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pubmed_588_17760 | Sudden cardiac death is the most devastating complication of hypertrophic cardiomyopathy. Since HCM may present at young age, and since the risk period for sudden arrhythmic death may be long, decision-making in HCM patients may be difficult, and have lifelong implications. Community based studies show a sudden death mortality of approximately 1%/year. Certain patients can be identified by their clinical characteristics, and through testing, to have higher annual risk, as high as 4-5%/year. Risk factors sudden cardiac death include: family history of HCM and sudden death, recurrent syncope, ventricular tachycardia, as detected by Holter monitoring or exercise testing, subnormal (<20 mmHg) increase in systolic blood pressure on maximal exercise testing and lastly marked (especially >30 mm) left ventricular hypertrophy. The implantable defibrillator has been shown to avert sudden death in selected HCM patients deemed to be at high risk. | pubmed_588_17760 |
pubmed_188_18300 | Salmonella enterica serovar Typhimurium is one of approximately 2,500 distinct serovars of the genus Salmonella but is exceptional in its wide distribution in the environment, livestock, and wild animals. S Typhimurium causes a large proportion of nontyphoidal Salmonella (NTS) infections, accounting for a quarter of infections, second only to S. enterica serovar Enteritidis in incidence. S Typhimurium was once considered the archetypal broad-host-range Salmonella serovar due to its wide distribution in livestock and wild animals, and much of what we know of the interaction of Salmonella with the host comes from research using a small number of laboratory strains of the serovar (LT2, SL1344, and ATCC 14028). But it has become clear that these strains do not reflect the genotypic or phenotypic diversity of S Typhimurium. Here, we review the epidemiological record of S Typhimurium and studies of the host-pathogen interactions of diverse strains of S Typhimurium. We present the concept of distinct pathovariants of S Typhimurium that exhibit diversity of host range, distribution in the environment, pathogenicity, and risk to food safety. We review recent evidence from whole-genome sequencing that has revealed the extent of genomic diversity of S Typhimurium pathovariants, the genomic basis of differences in the level of risk to human and animal health, and the molecular epidemiology of prominent strains. An improved understanding of the impact of genome variation of bacterial pathogens on pathogen-host and pathogen-environment interactions has the potential to improve quantitative risk assessment and reveal how new pathogens evolve. | 10.1128/IAI.00079-18 |
pubmed_463_17037 | In this study, we examined 615 host genes encoding 915 in-miRNAs as possible targets for interactions with all in-miRNAs. Host genes whose proteins are involved in esophageal, gastric, small bowel, colorectal, and breast cancer development were studied. Unique in-miRNA binding sites with a significance of p<0.0005 were found in the 5'UTRs, CDSs, and 3'UTRs of the host genes encoding proteins that are key participants in tumourigenesis. These data shed light on the interactions between miRNAs and mRNAs and on the role of candidate proteins in cancer. Therefore, our findings have potential application in the development of diagnostic and treatment methods. | pubmed_463_17037 |
pubmed_1078_544 | Using the tumor suppressor VHL protein as an example, we show that detailed analysis of conservation versus variation pattern in the multiple alignment can be coupled with the genomic pathway/complex conservation analysis to provide a more complete picture of the entire interaction/regulatory network. Results from the present study have allowed us to hypothesize that two additional proteins are involved in the VHL-mediated regulation of angiogenesis. Detailed modeling also has led to a prediction of the possible interaction mode between the known and the proposed parts of the VHL complex. To aid in an analysis of the VHL protein regulation of HIF-1 alpha degradation, an important and only partially understood process that directly influences angiogenesis, we performed a comprehensive search for the orthologs of the VHL as well as for VHL-interacting proteins in all the available eukaryotic genomes. Analysis of a multiple alignment of thus identified VHL orthologs reveals an unusually high degree of conservation of the surface amino acid residues that almost exactly correspond to positions mutated in the VHL disease-associated tumors. In addition, these positions form well-defined clusters in three-dimensional space, and presence or absence of individual clusters correlates with the presence or absence of pathway elements in different genomes. We have also shown that relation trees derived from the multiple sequence alignment, functional surface-mapping, and HIF-1 alpha degradation pathway structure are in complete agreement, linking the functional and structural evolution of the VHL protein and VHL-dependent HIF-1 alpha degradation complex. | 10.1110/ps.03454904 |
pubmed_462_4129 | Several studies in the literature have shown that DNA is damaged after UV irradiation in the presence of the sunscreen agent p-aminobenzoic acid (PABA), both in vivo and in vitro. One type of damage has been shown to be the result of increased yields of pyrimidine cyclobutane dimer formation. However, it has been suggested that other types of lesions are produced as well. We have studied the photochemistry of the thymine-PABA and thymidine-PABA systems and report here the isolation and characterization of thymine-PABA and thymidine-PABA photoadducts. These products have been identified, respectively, as 5-(2-amino-5-carboxyphenyl)-5,6-dihydrothymine and isomeric forms of 5-(2-amino-5-carboxyphenyl)-5,6-dihydrothymine. The quantum yields for the formation of these adducts in deaerated aqueous solutions at pH 7.0 have been determined to be 9.5 x 10(-4) and 4.3 x 10(-3) for the thymine and thymidine based adducts respectively. A pH profile for the thymine-PABA system indicated a maximum quantum yield for adduct formation at pH 6.5, although it could be detected over the whole pH range studied (pH 3.5-11.0). | 10.1111/j.1751-1097.1992.tb08507.x |
pubmed_1039_10379 | Plaque-forming cell (PFC) responses to sheep erythrocytes (SRBC) in cultures of spleen cells from mice with chronic Trypanosoma cruzi infections were found to be suppressed. Responses were restored with purified interleukin 2 (IL 2) and with supernatants that contained IL 2. Interleukin 1 (IL 1) prepared from the P338D1 hybridoma had no effect on in vitro responses when added alone, nor did it augment the effects of IL 2-rich supernatant. Interleukin X (IL X) generated from the FS7-20.6.18 T cell hybridoma was not effective alone or in combination with IL 1, nor were significant additive effects seen when IL X was combined with IL 2. The restorative effect of the IL 2-containing FS6-14.13 hybridoma supernatant (FS6-SN) was concentration dependent and was not seen when supernatant was added after day 1 of the culture period. Thus IL 2 alone, but not IL 1 or IL X, was able to reconstitute spleen cell responses of infected mice. In vivo anti-SRBC responses were also restored when mice were treated with IL 2-rich supernatant after immunization with SRBC. The immunologic defect in the production of PFC to heterologous erythrocytes by mice with chronic T. cruzi infections has been identified as a lack of functional help normally provided by the T cell product IL 2. | pubmed_1039_10379 |
pubmed_787_7307 | BACKGROUND
A randomized controlled trial performed by the Barcelona Clinic Liver Cancer (BCLC) published in 2002 demonstrated that transcatheter arterial chemoembolisation (TACE) is an effective treatment for well-selected patients with unresectable hepatocellular carcinoma (HCC).
AIM
To access whether this information has modified the use of TACE in clinical practice.
METHODS
From 2042 HCC patients included in the Italian Liver Cancer database, we selected 336 cases diagnosed over two 4-year periods (1999-2002, n = 161 and 2003-2006, n = 175), fulfilling the inclusion criteria of the BCLC study. These groups were compared for TACE application rate, patient characteristics and survival.
RESULTS
Patients undergoing TACE increased in the 2003-2006 period (from 62% to 73%, P = 0.035), with an increase in of Child-Pugh class A (from 64% to 77%, P = 0.048) and advanced HCC patients (from 54% to 69%, P = 0.041). In the 1999-2002 period, there was no significant difference in survival between TACE-treated and untreated patients, while in the 2003-2006 period, TACE-treated patients survived longer (P < 0.0001).
