. When marrow cells are put into close apposition by centrifugation, their responses to Epo and CSF and the competitive actions of these inducers increase. | pubmed_725_7901 |
pubmed_857_5287 | The staff and services of the endocrine biochemistry laboratory are essential to the efficient investigation of infertility. Each centre should adopt a detailed strategy for the investigation of the infertile couple which specifies the hormone analyses required at each stage. Appropriate first-line hormone tests should be selected after a thorough clinical history and physical examination of both partners. Second-line hormone testing should be determined from the results of the initial investigation and should be restricted to requests that either confirm or clarify an endocrine basis to infertility or monitor the response to treatment. The clinical biochemist should advise on specimen timing and collection, have responsibility for guaranteeing time and valid hormone results, and be part of the team that audits the overall strategy and the outcome for individual patients. | 10.1136/jcp.46.9.790 |
pubmed_417_13350 | Although the efficacy of hormonal replacement therapy (HRT) regarding numerous consequences of menopause is proven, its prevalence of use is low, as is compliance with the prescribed treatment. The aim of this work was to study the factors influencing a woman's decision to take HRT by analyzing the determinants of HRT use of at least 6 months' duration among post-menopausal women working for a French company and enrolled in a cohort study. Special attention was paid to the women's expectations of HRT. We compared two groups of women: 113 current HRT users who had been users for at least 6 months and 101 never users. Among the 113 current users, the most frequent treatment was a combination of oestrogen and progestin (86%). The determinants of HRT use for at least 6 months included a prior spinal radiograph, which showed a significant relationship with the use of hormone treatment (odds ratio (OR) 2.4; 95% confidence interval (CI) 1.2-4.7), a current marriage (OR 2.5; 95% CI 1.3-5.1) and previous hot flushes (OR 2.4; 95% CI 1.2-4.9). The strongest determinant was an expectation that HRT would prevent osteoporosis (OR 5.0; 95% CI 2.2-11.6). In this population concern about osteoporosis appears to be an important determinant of HRT use. Our results underline the importance of the diffusion of information among physicians and women about HRT's benefits, especially its efficacy in preventing osteoporosis. | 10.1007/BF02352256 |
pubmed_977_19790 | A Gram-stain-negative, aerobic, flagellated and rod-shaped bacterium, designated strain SM2107T, was isolated from a deep-sea sediment sample collected from the Southwest Indian Ocean. Strain SM2107T grew at 4-40 °C and with 0-10.0 % (w/v) NaCl. It reduced nitrate to nitrite and hydrolysed casein, gelatin, chitin and DNA. The phylogenetic trees based on the 16S rRNA genes and single-copy orthologous clusters showed that strain SM2107T, together with Rheinheimera tuosuensis, Rheinheimera perlucida and Arsukibacterium ikkense, formed a separate clade, having the highest similarity to the type strain of Rheinheimera tuosuensis (98.3%). The major polar lipids were phosphatidylethanolamine and phosphatidylglycerol and the major cellular fatty acids were summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c), C16 : 0, C17 : 1 ω8с and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c). The only respiratory quinone was Q-8. The genomic DNA G+C content of strain SM2107T was 48.8 %. The digital DNA-DNA hybridization values between strain SM2107T and type strains of Rheinheimera tuosuensis, Rheinheimera perlucida and Arsukibacterium ikkense were 41.16, 37.70 and 31.80 %, while the average amino acid identity values between them were 87.59, 86.76 and 83.64 %, respectively. Based on the polyphasic evidence presented in this study, strain SM2107T was considered to represent a novel species within the genus Arsukibacterium, for which the name Arsukibacterium indicum was proposed. The type strain is SM2107T (=MCCC M24986T=KCTC 82921T). Moreover, the transfer of Rheinheimera tuosuensis and Rheinheimera perlucida to the genus Arsukibacterium as Arsukibacterium tuosuense comb. nov. (type strain TS-T4T=CGMCC 1.12461T=JCM 19264T) and Arsukibacterium perlucidum comb. nov. (type strain BA131T=LMG 23581T=CIP 109200T) is also proposed. | 10.1099/ijsem.0.005455 |
pubmed_95_15094 | To understand the interspike interval (ISI) variability displayed by visual cortical neurons (Softky & Koch, 1993), it is critical to examine the dynamics of their neuronal integration, as well as the variability in their synaptic input current. Most previous models have focused on the latter factor. We match a simple integrate-and-fire model to the experimentally measured integrative properties of cortical regular spiking cells (McCormick, Connors, Lighthall, & Prince, 1985). After setting RC parameters, the post-spike voltage reset is set to match experimental measurements of neuronal gain (obtained from in vitro plots of firing frequency versus injected current). Examination of the resulting model leads to an intuitive picture of neuronal integration that unifies the seemingly contradictory 1/square root of N and random walk pictures that have previously been proposed. When ISIs are dominated by postspike recovery, 1/square root of N arguments hold and spiking is regular; after the "memory" of the last spike becomes negligible, spike threshold crossing is caused by input variance around a steady state and spiking is Poisson. In integrate-and-fire neurons matched to cortical cell physiology, steady-state behavior is predominant, and ISIs are highly variable at all physiological firing rates and for a wide range of inhibitory and excitatory inputs. | 10.1162/neco.1997.9.5.971 |
pubmed_731_4392 | Community participation is commonly regarded as pivotal in enabling the success of many health initiatives. However, the theoretical constructs, and evidence about the contextual drivers and relational issues that shape participation is lacking. The aim of this systematic review was to examine the evidence for published academic literature on community participation in relation to general, non-disease specific health initiatives, including the use of theories to inform community participation, and the study of contextual drivers and relational issues that influence community participation, with a focus on high and upper-middle income countries. We searched multiple databases including Medline, Embase, Scopus, LILACs and Global Health from January 2000 to September 2016. We screened papers for inclusion, then conducted data extraction and a narrative synthesis of the data. Only papers that focused on general health were included. Disease-specific literature was excluded. 27,232 records were identified, with 23,468 after duplicate removal. 79 papers met our final inclusion criteria. Overall, our findings show that strategies to encourage community participation in health initiatives can be categorized along a continuum that varies from less to more participation and control among the community. Our analysis of reported outcomes demonstrates that community participation in general health initiatives can contribute to positive process, social and health outcomes. Social outcomes are more often associated with increasing community participation in our selection of papers. Overall, our findings reaffirm the understanding that community participation is a complex process that is strongly influenced by the context in which it occurs, and that social factors such as power relations must be carefully considered. There is a need for more robustly designed studies to improve the theorization of community participation, and to draw out a better understanding of how tangible and intangible elements such as power, influence community participation and its outcomes. | 10.1016/j.socscimed.2018.07.019 |