CONCLUSIONS
Following the publication of studies providing evidence of a survival benefit of TACE in selected patients with unresectable HCC, significantly more patients with well-compensated cirrhosis underwent TACE within this very homogenous population, leading to an increased survival despite a more advanced tumour stage. | 10.1111/j.1365-2036.2009.04198.x |
pubmed_347_2633 | Tailgut cysts are developmental hamartomas found in the presacral space. They are usually detected incidentally during physical examinations or imaging studies. However, they may cause symptoms due to compression of nearby organs. Due to their potential malignant transformation, surgical resection is warranted, while routine biopsy is considered controversial because of the concern about infection of the tailgut cyst and needle-track implantation of malignant cells. The co-existence of a carcinoid in a tailgut cyst is extremely rare. Only 16 cases have been reported previously, the vast majority of which were found in females. We herein present the case of a carcinoid in a tailgut cyst found in a male patient, discuss the potential pathogenesis of tailgut carcinoids, and underline the fact that their previous consideration of the condition as a female-restricted entity should be rejected. | 10.1007/s00595-012-0482-4 |
pubmed_968_2488 | Background: N6-methylandenosine-related long non-coding RNAs (m6A-related lncRNAs) are critically involved in cancer development. However, the roles and clinical significance of m6A-related lncRNAs in soft tissue sarcomas (STS) are inconclusive, thereby warranting further investigations. Methods: Transcriptome profiling data were extracted from The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx). Consensus clustering was employed to divide patients into clusters and Kaplan-Meier analysis was used to explore the prognostic differences between the subgroups. Gene set enrichment analysis (GSEA) was conducted to identify the biological processes and signaling pathways associated with m6A-Related lncRNAs. Finally, patients were randomly divided into training and validation cohorts, and least absolute shrinkage and selection operator (LASSO) Cox regression was conducted to establish the m6A-related lncRNA-based risk signature. Results: A total of 259 STS patients from TCGA-SARC dataset were enrolled in our study. Thirteen m6A-Related lncRNAs were identified to be closely related to the prognosis of STS patients. Patients were divided into two clusters, and patients in cluster 2 had a better overall survival (OS) than those in cluster 1. Patients in different clusters also showed differences in immune scores, infiltrating immune cells, and immune checkpoint expression. Patients were further classified into high-risk and low-risk subgroups according to risk scores, and high-risk patients were found to have a worse prognosis. The receiver operating characteristic (ROC) curve indicated that the risk signature displayed excellent performance at predicting the prognosis of patients with STS. Further, the risk signature was remarkably connected with the immune microenvironment and chemosensitivity in STS. Conclusion: Our study demonstrated that m6A-related lncRNAs were significantly associated with prognosis and tumor immune microenvironment and could function as independent prognosis-specific predictors in STS, thereby providing novel insights into the roles of m6A-related lncRNAs in STS. | 10.3389/fmolb.2021.715764 |
pubmed_1057_22096 | BACKGROUND
There has been much interest in environmental temperature and race as modulators of Coronavirus disease-19 (COVID-19) infection and mortality. However, in the United States race and temperature correlate with various other social determinants of health, comorbidities, and environmental influences that could be responsible for noted effects. This study investigates the independent effects of race and environmental temperature on COVID-19 incidence and mortality in United States counties.
METHODS
Data on COVID-19 and risk factors in all United States counties was collected. 661 counties with at least 50 COVID-19 cases and 217 with at least 10 deaths were included in analyses. Upper and lower quartiles for cases/100,000 people and halves for deaths/100,000 people were compared with t-tests. Adjusted linear and logistic regression analyses were performed to evaluate the independent effects of race and environmental temperature.
RESULTS
Multivariate regression analyses demonstrated Black race is a risk factor for increased COVID-19 cases (OR=1.22, 95% CI: 1.09-1.40, P=0.001) and deaths independent of comorbidities, poverty, access to health care, and other risk factors. Higher environmental temperature independently reduced caseload (OR=0.81, 95% CI: 0.71-0.91, P=0.0009), but not deaths.
CONCLUSIONS
Higher environmental temperatures correlated with reduced COVID-19 cases, but this benefit does not yet appear in mortality models. Black race was an independent risk factor for increased COVID-19 cases and deaths. Thus, many proposed mechanisms through which Black race might increase risk for COVID-19, such as socioeconomic and healthcare-related predispositions, are inadequate in explaining the full magnitude of this health disparity. | 10.1016/j.amjms.2020.06.015 |
pubmed_615_5868 | Simulations of supersonic turbulent flow over an open rectangular cavity are performed to observe the effects of length to depth ratio (L/D) of the cavity on the flow structure. Two-dimensional compressible time-dependent Reynolds-averaged Navier-Stokes equations with k-ω turbulence model are solved. A reduced order modeling approach, Proper Orthogonal Decomposition (POD) method, is used to further analyze the flow. Results are obtained for cavities with several L/D ratios at a Mach number of 1.5. Mostly, sound pressure levels (SPL) are used for comparison. After a reduced order modeling approach, the number of modes necessary to represent the systems is observed for each case. The necessary minimum number of modes to define the system increases as the flow becomes more complex with the increase in the L/D ratio. This study provides a basis for the control of flow over supersonic open cavities by providing a reduced order model for flow control, and it also gives an insight to cavity flow physics by comparing several simulation results with different length to depth ratios. | 10.1155/2013/810175 |
pubmed_611_23020 | The identification of genomic rearrangements involving more than 0.5 kb of the BRCA1 gene has confirmed a more complex mutation spectrum than was initially appreciated. Genomic rearrangements in BRCA1 represent 15% of all mutations in a group of French and American breast and ovarian cancer families and 36% of all mutations in a group of Dutch families. The rearrangements described to date range in size from 510 bp to 23.8 kb, are found throughout the gene, and are most frequently attributable to homologous recombination. We describe the identification of rearrangements in two breast and ovarian cancer families that involve 3.4 and 11.5 kb of the BRCA1 gene and span multiple exons but maintain the reading frame. Both gene rearrangements appear to result from Alu-mediated homologous recombination and have been detected by using a combination of protein truncation analysis and Southern blot analysis. These rearrangements result in the loss of amino acids that lie at the carboxy-terminus of the protein and that have previously been shown to have functional significance. Because these rearrangements result in the deletion of exons but maintain the reading frame, they may provide insights into specific regions and amino acids that have functional significance for the BRCA1 protein. | 10.1007/s004390000372 |
pubmed_374_25260 | AIM
This article aims to inform and share the experience of a Singaporean tertiary level neurosurgical unit in an academic medical centre during the COVID-19 outbreak.
METHOD
This is a descriptive study of our segregation team model which is designed with the aim of optimizing manpower and ensuring the safety and welfare of the neurosurgical unit, while maintaining and prioritizing excellent patient care.
RESULT
We describe our method of team segregation, rostering, and outline some principles that we adhere to in its design. We also summarise the restructuring of our inpatient and outpatient service, including the operating theatre and protocols for specific procedures, intensive care and general wards, as well as clinic services and multidisciplinary meetings.
CONCLUSION
We end with a commentary on residency training and anticipated challenges. Given the likely protracted course of the pandemic, it is key to account for sustainability of such measures and the conservation of resource via the reduction of pateint volume, upkeep of staff emotional and physical health and harnessing technologies such as telemedicine. | 10.1080/02688697.2020.1758629 |
pubmed_922_15832 | Pyrethroids are a class of widely-used insecticides that can be transported from terrestrial applications to aquatic systems via runoff and tend to sorb to organic carbon in sediments. Pyrethroid occurrence is detrimental to stream ecosystems due to toxicity to sediment-dwelling invertebrates which are particularly at risk of pyrethroid exposure in urban streams. In this work, 49 streams located in watersheds in the northeastern United States were surveyed for nine current-use pyrethroids using two extraction methods. Total sediment concentrations were determined by exhaustive chemical extraction, while bioaccessible concentrations were determined by single-point Tenax extraction. Total and bioaccessible pyrethroid concentrations were detected in 76% and 67% of the sites, and the average sum of pyrethroids was 232 ng/g organic carbon (OC) for total and 43.8 ng/g OC for bioaccessible pyrethroids. Bifenthrin was the most commonly detected pyrethroid in streambed sediments. Sediment toxicity was assessed using 10-d Hyalella azteca bioassays, and 28% and 15% of sediments caused a decrease in H. azteca biomass and survival, respectively. A temperature-based focused toxicity identification evaluation was used to assess pyrethroids as the causal factor for toxicity. The concentrations of pyrethroids was only weakly correlated with the degree of urban land use. Sediment toxicity was predicted by total and bioaccessible pyrethroid concentrations expressed as toxic units. This work suggests that bioaccessibility-based methods, such as Tenax extraction, can be a valuable tool in assessing sediment toxicity. | 10.1016/j.envpol.2019.07.099 |
pubmed_108_12035 | BACKGROUND
Physicians need a set of specific competences to perform well in interprofessional teams in their first year of residency. These competences should be achieved with graduation from medical school. Assessments during undergraduate medical studies are mostly rated by supervisors only. The aim of our study was to compare the rating of core facets of competence of medical students late in their undergraduate training as well as the rating confidence between three different groups of assessors (supervisors, residents, and nurses) in an assessment simulating the first day of residency.