pubmed_391_16523 | Needle-aspiration cytology of a case of benign neurilemoma (Schwannoma) from the neck is presented. It was clinically diagnosed as an enlarged lymph node, while on aspiration cytology, it was diagnosed as a pleomorphic adenoma. An excision biopsy, however, was diagnostic of neurilemoma. A review of cytologic material was undertaken, and it was felt that the cytologic features in Papanicolaou stained preparations in the aspirate were present that initially should have enabled the correct cytodiagnosis and distinction from a pleomorphic adenoma. The findings presented in this study were considered to be an example of a potential pitfall in the aspiration cytodiagnosis of a neurilemoma. | 10.1002/dc.2840070615 |
pubmed_707_22303 | In recent years, postmortem biochemistry analysis has gradually been applied to forensic practice, providing objective evidence for health conditions before death, disease pathophysiological processes and forensic diagnosis of postmortem interval and cause of death. It is of great significance to understand the change patterns of postmortem biochemical indicators and their applications in forensic medicine. This article reviews the research progress of postmortem biochemistry and its application in forensic medicine, it summarizes the existing problems of postmortem biochemistry analysis in forensic medicine of China and discusses the application prospect of postmortem biochemistry analysis in forensic medicine. This review is expected to provide references for forensic practitioners. | 10.12116/j.issn.1004-5619.2020.401205 |
pubmed_765_23716 | Cytochrome P450 monooxygenases (CYPs/P450s) are well known for their role in organisms' primary and secondary metabolism. Among 20 P450s of the tuberculosis-causing Mycobacterium tuberculosis H37Rv, CYP128A1 is particularly important owing to its involvement in synthesizing electron transport molecules such as menaquinone-9 (MK9). This study employs different in silico approaches to understand CYP128 P450 family's distribution and structural aspects. Genome data-mining of 4250 mycobacterial species has revealed the presence of 2674 CYP128 P450s in 2646 mycobacterial species belonging to six different categories. Contrast features were observed in the CYP128 gene distribution, subfamily patterns, and characteristics of the secondary metabolite biosynthetic gene cluster (BGCs) between M. tuberculosis complex (MTBC) and other mycobacterial category species. In all MTBC species (except one) CYP128 P450s belong to subfamily A, whereas subfamily B is predominant in another four mycobacterial category species. Of CYP128 P450s, 78% was a part of BGCs with CYP124A1, or together with CYP124A1 and CYP121A1. The CYP128 family ranked fifth in the conservation ranking. Unique amino acid patterns are present at the EXXR and CXG motifs. Molecular dynamic simulation studies indicate that the CYP128A1 bind to MK9 with the highest affinity compared to the azole drugs analyzed. This study provides comprehensive comparative analysis and structural insights of CYP128A1 in M. tuberculosis. | 10.3390/ijms21144816 |
pubmed_1112_2590 | BACKGROUND
Allergic lung inflammation is mediated by allergen-specific T responses, which are negatively regulated by regulatory T cells (Tregs). Previous studies have reported that inoculation of indigenous Clostridium species in the early lives of mice can induce Tregs that colonize the colon. However, whether inoculation of C leptum alone in adult mice could induce systemic Treg responses and inhibit allergic airway inflammation remains unclear.
OBJECTIVE
To investigate the effect of oral administration of C leptum on systemic Treg responses and allergic airway inflammation in a mouse model of asthma.
METHODS
Adult BABL/c mice were injected with ovalbumin to induce asthma and treated orally with C leptum or vehicle daily for 2 weeks. The numbers of Foxp3(+)CD4(+)CD25(+) Tregs in both the spleen and mediastinal lymph nodes were examined by flow cytometry. After allergen challenge, the airway hyperresponsiveness of individual mice was measured, and the numbers of inflammatory infiltrates and the levels of cytokines in bronchoalveolar lavage fluids ere determined.
RESULTS
Oral feeding with C leptum increased the percentage and total number of Tregs in the spleens and mediastinal lymph nodes at 14 days after inoculation and attenuated allergen-induced airway hyperresponsiveness and inflammation by inhibiting inflammatory cytokine production but enhancing interleukin 10 and transforming growth factor β1 production in the lungs.
CONCLUSION
Oral treatment with C leptum can attenuate induced allergic airway inflammation in adult mice. | 10.1016/j.anai.2012.06.017 |
pubmed_290_2243 | Directional modulation (DM) technique has the ability to enhance the physical layer security (PLS) of wireless communications. Conventional DM schemes are usually based on a single antenna array with the basic assumption that eavesdroppers (Eves) and legitimate users (LUs) are in different directions. However, it is possible that Eves are in the same direction as LUs in practical applications. As a result, signals received by Eves will be approximately the same or even in better quality than those received by LUs. To address the neighbor security issue, we introduce a multiple antenna arrays model at the transmitter side with the help of the artificial noise (AN)-aided DM technique to achieve secure and precise DM transmission in this paper. Meanwhile, to recover the mixed useful signals, two novel DM schemes based on single- and multi-carrier multiple antenna arrays model are proposed, respectively. In addition, the symbol error rate (SER), secrecy rate, and robustness performance of the proposed DM schemes were analyzed and simulated. Simulations validate the effectiveness of the proposed DM schemes and demonstrate that multiple antenna arrays model based DM methods outperform single antenna array model aided DM methods in security. | 10.3390/s19224833 |
pubmed_1109_500 | Rutherford and McIntosh (J Autism Dev Disord 37:187–196, 2007) demonstrated that individuals with autism spectrum disorder (ASD) are more tolerant than controls of exaggerated schematic facial expressions, suggesting that they may use an alternative strategy when processing emotional expressions. The current study was designed to test this finding using photographs of real people. In addition, two control tasks were added to eliminate alternative explanations. We replicated the findings of Rutherford and McIntosh (J Autism Dev Disord 37:187–196, 2007) and also demonstrated that adults with ASD do not show this tolerance when evaluating how realistic the expressions are. These results suggest adults with ASD employ a rule-based strategy to a greater extent than typical adults when processing facial expressions but not when processing other aspects of faces. | 10.1007/s10803-013-1953-1 |