METHODS
Sixty-seven advanced medical students from three different medical schools (Hamburg, Oldenburg and Munich) participated in a 360-degree assessment simulating the first working day of a resident. Each participant was rated by three assessors - a supervisor, a resident and a nurse - in seven facets of competence relevant for the first year of residency: (1) responsibility, (2) teamwork and collegiality, (3) knowing and maintaining own personal bounds and possibilities, (4) structure, work planning and priorities, (5) coping with mistakes, (6) scientifically and empirically grounded method of working, and (7) verbal communication with colleagues and supervisors. Means of all assessed competences and confidences of judgement of the three rating groups were compared. Additionally, correlations between assessed competences and confidence of judgement within each group of raters were computed.
RESULTS
All rating groups showed consistent assessment decisions (Cronbach's α: supervisors = .90, residents = .80, nurses = .78). Nurses assessed the participants significantly higher in all competences compared to supervisors and residents (all p ≤ .05) with moderate and high effect sizes (d = .667-1.068). While supervisors' and residents' ratings were highest for "teamwork and collegiality", participants received the highest rating by nurses for "responsibility". Competences assessed by nurses were strongly positively correlated with their confidence of judgment while supervisors' assessments correlated only moderately with their confidence of judgment in two competences.
CONCLUSIONS
Different professional perspectives provide differentiated competence ratings for medical students in the role of a beginning resident. Rating confidence should be enhanced by empirically derived behavior checklists with anchors, which need to be included in rater training to decrease raters' subjectivity. | 10.1186/s12909-019-1473-6 |
pubmed_426_10561 | With the aim of evaluating, in a controlled prospective fashion, the efficacy of monopolar electrocoagulation in the emergency treatment of bleeding gastric and stomal ulcers, 37 patients were studied: 16 were electrocoagulated (EC group) while the remaining 21 were treated by conventional methods (control group). The hemorrhage recurred in only one of the 16 patients belonging to the EC group, but in 11 of the 21 control patients (p less than 0.0005). Transfusion requirements were also reduced in the EC group (p less than 0.05), with no significant difference in relation to mortality. Stratifying the results according to hemorrhagic activity, electrocoagulation should be clearly effective in those patients with spurting hemorrhage, taking into account several limitations: deep ulcers bearing gross vessels, and lack of cooperation by the patient. Prophylactic treatment of the bleeding ulcer with a visible non-spurting vessel may be indicated whenever we make a proper selection of the patients with a greater possibility of hemorrhagic recurrence. | 10.1055/s-2007-1018234 |
pubmed_1005_24324 | In studies on temporal order perception, immediate as well as sustained effects of multisensory integration have been demonstrated repeatedly. Regarding duration perception, the corresponding literature reports clear immediate effects of multisensory integration, but evidence on sustained effects of multisensory duration integration is scarce. In fact, a single study [Heron, J. et al. (2013). A neural hierarchy for illusions of time: Duration adaptation precedes multisensory integration, J. Vis. 13, 1-12.] investigated adaptation to multisensory conflicting intervals, and found no sustained effects of the audiovisual conflict on perceived duration of subsequently presented unimodal visual intervals. In two experiments, we provide independent evidence in support of this finding. In Experiment 1, we demonstrate that adaptation to audiovisual conflict does not alter perceived duration of subsequently presented visual test intervals. Thus, replicating the results of Heron et al. (2013), we observed no sustained effect of multisensory duration integration. However, one might argue that the prolonged exposure to consistent multisensory conflict might have prevented or hampered multisensory integration per se. In Experiment 2, we rule out this alternative explanation by showing that multisensory integration of audiovisual conflicting intervals is still effective after exposure to audiovisual conflict. This further strengthens the conclusion that multisensory integration of interval duration affects perception in an immediate, but not in a sustained manner. | 10.1163/22134808-18001296 |
pubmed_355_9314 | The sequence of the mitochondrial control region was determined in all 10 extant species commonly assigned to the suborder Mysticeti (baleen or whalebone whales) and to two odontocete (toothed whale) species (the sperm and the pygmy sperm whale). In the mysticetes, both the length and the sequence of the control region were very similar, with differences occurring primarily in the first approximately 160 bp of the 5' end of the L-strand of the region. There were marked differences between the mysticete and sperm whale sequences and also between the two sperm whales. The control region, less its variable portion, was used in a comparison including the 10 mysticete sequences plus the same region of an Antarctic minke whale specimen and the two sperm whales. The difference between the minke whales from the North Atlantic and the Antarctic was greater than that between any acknowledged species belonging to the same genus (Balaenoptera). The difference was similar to that between the families Balaenopteridae (rorquals) and Eschrichtiidae (gray whales). The findings suggest that the Antarctic minke whale should have a full species status, B. bonaerensis. Parsimony analysis separated the bowhead and the right whale (family Balaenidae) from all remaining mysticetes, including the pygmy right whale. The pygmy right whale is usually included in family Balaenidae. The analysis revealed a close relationship between the gray whale (family Eschrichtiidae) sequence and those of the rorquals (family Balaenopteridae). The gray whale was included in a clade together with the sei, Bryde's, fin, blue, and humpback whales. This clade was separated from the two minke whale types, which branched together. | 10.1093/oxfordjournals.molbev.a040061 |
pubmed_263_16202 | BACKGROUND
Treatment guidelines state that all patients with bipolar disorder should use pharmacological prophylaxis; however the actual use of prophylactic drugs after bipolar disorder diagnosis is unknown. Our aim was to assess the use of, and predictors for, pharmacoprophylaxis in newly diagnosed bipolar disorder patients.
METHODS
Data from three Swedish nationwide registers were obtained. We identified patients aged 18-75 with a first time diagnosis of bipolar disorder between 2006 and 2012 (n=31,770) and reviewed subsequent mood-stabilizer and antipsychotic prescription fills. In multivariable Cox regression models, we studied demographic and illness related factors as predictors of prescription fills after diagnosis.
RESULTS
In total, 72.2% (95% confidence interval [CI] 71.7-72.7%) of the patients filled a prescription of a prophylactic drug within 3 months after diagnosis. Pharmacological prophylaxis was mainly associated with a longer duration of hospitalization at bipolar disorder diagnosis (adjusted hazard ratio [AHR] 2.18; CI 2.02-2.35 for a hospitalization of ≥28 days compared to <7 days) and previous use of any mood-stabilizer or antipsychotic (inpatients: AHR 1.24; CI 1.17-1.31 and outpatients: AHR 1.78; CI 1.73-1.84).
LIMITATIONS
We had no information on drug prescriptions that were never filled.