pubmed_403_6812 | As many other conferences held in 2020, the 17th Drug Information Association (DIA) Japan Annual Meeting 2020 was held virtually for the first time due to the COVID-19 crisis. The virtual platform delivered 64 sessions across 3 days and allowed participants to join the sessions flexibly, interactively participate in Q and A and connect with fellows without boundaries. The opening speech was addressed by Hajime Saijo (DIA Japan) to introduce the conference theme "Beyond Innovation" and key sessions featured discussions on future healthcare, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) 30-year anniversary, the Pharmaceuticals and Medical Devices Agency (PMDA) town hall, patient-focused drug development and global drug development. This meeting report covers the topics discussed from the programs featuring patient engagement, innovative drug development and new technologies. | 10.1358/dot.2020.56.12.3255085 |
pubmed_922_23475 | The brain requires diverse segregated and integrated processing to perform normal functions in terms of anatomical structure and self-organized dynamics with critical features, but the fundamental relationships between the complex structural connectome, critical state, and functional diversity remain unknown. Herein, we extend the eigenmode analysis to investigate the joint contribution of hierarchical modular structural organization and critical state to brain functional diversity. We show that the structural modes inherent to the hierarchical modular structural connectome allow a nested functional segregation and integration across multiple spatiotemporal scales. The real brain hierarchical modular organization provides large structural capacity for diverse functional interactions, which are generated by sequentially activating and recruiting the hierarchical connectome modes, and the critical state can best explore the capacity to maximize the functional diversity. Our results reveal structural and dynamical mechanisms that jointly support a balanced segregated and integrated brain processing with diverse functional interactions, and they also shed light on dysfunctional segregation and integration in neurodegenerative diseases and neuropsychiatric disorders. | 10.1103/PhysRevLett.123.038301 |
pubmed_1077_14041 | Given the popularity of social media among young men who have sex with men (YMSM), and in light of YMSM's elevated and increasing HIV rates, we tested the feasibility, acceptability and preliminary efficacy of a live chat intervention delivered on Facebook in reducing condomless anal sex and substance use within a group of high risk YMSM in a pre-post design with no control group. Participants (N = 41; 18-29 years old) completed up to eight one-hour motivational interviewing and cognitive behavioral skills-based online live chat intervention sessions, and reported on demographic, psychosocial, and behavioral characteristics at baseline and immediately post-intervention. Analyses indicated that participation in the intervention (n = 31) was associated with reductions of days of drug and alcohol use in the past month and instances of anal sex without a condom (including under the influence of substances), as well as increases in knowledge of HIV-related risks at 3-month follow-up. This pilot study argues for the potential of this social media-delivered intervention to reduce HIV risk among a most vulnerable group in the United States, in a manner that was highly acceptable to receive and feasible to execute. A future randomized controlled trial could generate an intervention blueprint for providers to support YMSM's wellbeing by reaching them regardless of their geographical location, at a low cost. | 10.1007/s10461-014-0911-z |
pubmed_705_6619 | BACKGROUND
Cardiac involvement is common in acute Lyme disease, and case reports suggest that cardiac abnormalities might also occur years after the primary infection.
OBJECTIVE
To determine the prevalence of cardiac abnormalities in persons with previously treated Lyme disease.
DESIGN
Population-based, retrospective cohort study with controls.
SETTING
Nantucket Island, Massachusetts.
PARTICIPANTS
From among 3703 adult respondents to a total-population (n = 6046) mail survey, 336 (176 case-patients and 160 controls) were randomly selected for clinical evaluation.
MEASUREMENTS
Current cardiac symptoms and major or minor abnormal electrocardiographic features, including heart rate; rhythm; axis; PR, QRS, and QT intervals; QRS structure; atrioventricular blocks; and ST-segment and T-wave changes.
RESULTS
Persons with Lyme disease (case-patients, n = 176) (mean duration from disease onset to study evaluation, 5.2 years) and persons without evidence of previous Lyme disease (controls, n = 160) did not differ significantly in their patterns of current cardiac symptoms and electrocardiographic findings, including heart rate (P > 0.2), PR interval (P = 0.15), QRS interval (P > 0.2), QT interval (P > 0.2), axis (P > 0.2), presence of arrhythmias (P > 0.2), first-degree heart block (P = 0.12), bundle-branch block (P > 0.2), and ST-segment abnormalities (P > 0.2). In multivariate analyses that adjusted for age, sex, and previous heart disease, a history of previously treated Lyme disease was not associated with either major (odds ratio, 0.78; P > 0.2) or minor (odds ratio, 1.09; P > 0.2) electrocardiographic abnormalities.
CONCLUSION
Persons with a history of previously treated Lyme disease do not have a higher prevalence of cardiac abnormalities than persons without a history of Lyme disease. | 10.7326/0003-4819-128-5-199803010-00002 |
pubmed_6_21615 | The burden of gastrointestinal (GI) cancer is increasing worldwide, and in the past decade, cancer had entered the list of chronic debilitating diseases whose risk is substantially increased by hypernutrition. Obesity may increase the risk of cancer by the imbalance of various mechanisms including insulin and insulin-like growth factor1 (IGF-I) signaling, systemic inflammation, immune dysregulation, tumor angiogenesis, adipokines secretion, and intestinal microbiota that usually act interdependently. An increased understanding of the mechanisms underlying obesity-GI cancer link can provide multiple opportunities for cancer prevention. This review discusses various mechanisms involved molecular mechanisms linking obesity with GI cancers including esophagus, stomach, colorectal and hepatocellular. Furthermore, an optional intervention such as diet restriction and exercise is described, which may be preventive or therapeutic in GI cancer. | 10.4103/ijpvm.IJPVM_266_20 |
pubmed_394_20410 | A sugar beet (Beta vulgaris) fosmid library from the doubled haploid accession KWS2320 encompassing 115 200 independent clones was constructed and characterized. The average insert size of the fosmid library was determined by pulsed field gel electrophoresis to be 39 kbp on average, thus representing 5.9-fold coverage of the sugar beet genome (758 Mbp). PCR screening of plate pools with primer pairs against nine sugar beet genes supported the insert size estimation. BLAST searches with 2951 fosmid end-sequences originating from 1510 clones (1536 clones attempted) revealed little contamination with organellar DNA (2.1% chloroplast DNA, 0.3% mitochondrial DNA). The sugar beet fosmid library will be integrated in the presently ongoing efforts to determine the sequence of the sugar beet genome. Fosmids will be publicly available in the format of plate pools and individual clones. | 10.1139/G08-071 |
pubmed_996_9862 | The effects of age and ethanol exposure on liver DNA single-strand breaks (SSB) and liver cell injury induced in hamsters and rats by a single equimolar dose (0.39 mmol/kg) of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) or N-nitrosodimethylamine (NDMA) were investigated. NNK induced more DNA SSB (by 10-50%) than NDMA in the liver of adult hamsters and rats, but similar differences were not observed in newborn animals. Nitrosamine-induced hepatic DNA damages was compared in newborn and adult animals. While newborn hamsters were less sensitive to NNK-induced DNA damage than adult hamsters, newborn rats were more sensitive to NDMA-induced DNA damage than adult rats. In utero ethanol exposure did not alter significantly the induction of hepatic DNA SSB by NNK or NDMA compared to newborn hamsters and rats. Interestingly, species differences in the extents of NNK-induced hepatic DNA SSB and toxicity were observed in ethanol-consuming adult hamsters and rats. Ethanol treatment of hamsters caused a significant reduction (by 35%) of the frequency of hepatic DNA SSB and a 3.5-fold enhancement of hepatotoxicity induced by NNK. | 10.1016/0304-3835(93)90240-a |
pubmed_468_17702 | Histoplasmosis is a worldwide infectious disease caused by inhalation of spores of a fungus, called Histoplasma capsulatum.Adrenals can be involved as a part of disseminated infection in immunocompromized patients. However, histoplasmosis presenting primarily as a bilateral adrenal masses in an immunocompetent patient is very unusual and rare. We encountered three such cases in which fine-needle aspiration (FNA) performed under ultrasonographic (USG) guidance from bilateral adrenal masses primarily established the diagnosis. This report emphasizes the importance of considering localized fungal infection as differential diagnoses of mass lesions involving bilateral adrenals even if the patients are immunocompetent, along with the commoner lesions at these sites. | 10.1002/dc.21660 |
pubmed_590_981 | The HIV-1 Nef virulence factor interacts with multiple host cell-signaling proteins. Nef binds to the Src homology 3 domains of Src family kinases, resulting in kinase activation important for viral infectivity, replication, and MHC-I down-regulation. Itk and other Tec family kinases are also present in HIV target cells, and Itk has been linked to HIV-1 infectivity and replication. However, the molecular mechanism linking Itk to HIV-1 is unknown. In this study, we explored the interaction of Nef with Tec family kinases using a cell-based bimolecular fluorescence complementation assay. In this approach, interaction of Nef with a partner kinase juxtaposes nonfluorescent YFP fragments fused to the C terminus of each protein, resulting in YFP complementation and a bright fluorescent signal. Using bimolecular fluorescence complementation, we observed that Nef interacts with the Tec family members Bmx, Btk, and Itk but not Tec or Txk. Interaction with Nef occurs through the kinase Src homology 3 domains and localizes to the plasma membrane. Allelic variants of Nef from all major HIV-1 subtypes interacted strongly with Itk in this assay, demonstrating the highly conserved nature of this interaction. A selective small molecule inhibitor of Itk kinase activity (BMS-509744) potently blocked wild-type HIV-1 infectivity and replication, but not that of a Nef-defective mutant. Nef induced constitutive Itk activation in transfected cells that was sensitive to inhibitor treatment. Taken together, these results provide the first evidence that Nef interacts with cytoplasmic tyrosine kinases of the Tec family and suggest that Nef provides a mechanistic link between HIV-1 and Itk signaling in the viral life cycle. | 10.1074/jbc.M114.572099 |
pubmed_288_9182 | DNA-binding functionality among transcription factor proteins is afforded by a number of structural motifs, such as the helix-turn-helix, helix-loop-helix, and zinc finger domains. The common thread among these diverse structures is their sequence-specific binding to essential promoter or other genetic regulatory sequences with high selectivity and affinity. One such motif, present in a wide range of organisms from bacteria to vertebrates, is the Gata-type zinc finger. This family of DNA-binding proteins is characterized by the presence of one or two (Cys)(4) metal binding sites which recognize the protein's eponymous binding site, GATA. Unlike other conserved DNA-binding domains, Gata proteins appear to be restricted to binding consensus GATA sequences, or near variations, in DNA. Since the architecture of the Gata finger seems built around recognizing this particular sequence, we set out to define the allowable range of amino acid substitutions along the DNA-binding surface of a Gata finger that could continue to support sequence-specific DNA-binding activity. Accordingly, we set up a one-hybrid screen in yeast based on the chicken Gata-1 C-terminal zinc finger. Mutant libraries were generated at five amino acids identified in the Gata-DNA structure as likely to mediate sequence-specific contacts between the Gata finger and DNA. These libraries were designed to give as exhaustive amino acid coverage as possible such that almost all alternative amino acids were screened at each of the five probed positions. Screening and characterization of these libraries revealed several functional amino acid substitutions at two leucines which contact the DNA at the 3' and 5' flanks of the GATA binding site, but no functional substituents for amino acids near the core of the binding site. This pattern is consistent with amino acid sequences of known DNA-binding Gata fingers. | 10.1016/j.bbrc.2008.02.136 |
pubmed_1134_11123 | Fungal bloodstream infection (BSI) is of increasing concern in the hospital environment. This study compared routine hospital discharge data at two inner Sydney hospitals with a pathology database over a 6-year period. A high level of underreporting was found, with only 42% of the pathology database cases assigned an appropriate code in the hospital discharge data despite evidence of the infection being found in 97% of the medical records identified from the pathology database. The location of the evidence in the medical record had an impact on whether or not the infection was assigned a code. There was a greater likelihood that a code would be assigned if the infection was documented on the front sheet of the medical record. Improvements can be made to the reporting of fungal BSI if clinicians record it on the front sheet and if coders review the whole medical record before coding. | 10.1177/183335830503400306 |
pubmed_223_24105 | BACKGROUND
Intracerebral hemorrhage (ICH) is the common brain diseases in middle-aged and elderly people, with high disability and/or mortality rate, and is a serious public health concern. Both WNK3 kinase and the WNK3/SPAK/NKCC1 signaling pathway play an integral role in maintaining normal cell homeostasis. However, their role and underlying mechanisms in ICH-induced secondary brain injury (SBI) have yet to be elucidated.
METHODS
We established an ICH model using male Sprague-Dawley (SD) rats by injecting autologous arterial blood into the unilateral basal ganglia. To establish ICH model in vitro, oxyhemoglobin (OxyHb; 20 μM) and neurons were cultured for 6 h at 37 °C, 5% CO2 atmosphere. To investigate the role of WNK3 and the WNK3/SPAK/NKCC1 signaling pathway in SBI, after genetic interventions, rotation and water maze test, brain edema and neuroinflammation were detected, and terminal-deoxynucleoitidyl transferase mediated dUTP nick end labeling (TUNEL), Fluoro-Jade C (FJC), and Nissl staining were performed.