CONCLUSIONS
The proportion of newly diagnosed bipolar disorder patients without pharmacological prophylaxis is substantial. Patients who are naïve to mood-stabilizers and antipsychotics and are hospitalized for a brief period at diagnosis are the ones least likely to initiate pharmacoprophylaxis, suggesting that this group deserves attention in order to improve the long term prognosis. | pubmed_263_16202 |
pubmed_933_5211 | We have demonstrated efficient conversion of ultrashort-pulse laser energy to x rays with energies above 1 keV, using laser-produced plasmas generated on a variety of microstructured surfaces. Lithographically produced grating targets generated 0.1 mJ of kilo-electron-volt x rays, and porous gold and aluminum targets emitted 1 mJ. This represents an improvement of a factor of 100 over flat targets. The K-shell emission spectrum of porous aluminum was composed primarily of heliumlike spectral lines. | 10.1364/ol.19.000484 |
pubmed_179_14030 | Nanoemulsions are considered as the most promising solution to improve the delivery of ophthalmic drugs. The design of ophthalmic nanoemulsions requires an extensive understanding of pharmaceutical as well as technological aspects related to the selection of excipients and formulation processes. This Review aims at providing the readers with a comprehensive summary of possible compositions of nanoemulsions, methods for their formulation (both laboratory and industrial), and differences between technological approaches, along with an extensive outline of the research methods enabling the confirmation of in vitro properties, pharmaceutical performance, and biological activity of the obtained product. The composition of the formulation has a major influence on the properties of the final product obtained with low-energy emulsification methods. Increasing interest in high-energy emulsification methods is a consequence of their scalability important from the industrial perspective. Considering the high-energy emulsification methods, both the composition and conditions of the process (e.g., device power level, pressure, temperature, homogenization time, or number of cycles) are important for the properties and stability of nanoemulsions. It is advisible to determine the effect of each parameter on the quality of the product to establish the optimal process parameters' range which, in turn, results in a more reproducible and efficient production. | 10.1021/acs.molpharmaceut.1c00650 |
pubmed_743_6073 | (1) Background: Young infants have a high risk of serious infection. The Systematic Inflammatory Response Syndrome (SIRS) criteria can be useful to identify both serious bacterial and viral infections. The aims of this study were to evaluate the diagnostic performance of the SIRS criteria for identifying serious infections in febrile young infants and to identify potential clinical predictors of such infections. (2) Methods: We conducted this prospective cohort study including febrile young infants (aged < 90 days) seen at the emergency department with a body temperature of 38.0 °C or higher. We calculated the diagnostic performance parameters and conducted the logistic regression analysis to identify the predictors of serious infection. (3) Results: Of 311 enrolled patients, 36.7% (n = 114) met the SIRS criteria and 28.6% (n = 89) had a serious infection. The sensitivity, specificity, positive predictive value, and positive likelihood ratio of the SIRS criteria for serious infection was 45.9%, 69.4%, 43.5%, 71.4%, 1.5, and 0.8, respectively. Logistic regression showed that male gender, body temperature ≥ 38.5 °C, heart rate ≥ 178 bpm, and age ≤ 50 days were significant predictors. (4) Conclusions: The performance of the SIRS criteria for predicting serious infections among febrile young infants was poor. | 10.3390/children8111003 |
pubmed_288_14223 | Immunostimulatory therapy is a promising approach to improving the treatment of systemic fungal infections such as paracoccidioidomycosis (PCM), whose drug therapy is usually prolonged and associated with toxic side effects and relapses. The current study was undertaken to determine if the injection of a T helper (Th) 1-stimulating adjuvant in P. brasiliensis-infected mice could have a beneficial effect on the course of experimental PCM. For this purpose, mice were infected and treated with complete Freund's adjuvant (CFA), a well-established Th1 experimental inductor, or incomplete Freund's adjuvant (IFA - control group) on day 20 postinfection. Four weeks after treatment, the CFA-treated mice presented a mild infection in the lungs characterized by absence of epithelioid cell granulomas and yeast cells, whereas the control mice presented multiple sites of focal epithelioid granulomas with lymphomonocytic halos circumscribing a high number of viable and nonviable yeast cells. In addition, CFA administration induced a 2.4 log reduction (>99%) in the fungal burden when compared to the control group, and led to an improvement of immune response, reversing the immunosuppression observed in the control group. The immunotherapy with Th1-inducing adjuvant, approved to be used in humans, might be a valuable tool in the treatment of PCM and potentially useful to improve the clinical cure rate in humans. | 10.1371/journal.pntd.0000183 |
pubmed_597_744 | Nonphotosynthetic plants possess strongly reconfigured plastomes attributable to convergent losses of photosynthesis and housekeeping genes, making them excellent systems for studying genome evolution under relaxed selective pressures. We report the complete plastomes of 10 photosynthetic and nonphotosynthetic parasites plus their nonparasitic sister from the broomrape family (Orobanchaceae). By reconstructing the history of gene losses and genome reconfigurations, we find that the establishment of obligate parasitism triggers the relaxation of selective constraints. Partly because of independent losses of one inverted repeat region, Orobanchaceae plastomes vary 3.5-fold in size, with 45 kb in American squawroot (Conopholis americana) representing the smallest plastome reported from land plants. Of the 42 to 74 retained unique genes, only 16 protein genes, 15 tRNAs, and four rRNAs are commonly found. Several holoparasites retain ATP synthase genes with intact open reading frames, suggesting a prolonged function in these plants. The loss of photosynthesis alters the chromosomal architecture in that recombinogenic factors accumulate, fostering large-scale chromosomal rearrangements as functional reduction proceeds. The retention of DNA fragments is strongly influenced by both their proximity to genes under selection and the co-occurrence with those in operons, indicating complex constraints beyond gene function that determine the evolutionary survival time of plastid regions in nonphotosynthetic plants. | 10.1105/tpc.113.113373 |
pubmed_400_1019 | Adult bone marrow is a rich reservoir of hematopoietic and vascular stem and progenitor cells. Mobilization and recruitment of these cells are essential for tissue revascularization. Physiological stress, secondary to tissue injury or tumor growth, results in the release of angiogenic factors, including vascular endothelial growth factor (VEGF), which promotes mobilization of stem cells to the circulation, contributing to the formation of functional vasculature. VEGF interacts with its receptors, VEGFR2 and VEGFR1, expressed on endothelial and hematopoietic stem cells, and thereby promotes recruitment of these cells to neo-angiogenic sites, accelerating the revascularization process. The mobilization of stem cells from marrow is a dynamic process, regulated by shear stress imparted by blood flow, and the activation of metalloproteinases that induce the release of 'Kit ligand', facilitating egress from the marrow to the circulation. Identification of the molecular pathways that support the proliferation and differentiation of vascular stem and progenitor cells will open up new avenues for the design of clinical trials to accelerate tissue vascularization and organogenesis. | 10.1016/s1471-4914(03)00021-2 |
pubmed_288_21461 | We describe a case of brainstem inflammation in a young man which at first defied diagnosis. However, after his death, and notwithstanding our inability to find a cause at autopsy, we did not give up. After sending paraffin blocks to the Centers for Disease Control in Atlanta, Georgia, USA, they suggested the diagnosis of Balamuthia (amoebic) infection. | 10.1136/jnnp.2007.142547 |
pubmed_219_16998 | Oocyte vitrification is a preservation fertility strategy, which can be performed in women after puberty to preserve gametes before beginning a gonadotoxic anticancer treatment. Based on available literature and our personal data, we aim to provide an overview about the feasibility, the clinical and logistic difficulties of oocyte vitrification in the field of oncofertility: limit age for oocyte cryopreservation, time required and protocols for ovarian controlled stimulation, ovarian response to stimulation, for what hopes of pregnancy? | pubmed_219_16998 |
pubmed_1018_19899 | Delirium is a serious health problem with significant negative consequences which is experienced by many hospitalized elderly patients. Because of its clinical impact and potential reversibility, prompt treatment of delirium is essential. Therefore an understanding of delirium, its manifestations, methods of detection, prevention, and treatment in hospitalized elderly patients is needed. This article provides an overview of the diagnostic and therapeutic dilemmas of delirium. | pubmed_1018_19899 |
pubmed_1010_4196 | OBJECTIVES
The objective of this study was to compare the results of two methods for sparing the pronator quadratus in volar plating of distal radius fractures.
METHODS
A total of 110 patients were randomized to volar plating with sparing of the pronator quadratus either by a transverse incision along the distal border of the pronator quadratus (Group A, 55 people) or by the brachioradialis splitting method (Group B, 55 people). The operative and radiation time, range of motion, grip strength, Disabilities of the Arm, Shoulder, and Hand (DASH) scores, Visual Analog Scale (VAS) scores, and complications were recorded.
RESULTS
There were no significant differences in the mean operative time, radiation time, mean bone union time, or total complication rate between the groups. We found no significant differences in range of motion, grip strength, VAS scores, and DASH scores at any of the study intervals between the groups. Although neurapraxia of the superficial branch of the radial nerve was more common in Group B than in Group A (6.7% vs. 0%), the difference was not significant.
CONCLUSIONS
Both methods were efficient approaches for sparing the pronator quadratus and had similar clinical outcomes, but they had different indications. | 10.1177/0300060519893851 |
pubmed_227_5926 | BACKGROUND
: House dust mite (HDM) allergen is one of the most common allergens to which asthma patients are sensitised. Prevalence of HDM allergy varies in the literature. Use of HDM-impermeable bed covers reduces exposure to HDM allergen. The aim of this study was to assess the prevalence of HDM allergy in a primary care population of asthma patients, as well as the use of HDM-impermeable bed covers by these patients.
METHODS
: A random sample of asthma patients between 16 and 60 years old was taken from general practices. Allergy was assessed with a radio allegro sorbent test (RAST). A questionnaire was used to identify demographic characteristics and the actual use of bed covers.
RESULTS
: 534 patients were invited and 160 patients participated. 53 patients not willing to participate were randomly selected to test the external validity of our findings. The sample was representative for the primary care asthma population. 48.8% of the asthma population was sensitised to HDM allergen. 25.6% of the HDM-allergic asthma patients were using HDM-impermeable bed covers.
CONCLUSION
: Almost half of the patients with asthma were sensitised to HDM allergen. Only a minority of the patients used HDM-impermeable bed covers. | 10.1016/j.pcrj.2005.04.005 |
pubmed_317_14369 | Mitogen-activated protein kinase (MAPK) signaling pathways play an essential role in the transduction of environmental stimuli to the nucleus, thereby regulating a variety of cellular processes, including cell proliferation, differentiation and programmed cell death. The components of the MAPK extracellular activated protein kinase (ERK) cascade represent attractive targets for cancer therapy as their aberrant activation is a frequent event among highly prevalent human cancers. MAPK networks are a model for computational simulation, mostly using ordinary and partial differential equations. Key results showed that these networks can have switch-like behavior, bistability and oscillations. In this work, we consider three representative ERK networks, one with a negative feedback loop, which present a binomial steady state ideal under mass-action kinetics. We therefore apply the theoretical result present in to find a set of rate constants that allow two significantly different stable steady states in the same stoichiometric compatibility class for each network. Our approach makes it possible to study certain aspects of the system, such as multistationarity, without relying on simulation, since we do not assume a priori any constant but the topology of the network. As the performed analysis is general it could be applied to many other important biochemical networks. | pubmed_317_14369 |
pubmed_192_4894 | In this paper a numerical study is presented that concentrates on the influence of the interface roughness that develops during plastic deformation of a metal, on the work of adhesion and on the change of interface energy upon contact with a glassy polymer. The polymer coating is described with a constitutive law that mimics the behavior of Poly-Ethylene Terephthalate. It includes an elastic part, a yield stress, softening and hardening with increasing strains. For the interface between the metal and the polymer a mixed-mode (mode I and II) stress-separation law is applied that defines the interface energy and an interaction length scale. At the onset of deformation the surface of the substrate has a self-affine roughness characterized by the so-called Hurst exponent, a correlation length and an rms roughness amplitude, that evolves as a function of increasing strain. The findings are the following: the interface energy decreases until the strain at yield of the polymer coating. Interestingly, after yielding as the polymer starts to soften macroscopically, the decreasing average stress levels result in partial recovery of the interface energy at the interface. At higher strains, when macroscopic hardening develops the recovery of the interface stops and the interface energy decreases. The effect of coating thickness is discussed as well as the physical relevance of various model parameters. | 10.1007/s10853-006-1374-z |
pubmed_723_11415 | BACKGROUND
The information concerning non-invasive, easily obtainable, and accurate biomarkers for diagnosis of lupus nephritis (LN) is extremely limited. The aim of this study was to evaluate the diagnostic performance of cystatin C (CysC) and complement component 1q (C1q) for LN.
METHODS
A case-control study that included 905 patients with systemic lupus erythematosus (SLE) without LN (group SLE), 334 patients with active lupus nephritis (group LNA), 255 patients with inactive lupus nephritis (group LNI), and 497 healthy individuals (group HC) was performed in Mianyang Central Hospital from March 2017 to December 2018. The serum levels of CysC, C1q, urea (Urea), and creatinine (Creat) were measured, and 2 estimated glomerular filtration rates (eGFRCysC and eGFRCreat) were calculated by equations which were based on serum CysC established by our group and the modification of diet in renal disease (MDRD), respectively. ANOVA analysis or Kruskal-Wallis test was used for comparing the differences among the groups, and receiver operating characteristic (ROC) curve was applied to identify the diagnostic efficiencies of individual or combined multiple indicators.
RESULTS
Significantly elevated CysC and decreased C1q were observed in the LNA and LNI groups, which was in contrast to their levels in the SLE and HC groups. CysC (AUC = 0.906) or eGFRCysC (AUC = 0.907) assessed the highest diagnostic performance on LNA when detected individually, followed by C1q (AUC = 0.753). Joint utilization of C1q and CysC achieved very good performance (AUC = 0.933) which approximated to the best one observed in the combinations of C1q, Urea, CysC, eGFRCreat, and Creat (AUC = 0.975).
CONCLUSION
The separately detected CysC (eGFRCysC) and C1q were superior to the conventional biomarkers Urea, Creat, and eGFRCreat in the diagnosis of LNA. Moreover, although the combined detection of Urea, Creat, C1q, CysC, and eGFRCreat had the greatest diagnostic performance, the joint utilization of CysC and C1q could be prioritized for rapid discrimination of LNA if the economic burden is taken into consideration. | 10.1186/s13075-019-2065-x |
pubmed_613_1381 | The asymmetric unit of the title compound, 2C(8)H(6)N(2)·C(6)H(7)NO·2H(2)O, contains two quinoxaline mol-ecules, one mol-ecule of 3-amino-phenol and two water mol-ecules which are hydrogen bonded to form a two-dimensional polymeric structure. Each of the symmetry-independent quinoxaline mol-ecules forms separate stacks of different symmetry. In one set of stacks, the mol-ecules are related by a screw axis and are slightly tilted [dihedral angle = 7.12 (1)°]. In the second set of stacks, adjacent mol-ecules are parallel and related by an inversion center [inter-planar distances = 3.376 (4) and 3.473 (4) Å]. | 10.1107/S1600536808010568 |
pubmed_306_1016 | The effect of eccentricity distortions of core-multishell quantum wires on their electron, hole and exciton states is theoretically investigated. Within the effective mass approximation, the Schrödinger equation is numerically solved for electrons and holes in systems with single and double radial heterostructures, and the exciton binding energy is calculated by means of a variational approach. We show that the energy spectrum of a core-multishell heterostructure with eccentricity distortions, as well as its magnetic field dependence, are very sensitive to the direction of an externally applied electric field, an effect that can be used to identify the eccentricity of the system. For a double heterostructure, the eccentricities of the inner and outer shells play an important role on the excitonic binding energy, especially in the presence of external magnetic fields, and lead to drastic modifications in the oscillator strength. | 10.1088/0953-8984/25/48/485501 |
pubmed_89_24976 | BACKGROUND
The main goal of the study was to investigate the effects of a short loving-kindness meditation (LKM) on explicit and implicit evaluations of oneself and disliked public persons. We expected a more positive explicit and implicit evaluation of oneself and a disliked public person after the LKM and a mood improvement.
METHODS
Before and after the implementation of a short LKM vs. imagery task, mood, explicit and implicit evaluations were analyzed in 69 students.
RESULTS
Our results demonstrated only a reduction in negative and positive mood in both groups and regarding the explicit and implicit tasks, only a significant main effect of picture and a trend for the time*group interaction for mood, implicit and explicit attitudes with medium effect-sizes.
CONCLUSIONS
A possible influence of a short intervention on emotional evaluations should be treated with caution. The claim that a short loving-kindness meditation enhances social connectedness might awake false hopes. This study suggests being careful with the interpretation of single meditation effects and future studies should examine the effects of a long-lasting meditation training on explicit and implicit evaluations of the self and disliked politicians as well as the sustainability of those effects. | 10.1186/s40359-022-00817-5 |
pubmed_99_5371 | There is much evidence to suggest that temporal arteritis and rhizomelic polymyalgia are both immunological diseases. The classic results of experimental pathology are discussed, together with the relations between rhizomelic polymyalgia and both virus hepatitis B and the HLA system. From the clinical standpoint, it is now agreed that differences in individual response may lead to either a synovial or an arteritic response in both forms. Their association in what Hamrin has called "polymyalgia arteritica" is also common. | pubmed_99_5371 |
pubmed_585_18543 | PURPOSE
To evaluate the interobserver and intraobserver reliability of radiographic assessment of tunnel placement in anterior cruciate ligament reconstruction.
METHODS
Seven sports fellowship-trained orthopaedic surgeons in the Multicenter Orthopaedic Outcomes Network (MOON) group participated in the study. We prospectively enrolled 54 consecutive patients after primary anterior cruciate ligament reconstruction. Postoperative plain radiographs were obtained including a full-extension anteroposterior view of the knee, a lateral view of the knee in full extension, and a notch view at 45° of flexion (Rosenberg view). Three blinded reviewers performed 8 different radiographic measurements including those of Harner and Aglietti/Jonsson. Intraclass correlation coefficients were used to determine reliability of the measurements. Intrarater reliability was assessed by repeated measurements of a subset of 20 patient images from 1 institution, and inter-rater reliability was assessed by use of all 54 sets of films from a total of 4 institutions.
RESULTS
Intraobserver reliability for femoral measures ranged from none to substantial, with notch height having the worst results. Intraobserver reliability was moderate to almost perfect for tibial measures. Interobserver reliability ranged from slight to moderate for femoral measures. The Harner method for determining tunnel depth was more reliable than the Aglietti/Jonsson method. Interobserver reliability for tibial measures ranged from fair to substantial. The presence of metal interference screws did not improve reliability of measurements.