RESULTS
Our data showed that WNK3 expression in brain tissue were upregulated after ICH induction. In addition, silencing of WNK3 reduced neuronal apoptosis, and inflammatory responses in rats that underwent ICH. Inhibition of WNK3 expression reduced the damaged blood-brain barrier (BBB), alleviated the impaired degree of cerebral edema, and improved disruptive neurobehavioral cognition caused by ICH. Moreover, overexpression of WNK3 had the opposite effects. Finally, WNK3/SPAK/NKCC1 signaling pathway may be involved in the above-mentioned processes.
CONCLUSIONS
In conclusion, our findings showed that WNK3 and WNK3/SPAK/NKCC1 signaling pathway play a vital biological function in ICH-induced SBI. Depletion of WNK3 attenuated brain injury after ICH both in vivo and in vitro. Thus, WNK3 and WNK3/SPAK/NKCC1 signaling pathway are potential targets for treating SBI after ICH. | 10.1016/j.expneurol.2020.113386 |
pubmed_507_433 | With the increasing application of various genomic technologies in biomedical research, there is a need to integrate these data to correlate candidate genes/regions that are identified by different genomic platforms. Although there are tools that can analyze data from individual platforms, essential software for integration of genomic data is still lacking. Here, we present a novel Java-based program called CGI (Cytogenetics-Genomics Integrator) that matches the BAC clones from array-based comparative genomic hybridization (aCGH) to genes from RNA expression profiling datasets. The matching is computed via a fast, backend MySQL database containing UCSC Genome Browser annotations. This program also provides an easy-to-use graphical user interface for visualizing and summarizing the correlation of DNA copy number changes and RNA expression patterns from a set of experiments. In addition, CGI uses a Java applet to display the copy number values of a specific BAC clone in aCGH experiments side by side with the expression levels of genes that are mapped back to that BAC clone from the microarray experiments. The CGI program is built on top of extensible, reusable graphic components specifically designed for biologists. It is cross-platform compatible and the source code is freely available under the General Public License. | pubmed_507_433 |
pubmed_377_15431 | We have demonstrated that an Arabidopsis serine/arginine rich-like protein, atSR45a, interacts with other splicing factors and its expression is markedly induced by high-light stress, suggesting the involvement of atSR45a in the regulation of stress-responsive alternative splicing. A whole-genome tiling array identified the alternative splicing of genes regulated by atSR45a by comparing gene expression profiles in wild-type and knockout atSR45a (KO-sr45a) plants under high-light stress. The expression levels of genomic regions within 217 genes were significantly altered in the KO-sr45a plants compared with the wild-type plants. Many genes encoded factors involved in signal transduction, cell cycle and DNA processing, protein fate and transcription. A semi-quantitative reverse transcription-PCR (RT-PCR) analysis confirmed changes in the transcript levels and/or alternative splicing efficiency under high-light stress in 18 genes, suggesting that atSR45a affects directly or indirectly not only alternative splicing efficiency but also the transcription of these target genes. Changes in the expression of atSR45a in response to high-light stress temporally correlated with changes in the alternative splicing efficiency and transcript levels of three and one target genes, respectively. Sequencing of the alternatively spliced variants of three target genes showed that atSR45a suppresses the splicing efficiency of intron retention-type alternative splicing events. These findings indicated the importance of atSR45a to the diversification of the transcriptome under high-light stress. | 10.1093/pcp/pcr115 |
pubmed_22_13574 | The phenomenon of "digital divide" is complex and multidimensional, extending beyond issues of physical access. The purpose of this study was to develop a scale to measure a range of factors related to digital divide among higher education faculty and to evaluate its reliability and validity. Faculty's Information and Communication Technology Access (FICTA) scale was tested and validated with 322 faculty teaching in public and private sector universities. Principal components analysis with varimax rotation confirmed an 8-factor solution corresponding to various dimensions of ICT access. The 57-item FICTA scale demonstrated good psychometric properties and offers researchers a tool to examine faculty's access to ICT at four levels - motivational, physical, skills, and usage access. | 10.1007/s10639-017-9599-9 |
pubmed_403_4257 | The transport of eroded soil to rivers changes the nutrient cycles of river ecosystems and has significant impacts on the regional eco-environment and human health. The Loess Plateau, a leading vegetation restoration region in China and the world, has experienced severe soil erosion and nutrient loss, however, the extent to which vegetation restoration prevents soil erosion export (to rivers) and it caused nutrient loss is unknown. To evaluate the effects of the first stage of the Grain for Green Project (GFGP) on the Loess Plateau (started in 1999 and ended in 2013), we analyzed the vegetation change trends and quantified the effects of GFGP on soil erosion export (to rivers) and it caused nutrient loss by considering soil erosion processes. The results were as follows: (1) in the first half of study period (from 1982 to 1998), the vegetation cover changed little, but after the implementation of the first stage of the GFGP (from 1999 to 2013), the vegetation cover of 75.0% of the study area showed a significant increase; (2) The proportion of eroded areas decreased from 41.8 to 26.7% as a result of the GFGP, and the erosion intensity lessened in most regions; the implementation significantly reduce the soil nutrient loss; (3) at the county level, soil erosion export could be avoided significantly by the increasing of vegetation greenness in the study area (R = -0.49). These results illustrate the relationships among changes in vegetation cover, soil erosion and nutrient export, which could provide a reference for local government for making ecology-relative policies. | 10.3389/fpls.2020.573126 |
pubmed_827_18329 | A rheo-optical methodology, based on small angle light scattering and transmitted light intensity measurements, has been used to study in situ and on a time resolved basis the shear induced morphology in ternary two-phase water-gelatin-dextran mixtures. Emulsions close to the binodal line as well as far from it have been investigated. It is shown that above a critical shear rate, shear-induced mixing occurs at the length scales probed by the laser light. It is hypothesized that the shear-induced homogenization is due to the shear forces that exceed the intermolecular forces of the self-association process of the gelatin. The isothermal phase diagram at a fixed shear rate has been determined. In addition, the structure evolution after cessation of flow has been studied. When flow is stopped after homogenization, phase separation occurs almost instantaneously. When subsequently applying a low shear rate, the structure coarsens due to coalescence of the dispersed droplets. The kinetics of this coalescence process is strain controlled. | 10.1021/bm0300352 |
pubmed_518_20136 | Hyperthermia produces regression of human cancer. Because hyperthermia has produced only limited results, attention has focused on searching for substances able to sensitize tumour cells to the effects of hyperthermia. The flavonoid quercetin has been reported to be a hyperthermic sensitizer in ovarian and uterine cervical tumours and in leukaemia. Quercetin and tamoxifen inhibit melanoma cell growth. We therefore investigated whether quercetin and tamoxifen can sensitize M10, M14 and MNT1 human melanoma cells to hyperthermia. We observed that both quercetin and tamoxifen synergize with hyperthermia (42.5 degrees C) in reducing the clonogenic activity of M14 and MNT1 and in inducing apoptotic cell death in all three cell lines. As revealed by flow cytometric and Northern blot analyses, quercetin and tamoxifen reduced heat shock protein-70 expression at both protein and mRNA levels. Our results suggest that quercetin and tamoxifen can be usefully combined with hyperthermia in the therapy of recurrent and/or metastatic melanoma. | 10.1097/00008390-200110000-00005 |
pubmed_456_24873 | There are medical indications in pregnancy for which there is evidence or expert opinion to support delivery versus expectant management in the early-term period. However, the risk of adverse outcomes is greater for neonates delivered in the early-term period compared with neonates delivered at 39 weeks of gestation. In addition to immediate adverse perinatal outcomes, multiple studies have shown increased rates of adverse long-term infant outcomes associated with late-preterm and early-term delivery compared with full-term delivery. A recent systematic review found that late-preterm and early-term children have lower performance scores across a range of cognitive and educational measures compared with their full-term peers. Further research is needed to better understand if these differences are primarily based on gestational age at delivery versus medical indications for early delivery. Documentation of fetal pulmonary maturity alone does not necessarily indicate that other fetal physiologic processes are adequately developed. For this reason, amniocentesis for fetal lung maturity is not recommended to guide timing of delivery, even in suboptimally dated pregnancies. Avoidance of nonmedically indicated delivery before 39 0/7 weeks of gestation is distinct from, and should not result in, an increase in expectant management of patients with medical indications for delivery before 39 0/7 weeks of gestation. Management decisions, therefore, should balance the risks of pregnancy prolongation with the neonatal and infant risks associated with early-term delivery. Although there are specific indications for delivery before 39 weeks of gestation, a nonmedically indicated early-term delivery should be avoided. This document is being revised to reflect updated data on nonmedically indicated early-term deliveries. | 10.1097/AOG.0000000000003077 |
pubmed_405_12471 | Replicating the nanostructured components of extracellular matrix is a target for dermal tissue engineering and regenerative medicine. Electrospinning Bombyx mori silk fibroin (BMSF) allows the production of nano- to microscale fibrous scaffolds. For BMSF electrospun scaffolds to be successful, understanding and optimizing the cellular response to material morphology is essential. Primary human dermal fibroblast response to nine variants of BMSF scaffolds composed of nano- to microscale fibers ranging from ~250 to ~1200 nm was assessed in vitro with regard to cell proliferation, viability, cellular morphology, and gene expression. BMSF support of epithelial migration was then assessed through utilization of a novel ex vivo human skin wound healing model. Scaffolds composed of the smallest diameter fibers, ~250 -300 nm, supported cell proliferation significantly more than fibers with diameters approximately 1 μm (p < 0.001). Cell morphology was observed to depart from a stellate morphology with numerous cell -fiber interactions to an elongated, fiber-aligned morphology with interaction predominately with single fibers. The expressions of extracellular matrix genes, collagen types I and III (p < 0.001), and proliferation markers, proliferating cell nuclear antigen (p < 0.001), increased with decreasing fiber diameter. The re-epithelialization of ex vivo wound models was significantly improved with the addition of BMSF electrospun scaffolds, with migratory keratinocytes incorporated into scaffolds. BMSF scaffolds with nanofibrous architectures enhanced proliferation in comparison to microfibrous scaffolds and provided an effective template for migratory keratinocytes during re-epithelialization. The results may aid in the development of effective BMSF electrospun scaffolds for wound healing applications. | 10.1177/2041731414551661 |
pubmed_779_1929 | Currently, limited information regarding the role of calcitonin gene-related peptide (CGRP) in neuropathic pain is available. Intracerebroventricular administrations of an anti-CGRP antibody were performed in rats with infraorbital nerve ligation. Anti-CGRP antibody administration attenuated mechanical and heat hypersensitivities induced by nerve ligation and decreased the phosphorylated extracellular signal-regulated kinase expression levels in the trigeminal spinal subnucleus caudalis (Vc) following mechanical or heat stimulation. An increased CGRP immunoreactivity in the Vc appeared after nerve ligation. A decreased CGRP immunoreactivity resulted from anti-CGRP antibody administration. Our findings suggest that anti-CGRP antibody administration attenuates the symptoms of trigeminal neuropathic pain by acting on CGRP in the Vc. | 10.1016/j.bbrc.2021.07.001 |
pubmed_122_8988 | BACKGROUND
Patterns of homozygosity can be influenced by several factors, such as demography, recombination, and selection. Using the goat SNP50 BeadChip, we genotyped 3171 goats belonging to 117 populations with a worldwide distribution. Our objectives were to characterize the number and length of runs of homozygosity (ROH) and to detect ROH hotspots in order to gain new insights into the consequences of neutral and selection processes on the genome-wide homozygosity patterns of goats.
RESULTS
The proportion of the goat genome covered by ROH is, in general, less than 15% with an inverse relationship between ROH length and frequency i.e. short ROH (< 3 Mb) are the most frequent ones. Our data also indicate that ~ 60% of the breeds display low FROH coefficients (< 0.10), while ~ 30 and ~ 10% of the goat populations show moderate (0.10 < FROH < 0.20) or high (> 0.20) FROH values. For populations from Asia, the average number of ROH is smaller and their coverage is lower in goats from the Near East than in goats from Central Asia, which is consistent with the role of the Fertile Crescent as the primary centre of goat domestication. We also observed that local breeds with small population sizes tend to have a larger fraction of the genome covered by ROH compared to breeds with tens or hundreds of thousands of individuals. Five regions on three goat chromosomes i.e. 11, 12 and 18, contain ROH hotspots that overlap with signatures of selection.
CONCLUSIONS
Patterns of homozygosity (average number of ROH of 77 and genome coverage of 248 Mb; FROH < 0.15) are similar in goats from different geographic areas. The increased homozygosity in local breeds is the consequence of their small population size and geographic isolation as well as of founder effects and recent inbreeding. The existence of three ROH hotspots that co-localize with signatures of selection demonstrates that selection has also played an important role in increasing the homozygosity of specific regions in the goat genome. Finally, most of the goat breeds analysed in this work display low levels of homozygosity, which is favourable for their genetic management and viability. | 10.1186/s12711-018-0424-8 |
pubmed_905_13485 | BACKGROUND
The advantages of reduced-port laparoscopic surgery (RPLS) for rectosigmoid cancer treatment have been disputed. This study evaluated the outcomes of RPLS compared to conventional laparoscopic surgery (CLS) for rectosigmoid cancer.