CONCLUSIONS
Postoperative radiographs are easily obtained, but our results show that radiographic measurements are of quite variable reliability, with most of the results falling into the fair to moderate categories. | 10.1016/j.arthro.2011.12.010 |
pubmed_708_16083 | The four closely related genes encoding eggshell proteins in the human parasite Schistosoma japonicum are described. A cDNA and a genomic DNA library were constructed and members of the eggshell protein gene family isolated. The four genes in this family do not contain introns, and differ in organization and nucleotide sequence from the related set of genes in Schistosoma mansoni and Schistosoma haematobium. The coding sequences of two of the S. japonicum genes and their flanking regions were determined. Transcription start sites for these genes were shown by primer extension analysis to occur 47 and 50 nucleotides in front of the start codon. A female-specific component in nuclear extracts binds to a DNA fragment containing conserved sequences upstream of the transcription start sites. The deduced protein sequences of 207 and 212 amino acids are composed of 50% glycine with continuous glycine regions as long as 11 residues. In vitro translations of male and female RNAs revealed female-specific translation products, the sizes of which were consistent with the eggshell proteins. | 10.1016/0166-6851(90)90114-2 |
pubmed_263_19873 | The type 2 iodothyronine deiodinase (D2) is essential for feedback regulation of TSH by T4. We genetically inactivated in vivo D2 in thyrotrophs using a mouse model of Cga-driven cre recombinase. Pituitary D2 activity was reduced 90% in the Cga-cre D2 knockout (KO) mice compared with control Dio2(fl/fl) mice. There was no growth or reproductive phenotype. Basal TSH levels were increased 1.5- to 1.8-fold, but serum T4 and T3 were not different from the controls in adult mice. In hypothyroid adult mice, suppression of TSH by T4, but not T3, was impaired. Despite mild basal TSH elevation, the TSH increase in response to hypothyroidism was 4-fold reduced in the Cga-cre D2KO compared with control mice despite an identical level of pituitary TSH α- and β-subunit mRNAs. In neonatal Cga-cre D2KO mice, TSH was also 2-fold higher than in the controls, but serum T4 was elevated. Despite a constant TSH, serum T4 increased 2-3-fold between postnatal day (P) 5 and P15 in both genotypes. The pituitary, but not cerebrocortical, D2 activity was markedly elevated in P5 mice decreasing towards adult levels by P17. In conclusion, a congenital severe reduction of thyrotroph D2 causes a major impairment of the TSH response to hypothyroidism. This would be deleterious to the compensatory adaptation of the thyroid gland to iodine deficiency. | 10.1210/en.2014-1698 |
pubmed_298_9955 | Based on high-resolution SPOT-5 images, combined with topographic (1:10000) calculating terrain-bit index, the distribution characteristics of woodlands in different terrain niches, and the buffer radii of different roads, water bodies and settlements were identified by using ArcGIS space overlay and buffer analysis function. Results showed that woodland resources were abundant, and arbor woodland and shrub land were the main species, which mainly distributed in two mountain areas (Fangdou Mountain, Qiyao Mountain) affected by topographic restriction and woodland natural basis. The woodland terrain niche distribution index showed an overall upward trend with increasing terrain niche gradient, especially for the arbor woodland and shrub land, while the other woodland types presented an opposite trend. The percentage of woodland area occupying the corresponding buffer radius around the roads, waterbodies and settlements had a strong similarity with the woodland terrain niche distribution index. Only around the settlements, bamboo forest, sparse woodland and immature woodland occupied higher percentages of the woodland area of the corresponding buffer radius than that of arbor woodland and shrub land. Woodland distribution was mainly controlled by large landform patterns of mountain features, while the distribution of woodlands in the different terrain niches and the different buffer radii of roads, waterbodies and settlements were driven mainly by duress of human activities under the auspices of the large landform patterns. | pubmed_298_9955 |
pubmed_82_21400 | HYPOTHESIS
This study aimed to compare reaction times (RTs) to auditory stimuli of two groups of normal-hearing subjects differing only in terms of tinnitus sensation.
BACKGROUND
The RTs to auditory stimuli as a psychophysical measurement for threshold and suprathreshold hearing are said to provide a behavioral clue to some aspects of neural processing in the auditory system.
METHODS
To explore how patients with tinnitus perceive the intensity of threshold and suprathreshold sound stimuli, RTs were obtained from normal-hearing subjects with tinnitus (experimental group, N=15) and from normal-hearing subjects without tinnitus (control group, N=15) by means of exposure to two different sets of frequencies: the tinnitus frequencies and the nontinnitus frequency of 1,000 Hz.
RESULTS
There were significant differences in RTs in the experimental group and in the control group not only for the tinnitus frequencies, but also for the nontinnitus frequency of 1,000 Hz. The experimental group had shorter RTs than did the control group at sensation levels (SLs) near the threshold, with no significant differences between groups at sound stimuli in the suprathreshold intensity range.
CONCLUSIONS
It is assumed that the above-mentioned reduction in RTs shows a dysfunction of cochlear mechanisms contributing to tinnitus. Conversely, tinnitus also can be considered as an additional auditory input leading to shorter RTs at SLs near the threshold. The current study suggests that the reaction time procedure to auditory stimuli offers complementary information on tinnitus sensation and might be a valuable method in demonstrating general differences and tendencies that have been neglected so far. Analysis for the mechanisms of tinnitus sensation allows for the possibility of facilitating the process of tinnitus habituation and, ultimately, the relief from it. | pubmed_82_21400 |
pubmed_584_22671 | Inflammatory disorders such as rheumatoid arthritis (RA), may have profound effects on skeletal homeostasis. In contrast to physiologic remodeling in which mechanical influences and/or systemic endocrine hormones initiate the remodeling process, in disorders such as RA the recruitment of macrophage lineage cells to sites of inflammation and the action of local osteoclastogenic cytokines associated with the inflammatory process initiate the remodeling process. In both physiologic and pathologic remodeling, osteoclasts appear to be the principal cell type responsible for the bone resorption. In addition, many of the same cytokines and mediators are involved in physiologic and pathologic bone remodeling. These observations have important implications with respect to the development of therapeutic strategies to prevent bone loss in inflammatory conditions. | 10.1007/s00223-002-1049-y |
pubmed_19_8858 | PURPOSE
A mild allergic reaction assumed to be caused by injection of Tc-99m sestamibi for a stress myocardial perfusion imaging (MPI) is presented. We want to discuss the risk involved in completing the MPI with another sestamibi injection, and the precautions and possible treatment in case of a further reaction.
MATERIAL AND METHODS
A patient experienced a maculo-papular exanthema, i.e. a mild, probably allergic, adverse event (AE) after a stress MPI including administration of a dose of Tc-99m sestamibi. A rest MPI was needed to decide whether coronary bypass surgery should be performed. After prophylactic treatment with antihistamine and corticosteroid, an uneventful rest MPI was performed.
DISCUSSION AND CONCLUSION
International recommendations or guidelines related to treatment of AEs after nuclear medicine studies do not exist. Serious AEs in nuclear medicine are very rare, but anaphylactic reactions have been reported and may be life threatening. If repeated administration of the radio-pharmaceutical must be given, the prophylactic and therapeutic interventions should follow general international guidelines for allergic reactions. | 10.1111/j.1475-097X.2011.01008.x |
pubmed_875_6066 | INTRO
Although the use of laparoscopy has significantly increased in colorectal procedures, robotic surgery may enable additional cases to be performed using a minimally invasive approach. We separately evaluated the value of laparoscopic and robotic colorectal procedures compared to the open approach.
METHODS
Patients undergoing nonemergent colorectal operations from 2010 to 2013 with National Surgical Quality Improvement Project data were identified. Robotic and laparoscopic procedures were separately matched (1:1) to open cases. Outcomes included 30-day composite morbidity, length of stay, operative time, and inpatient costs. Frequently used intraoperative disposable items were categorized, and significant cost contributors were identified by surgical approach. Statistical differences were determined with Chi-square and Wilcoxon signed-rank tests.
RESULTS
Both laparoscopic (n = 67) and robotic (n = 45) approaches were associated with decreased composite morbidity compared to matched open cases (lap vs. open: 22.4% vs. 49.2%, P < .01; robotic vs. open: 6.7% vs. 33.3%, P < .01). Median length of stay was significantly shorter for both laparoscopic and robotic compared to open surgery (lap vs. open: 5 vs. 7 days, P < .01; robotic vs. open: 5 vs. 7 days, P < .01). Median hospital costs were similar between laparoscopic and open surgery ($13,319 vs. $14,039; P = .80) and robotic and open surgery ($13,778 vs. $13,629; P = .48).