METHODS
Data from 211 patients who underwent a selective sigmoidectomy or anterior resection from August 2011 to June 2014 at a single institution were collected and analyzed via propensity score matching. Operative outcomes, inflammatory responses, pain intensity, oncologic outcomes, quality of life, and cosmetic results were compared between groups.
RESULTS
After matching, 96 patients (48 CLS and 48 RPLS) were evaluated. Sixteen RPLS cases underwent single-incision laparoscopic surgery (SILS), and 32 underwent single-incision plus one port laparoscopic surgery (SILS + 1). Baseline clinical characteristics were comparable between the RPLS and the CLS groups. Morbidity, pathologic outcomes, and 3-year disease-free survival and overall survival rates were also comparable between the 2 groups. Compared with the CLS group, the RPLS group had a shorter total incision length (p < 0.001); shorter time to liquid diet (p = 0.027), ambulation (p = 0.026), and discharge (p < 0.001); and lower visual analogue scale scores during mobilization at postoperative days 3-5 (p < 0.05). The total operation times, C-reactive protein levels at 24 h and 96 h, and interleukin-6 levels at 24 h postoperatively were significantly lower in the SILS + 1 group than those in the CLS and SILS groups (p < 0.05). Compared with the CLS group, the RPLS group showed better social functioning at 6 months postoperatively (p = 0.011). The SILS and SILS + 1 groups showed similar cosmetic results, and both groups showed better results than the CLS group (p < 0.001).
CONCLUSIONS
RPLS for rectosigmoid cancer is feasible, with short-term safety and long-term oncological safety comparable to that of CLS. Better cosmesis and accelerated recovery can be expected. SILS + 1 is a better choice than CLS or SILS for rectosigmoid cancer because it minimizes invasiveness and reduces technical difficulties. | 10.1007/s00464-016-5244-8 |
pubmed_125_1894 | Channelrhodopsin-2 (ChR2) is an ion channel activated by the absorption of light. A recent experiment demonstrated that the current emanating from neurons in live brain cells expressing ChR2 can be controlled using two-photon phase control. Here, we propose an experimentally testable coherent control mechanism for this phenomenon. Significantly, we describe how femtosecond, quantum coherent processes arising from weak-field ultrafast excitation are responsible for the reported control of the millisecond classical dynamics of the neuronal current. | 10.1063/5.0012642 |
pubmed_121_20565 | This review considers alternative protein sources through the analysis of food science literature and patents. Data collection was performed from scientific literature and patent documents using the Scopus and National Institute of Industrial Property databases, with a term combination "alternative protein source" and "source* AND protein* AND alternative*". A total of 945 documents were analyzed. The scientific prospection showed that agricultural and biological science was the main application area. The food industry area had the highest number of filed patents. The annual evaluation of published documents demonstrated that this area had been investigated since the 1970s, and the number of articles was twice than that of filled patents. Although protein products are available for sale, animal and vegetable sources replace conventional protein products. Presently, alternative protein sources are already a worldwide trend in the food industry, enabling the development of new products to facilitate their insertion into the consumer market. | 10.1016/j.foodchem.2022.133486 |
pubmed_1122_19192 | Murine studies have demonstrated that the presence of indigenous gut flora is crucial for the induction of systemic immune hyporesponsiveness to antigens initially encountered within the gastrointestinal lumen. This study investigated whether increased titers of such flora, as occur in human small intestinal bacterial overgrowth, may be associated with increased suppression of systemic immune responsiveness and the possible relation between systemic and mucosal immunity in this setting. Serum total immunoglobulin (Ig), immunoglobulin subclass, and soluble interleukin-2 receptor levels and lamina propria IgA plasma cell counts were determined in 50 consecutive subjects with (N = 30) and without (N = 20) small intestinal bacterial overgrowth. Luminal IgA levels were measured in 35 of these subjects. Serum concentrations of IgG3, but not of other immunoglobulin isotypes or soluble interleukin-2 receptors, were significantly reduced in subjects with bacterial overgrowth (P < 0.0005). Small intestinal lamina propria IgA plasma cell counts (P < 0.0005) and luminal IgA concentrations (P = 0.001) were significantly increased in this group. Serum IgG3 levels were significantly inversely correlated with luminal IgA levels (P < 0.01) and fell below the lower limit of normal (0.41 g/liter) in 17/30 (56.7%) subjects with bacterial overgrowth compared to 1/20 (5.0%) subjects without (P < 0.0005). These findings document an association between small intestinal bacterial overgrowth with indigenous gut flora and reduced serum IgG3 reactivity in humans, possibly via an interaction with mucosa-related immunoregulatory mechanisms. The possibility of underlying small intestinal bacterial overgrowth should be considered in patients with serum IgG3 deficiency, especially those with compatible symptoms and/or known predisposition. | 10.1023/a:1026652412554 |
pubmed_135_6258 | Morphological or behavioral defense mechanisms are important evolutionary strategies for the survival of prey. Studies have focused on predation and competition, but infection has been overlooked, despite being a determining factor of distribution and species diversity of prey. We hypothesized that the winter migration of Daphnia pulicaria is a community defense strategy to avoid fungal infection. To test this hypothesis, environmental variables and the Cladocera community, including D. pulicaria, were monitored in three study sections of the Anri Reservoir in the Republic of Korea during September 2010-August 2015. During three winter seasons, the density of infected D. pulicaria increased in all study sections, and they migrated from the central to the littoral area. Most of the infected individuals had dormant eggs in sexually reproducing mothers. However, when the proportion of non-infected individuals was higher than that of infected individuals, winter migration was not observed. Additional microcosm experiments showed that dormant eggs of D. pulicaria obtained from ice crystals in the littoral area had lower hatching and infection rates than those obtained from mothers moving from other zones. Therefore, the migration of D. pulicaria during winter is an active response to avoid intergenerational fungal infection. | 10.3390/biology11101409 |
pubmed_409_9767 | Many dream reports, which take the form of propositional speech, are more meaningful if understood as metaliteral speech. To achieve this understanding the speech sounds must be decoded according to different linguistic rules than govern propositional speech. The basic rules for metaliteral speech were outlined in a recent paper. Those rules came from empirical observation. This paper proposes that the right hemisphere is dominant for the linguistic activity of metaliteral speech because, in one way or another, the rules all seem to depend on the cognitive use of right hemisphere functions, or sometimes, on the absence of left hemisphere functions. The proposed theory rejects an exclusive role for the right hemisphere in metaliteral behavior. By recognizing the subordinate role of the left, the puzzles are solved of the story-like quality to dream reports and the central role of prosody in decoding metaliteral speech. | pubmed_409_9767 |
pubmed_588_11477 | Novel hierarchical nanostructures based on ionically self-assembled complexes of diblock copolypeptides and surfactants are presented. Rod-coil diblock copolypeptide poly(gamma-benzyl-L-glutamate)-block-poly(L-lysine), PBLG-b-PLL (Mn = 25,000 and 8000 for PBLG and PLL, respectively, polydispersity index 1.08), was complexed with anionic surfactants dodecanesulfonic acid (DSA) or dodecyl benzenesulfonic acid (DBSA), denoted as PBLG-b-PLL(DSA)1.0 and PBLG-b-PLL(DBSA)1.0, respectively. The complexation leading to supramolecular rod-comb architectures was studied by transmission electron microscopy (TEM), small-angle X-ray scattering (SAXS), Fourier transform infrared spectroscopy (FTIR), and polarized optical microscopy (POM). PBLG-b-PLL, PBLG-b-PLL(DBSA)1.0, and PBLG-b-PLL(DSA)1.0 self-assemble with alternating PBLG lamellae and PLL-containing lamellae with a periodicity of 27-33 nm. Within the PBLG lamellae, the rod-like PBLG helices pack with a periodicity of ca. 1.3 nm. The internal structure of the PLL-containing lamellae depends on the complexation. For pure PBLG-b-PLL, the PLL chains adopt a random coil conformation and the PLL domains are disordered. For PBLG-b-PLL(DSA)1.0, lamellar self-assembly of periodicity of 3.7 nm within the PLL(DSA)1.0 domains is observed due to crystalline packing of the linear n-dodecyl tails. For PBLG-b-PLL(DBSA)1.0 with branched dodecyl tails, a distinct SAXS reflection is observed, suggesting self-assembly within the PLL(DBSA)1.0 domains with a periodicity of 2.9 nm. However, due to the absence of higher order reflections, the internal structure cannot be conclusively assigned. The efficient plasticization which leads to fluid-like liquid crystallinity in PBLG-b-PLL(DBSA)1.0 and an alpha-helical conformation according to FTIR allows us to suggest that the PLL(DBSA)1.0 domains have a hexagonal internal structure. The interplay of self-assembly at different length scales combined with rod-like liquid crystallinity can open new routes to design functional materials. | 10.1021/bm0606770 |
pubmed_357_19642 | Successfully embedding researchers in a health care setting brings unique challenges and opportunities. Through a joint clinical and academic partnership, we have developed a novel approach to problem-solving in the health care context, by employing a model for leading through change to embed researchers in transformative initiatives. Using the model, we have been able to leverage our local environment and resources to engage multi-disciplinary researchers in solving complex issues. An example is our initiative, Enhancing the Practice of Medicine, to address burnout among health care providers. Through this work, we have identified 3 primary factors critical to the successful deployment of embedded researchers. First and foremost, a multi-disciplinary team with diverse expertise is necessary to truly understand the root causes and potential solutions for complex issues. Second, this diverse team of embedded researchers must be involved from the initial stages of project design and have a voice throughout all phases of planning and assessing the initiative. Finally, embedded researchers will be most successful when they are supported to build relationships, navigate the system, and conduct research as part of an integrated and comprehensive effort that aligns with health system priorities. | 10.1016/j.hjdsi.2020.100492 |
pubmed_561_21540 | Stimulation of the brain CCK2 receptor by the C-terminal octapeptide CCK8 of cholecystokinin (CCK) negatively modulates opioid responses. This suggests the existence of physiologically relevant interactions between endogenous CCK and opioid peptides, opening new perspectives particularly in the treatment of pain or drug addiction. CCK2 receptor-deficient mice were used to analyze the incidence of this gene invalidation on opioid system. Compared with wild-type mice, mutants exhibited the following: (1) a hypersensitivity to the locomotor activity induced by inhibitors of enkephalin catabolism or by morphine; (2) a spontaneous hyperalgesia to thermal nociceptive stimulus, which was reversed by previous administration of the NMDA antagonist MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate], and a large reduction in analgesic effects of endogenous or exogenous opioids; and (3) a more severe withdrawal syndrome after chronic morphine treatment. As expected, stimulation of mu, delta, and D2 receptors on brain tissue of wild-type animals induced a dose-dependent decrease in adenylate cyclase activity, whereas a striking mirror effect was observed in mutants. All of these results suggest that the absence, in knock-out mice, of the negative feedback control on the opioid system, normally performed out by CCK2 receptor stimulation, results in an upregulation of this system. These biochemical and pharmacological results demonstrate the critical role played by CCK2 receptors in opioid-dependent responses. | pubmed_561_21540 |
pubmed_87_16101 | Methionine-enkephalin (M-ENK) and leucine-enkephalin (L-ENK) are small endogenous opioid peptides that have been implicated in a wide variety of complex physiological functions, including nociception, reward processing, and motivation. However, our understanding of the role that these molecules play in modulating specific brain circuits remains limited, largely due to challenges in determining where, when, and how specific neuropeptides are released in tissue. Background-subtracted fast-scan cyclic voltammetry coupled with carbon-fiber microelectrodes has proven to be sensitive and selective for detecting rapidly fluctuating neurochemicals in vivo; however, many challenges exist for applying this approach to the detection of neuropeptides. We have developed and characterized a novel voltammetric waveform for the selective quantification of small tyrosine-containing peptides, such as the ENKs, with rapid temporal (subsecond) and precise spatial (10s of micrometers) resolution. We have established that the main contributor to the electrochemical signal inherent to M-ENK is tyrosine and that conventional waveforms provide poor peak resolution and lead to fouling of the electrode surface. By employing two distinct scan rates in each anodic sweep of this analyte-specific waveform, we have selectively distinguished M-ENK from common endogenous interfering agents, such as ascorbic acid, pH shifts, and even L-ENK. Finally, we have used this approach to simultaneously quantify catecholamine and M-ENK fluctuations in live tissue. This work provides a foundation for real-time measurements of endogenous ENK fluctuations in biological locations, and the underlying concept of using multiple scan rates is adaptable to the voltammetric detection of other tyrosine-containing neuropeptides. | 10.1021/ac501725u |
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