CONCLUSION
These findings illustrate the value for both laparoscopic and robotic approaches to colorectal surgery compared to the open approach in terms of short-term outcomes and inpatient costs. Advanced intraoperative disposable items such as cutting staplers and energy devices are important targets for additional cost containment. | 10.1089/lap.2015.0620 |
pubmed_1121_20421 | This paper describes a new unsupervised machine-learning method for simultaneous phoneme and word discovery from multiple speakers. Phoneme and word discovery from multiple speakers is a more challenging problem than that from one speaker, because the speech signals from different speakers exhibit different acoustic features. The existing method, a nonparametric Bayesian double articulation analyzer (NPB-DAA) with deep sparse autoencoder (DSAE) only performed phoneme and word discovery from a single speaker. Extending NPB-DAA with DSAE to a multi-speaker scenario is, therefore, the research problem of this paper.This paper proposes the employment of a DSAE with parametric bias in the hidden layer (DSAE-PBHL) as a feature extractor for unsupervised phoneme and word discovery. DSAE-PBHL is designed to subtract speaker-dependent acoustic features and speaker-independent features by introducing parametric bias input to the DSAE hidden layer. An experiment demonstrated that DSAE-PBHL could subtract distributed representations of acoustic signals, enabling extraction based on the types of phonemes rather than the speakers. Another experiment demonstrated that a combination of NPB-DAA and DSAE-PBHL outperformed other available methods accomplishing phoneme and word discovery tasks involving speech signals with Japanese vowel sequences from multiple speakers. | 10.3389/frobt.2019.00092 |
pubmed_52_3517 | OBJECTIVES
The particular purpose of our study was to assess the impact of environmental tobacco smoke (ETS) on the individual variability of blood lead levels in pregnant women as earlier publications demonstrated the increased blood lead in smokers.
MATERIALS AND METHODS
The material consisted of 240 pregnant women who participated in a prospective cohort study on vulnerability of the fetus and infant to environmental hazards. The enrolment included only non-smoking women with singleton pregnancies between the ages of 18-35 years. Whole blood lead concentrations were determined using inductively coupled plasma mass spectrometry.
RESULTS
On average, blood-lead measured in pregnant women at delivery was low (GM = 1.7 microg/dL; 95% CI:1.6-1.8 microg/dL) and none of them showed levels above 4.0 microg/dL, but persons reporting exposure to ETS had significantly higher blood lead level (GM = 1.9 microg/dL; 95%CI:1.8-2.1 microg/dL) than those free from this exposure (GM = 1.6 microg/dL; 95%CI:1.5-1.7 microg/dL). In order to single out the effect of the ETS exposure from the confounding variables, we used the stepwise multivariate linear regression for log blood-lead in maternal blood as dependent variable and a set of independent variables, such as age, weight of women before pregnancy and their education level. The results of the analysis showed that all the independent variables included in the model explained 11% of total blood-lead variability among the study women. The strongest component of variance was attributed to ETS exposure (5%), age (3%), education level (2%) and weight (1%). Inclusion into the model of other variables, e.g., residence area and traffic intensity did not improve the proportion of explained variability.
CONCLUSIONS
The reason for higher levels of blood-lead in the ETS-exposed women may result from the fact that tobacco smoke contains lead. However, it is possible that inhaled tobacco smoke also increases the absorption of lead from particulate matter deposited in the bronchial tree. | 10.2478/v10001-006-0034-5 |
pubmed_631_15182 | While anti-TNF agents have had a marked impact in the treatment of inflammatory bowel disease, a significant number of patients lose their response to these medications over time. Clinical trials have demonstrated that antibodies against anti-TNF medications may impact treatment response and increase the risk of infusion reaction. Scheduled dosing and concurrent use of immunomodulators may help to mitigate these risks via inhibiting the formation of these antibodies. The recent availability of assays to measure anti-TNF drug levels and antibodies against anti-TNFs offer the opportunity to assess patients who have lost response with infliximab and adalimumab, and potentially determine the most appropriate therapeutic strategy. There is growing evidence that such testing improves patient outcomes and is cost-effective, although heterogeneity in the assays used in clinical and observational trials has resulted in mixed results. | 10.1007/s11938-013-0004-5 |
pubmed_531_11931 | Purification procedures that appear to be generally applicable to invertebrate MTs have only recently been developed and are described here. Thus far, few invertebrate MTs have been purified and characterized, although proteins that exhibit similarities to MT have been identified in numerous invertebrate species. A greater understanding of MTs of this group, which comprises most of the animals in the animal kingdom, will provide the basis for increased understanding of the evolution of this ubiquitous protein. Additionally, specific invertebrate species may provide useful models for probing MT function and contribute to a greater understanding of the biological role of MT. | 10.1016/0076-6879(91)05106-6 |
pubmed_1072_17451 | Considering that chemotherapy resistance is vital to the progression of cervical carcinoma, emerging researchers are focused on developing anti-tumor drugs to assist the treatment efficiency of chemotherapy. Melatonin has anti-tumor activity via several mechanisms including its anti-proliferative and pro-apoptotic effects as well as its potent pro-oxidant action in tumor cells. Therefore, melatonin may be useful for the treatment of tumors in association with chemotherapy drugs. Here, we studied the effect and mechanism of melatonin on HeLa cells apoptosis under cisplatin (CIS) treatment, particularly focusing on the caspase-9-related apoptosis pathway and mitophagy-mediated anti-apoptotic mechanism. The result indicated that co-stimulation of HeLa cells with CIS in the presence of melatonin further increased cellular apoptosis. Furthermore, concomitant treatments with melatonin and CIS significantly enhanced the mitochondrial structure and function damage, substantially augmented the caspase-9-dependent mitochondrial apoptosis with evidenced by lower mitochondria membrane potential, higher mitochondria ROS, and more pro-apoptotic proteins compared to the treatment with CIS alone. Mechanistically, melatonin inactivated mitophagy via blockade of JNK/Parkin, leading to the inhibition of anti-apoptotic mitophagy. The mitophagy had the ability to clear and remove damaged mitochondria, impairing CIS-mediated mitochondrial apoptosis. Activation of JNK/Parkin could alleviate the lethal effect of melatonin on HeLa cells. In summary, this study confirmed that melatonin sensitizes human cervical cancer HeLa cells to CIS-induced apoptosis through inhibition of JNK/Parkin/mitophagy pathways. | 10.1007/s11626-017-0200-z |
pubmed_690_20587 | The mode of T-lymphoma cell death induced by cold shock was studied. The rewarming of cells at 37 degrees C following a brief period of cold (0 degrees C) resulted in internucleosomal DNA fragmentation. The cells underwent cold shock-mediated apoptosis only at a reduced (2%) serum concentration. The apoptosis was not blocked by macromolecular synthesis inhibitors such as cycloheximide and antinomycin D, or by Quin-2. EGTA per se was responsible for the initiation of cell death. Colchicine also induced internucleosomal fragmentation of DNA. Our findings suggest that cold shock induced apoptosis is associated with low temperature mediated disruption of microtubules. The role of Ca2+ and growth factors in cold shock induced cell death is discussed. | pubmed_690_20587 |
pubmed_290_5568 | Electrolytic water technology is promising for sustainable energy utilization, but the lack of efficient electrocatalysts retards its application. The intrinsic activity of electrocatalysts is determined by its electronic structure, whereas the apparent activity can be further optimized by reasonable design on micro-/nanostructures of electrocatalysts. The core goal of electrocatalytic research is to reveal the relationship between the structure and performance of electrocatalysts, which is also the basis of reasonable design and construction of efficient electrocatalysts. Traditional synthetic methods, namely bottom-up and top-down routes, usually induce the change of different structural parameters at the same time. The solid-state conversion strategy, which is converts solid precursors into target materials through chemical reactions, has been widely adopted to produce materials with precisely controllable structures. In this Minireview, we focus on recent advances in the solid-state conversion synthesis of water-splitting electrocatalysts. First, the basis of solid-state conversion chemistry is introduced. Then, the specific methods of precise control of electronic structure by solid-state conversion and the relationship between electronic structure and performance are summarized. Based on the understanding of the electronic structure-performance relationship, synergistic regulation of electronic structure and micro-/nanostructures by solid-state conversion to achieve the copromotion of intrinsic activity and apparent activity are described. Finally, the remaining challenges in this field are discussed, and future research directions are proposed as well. | 10.1002/chem.201904021 |
pubmed_327_7496 | A novel splice site mutation (IVS7-1G-->A) in the T-protein gene (aminomethyltransferase, or AMT) of the glycine cleavage enzyme complex was found in a patient with nonketotic hyperglycinemia (NKH). A PCR/restriction enzyme method to detect this mutation was used to screen 100 NKH alleles and identified the mutation in three unrelated families. | 10.1002/1098-1004(2001)17:1<76::AID-HUMU17>3.0.CO;2-0 |
pubmed_475_10638 | About 15% of people in the world suffer migraine attacks. Migraine can induce a great impact in the quality of life, and the costs of medical care and loss of productivity can be also high. Non-steroidal anti-inflammatory drugs (NSAIDs) are the best treatment in mild-to-moderate migraine attacks and triptans are the first line option in the acute treatment of moderate-to-severe migraine attacks. At present, there are seven marketed triptans: sumatriptan, rizatriptan, zolmitriptan, eletriptan, naratriptan, almotriptan and frovatriptan. Obviously, every drug presents different pharmacokinetic and pharmacodynamics properties and, moreover, some triptans have several formulations. The prescription of one of these seven triptans for a specified patient is based in the drug profile: efficacy, safety, pharmacokinetics and pharmacodynamics. Other data to take account in the final prescription are clinical characteristics of the migraine attack (speed of onset, intensity of pain, lasting of the attack) and patient characteristics as working habits, life style or medical history. It is therefore mandatory to perform an individualization of the treatment of migraine attack. In recent years, several new patents of drugs have been registered in the treatment of migraine attack, although most of these are already known drugs that only provide new routes of administration. We present an update on the treatment of the migraine attack. | 10.2174/1574889809666140307115100 |
pubmed_286_8651 | Recently, we and others have found that hyperfiltration-associated increase in biomechanical forces, namely, tensile stress and fluid flow shear stress (FFSS), can directly and distinctly alter podocyte structure and function. The ultrafiltrate flow over the major processes and cell body generates FFSS to podocytes. Our previous work suggests that the cyclooxygenase-2 (COX-2)-PGE2-PGE2 receptor 2 (EP2) axis plays an important role in mechanoperception of FFSS in podocytes. To address mechanotransduction of the perceived stimulus through EP2, cultured podocytes were exposed to FFSS (2 dyn/cm2) for 2 h. Total RNA from cells at the end of FFSS treatment, 2-h post-FFSS, and 24-h post-FFSS was used for whole exon array analysis. Differentially regulated genes ( P < 0.01) were analyzed using bioinformatics tools Enrichr and Ingenuity Pathway Analysis to predict pathways/molecules. Candidate pathways were validated using Western blot analysis and then further confirmed to be resulting from a direct effect of PGE2 on podocytes. Results show that FFSS-induced mechanotransduction as well as exogenous PGE2 activate the Akt-GSK3β-β-catenin (Ser552) and MAPK/ERK but not the cAMP-PKA signal transduction cascades. These pathways are reportedly associated with FFSS-induced and EP2-mediated signaling in other epithelial cells as well. The current regimen for treating hyperfiltration-mediated injury largely depends on targeting the renin-angiotensin-aldosterone system. The present study identifies specific transduction mechanisms and provides novel information on the direct effect of FFSS on podocytes. These results suggest that targeting EP2-mediated signaling pathways holds therapeutic significance for delaying progression of chronic kidney disease secondary to hyperfiltration. | 10.1152/ajprenal.00325.2017 |
pubmed_1040_15705 | Long-term cultures of hepatocytes were established from livers of human fetuses obtained by abortion at 18 to 23 wk of gestation. Cells obtained by collagenase dissociation of liver were maintained in defined serum-free medium on a substratum of positively charged plastic. Under these conditions, the cells divide and form a confluent monolayer. After multiple passages over a period of 3 mo., the cells retained an epithelioid morphology and continued to synthesize and secrete albumin. | 10.1007/BF02620932 |
pubmed_349_15822 | Many biomedical and clinical studies with time-to-event outcomes involve competing risks data. These data are frequently subject to interval censoring. This means that the failure time is not precisely observed but is only known to lie between two observation times such as clinical visits in a cohort study. Not taking into account the interval censoring may result in biased estimation of the cause-specific cumulative incidence function, an important quantity in the competing risks framework, used for evaluating interventions in populations, for studying the prognosis of various diseases, and for prediction and implementation science purposes. In this work, we consider the class of semiparametric generalized odds rate transformation models in the context of sieve maximum likelihood estimation based on B-splines. This large class of models includes both the proportional odds and the proportional subdistribution hazard models (i.e., the Fine-Gray model) as special cases. The estimator for the regression parameter is shown to be consistent, asymptotically normal and semiparametrically efficient. Simulation studies suggest that the method performs well even with small sample sizes. As an illustration, we use the proposed method to analyze data from HIV-infected individuals obtained from a large cohort study in sub-Saharan Africa. We also provide the R function ciregic that implements the proposed method and present an illustrative example. Copyright © 2017 John Wiley & Sons, Ltd. | 10.1002/sim.7350 |
pubmed_570_10641 | This study attempts to determine the scale-dependent hierarchical spatial variation and longitudinal distributions of Sicyopterus japonicus year round. The distribution of S. japonicus in the Datuan Stream in northern Taiwan was surveyed during the fall and winter 2007, as well as the spring and summer of 2008. The spatial structure of S. japonicus density was modeled using geostatistics. The longitudinal distributions of S. japonicus density were then estimated using kriging and hydrology distance with nested variogram models. Variography results indicate that nested variogram models could reflect the hierarchical structure in the spatial variation of seasonal S. japonicus density, with the small, median, and large ranges representing three nested scales. Models for the four seasons were consistent in that they shared the same shape of variogram models with various ranges and sill values. This model shape consistency implies stationary spatial correlations in the longitudinal fish distribution across the four seasons. The Kriging geostatistical method based on the multiple scales nested variogram models also provided robust estimates of S. japonicus densities at unsampled sections. We conclude that S. japonicus densities exhibit hierarchical patterns and variation in the four seasons along the study stream. Geostatistical methods with a nested variograms and hydrological distance are a highly effective means of delineating the hierarchical structure in longitudinal patterns of S. japonicus density in each season, providing estimates of the S. japonicus density for hierarchically structured spatial distributions and expanding knowledge of S. japonicus beyond the limits imposed by spatial and temporal scales. | 10.1007/s10661-010-1666-2 |
pubmed_684_1973 | The utility of a piezoquartz immunosensor coated with lipopolysaccharides (LPS) for the quantification of antibody specificities was demonstrated. Immunochemical reactions were monitored according to the changes in the weight of sensor bioreceptor layer with high sensitivity (detection limit, 1.3 microg/ml) and assay rate (10 min) without any additional labels. The capabilities of this sensor were demonstrated by the example of quantifying the cross-reactivity of blood serum antibodies with the LPS of Yersinia enterocolitica serotypes O:3, O:5, O:5.27, O:6.30, and O:6.31. The proposed approach is promising for clinical diagnostics of yersiniosis, an infectious intestinal disease. | pubmed_684_1973 |
pubmed_347_6026 | Moving objects can cover large distances while they are processed by the eye, usually resulting in a spatially lagged retinal response. We identified a network of electrically coupled motion-coding neurons in mouse retina that act collectively to register the leading edges of moving objects at a nearly constant spatial location, regardless of their velocity. These results reveal a previously unknown neurophysiological substrate for lag normalization in the visual system. | 10.1038/nn.3308 |
pubmed_564_3334 | We report a case of cytomegalovirus infection of the seminal vesicle and ductus deferens in a 32-year-old Japanese man with papillary adenocarcinoma of the lung. Although the lungs are usually a target organ of cytomegalovirus infection, most organs can be involved. However, the male reproductive system has rarely been reported infected with the virus. H.E. sections of our case showed cytomegaloviral inclusions in many ductal epithelia of the seminal vesicle and ductus deferens as well as macrophages of the lungs. Immunohistochemistry using monoclonal antibody to cytomegalovirus disclosed viral antigenicity in these infected cells. Electron microscopy recovered enlarged infected cells packed with viral nucleocapsids approximately 100 nm in size. These nucleocapsids were enveloped in the cytoplasm and consistent with the Herpesviridae family. To our knowledge, our case is the first report of cytomegalovirus infection of the seminal vesicle and ductus deferens in the English and Japanese literature. | pubmed_564_3334 |
pubmed_319_4993 | In flowering plants, homologs of the Arabidopsis phosphatidylethanolamine-binding protein (PEBP) FLOWERING LOCUS T (FT) are key components in controlling flowering time. We show here that, although FT homologs are found in all angiosperms with completed genome sequences, there is no evidence to date that FT-like genes exist in other groups of plants. Through phylogeny reconstructions and heterologous expression, we examined the biochemical function of the Picea (spruces) and Pinus (pines) PEBP families - two gymnosperm taxa phylogenetically distant from the angiosperms. We have defined a lineage of gymnosperm PEBP genes, termed the FT/TERMINAL FLOWER1 (TFL1)-like genes, that share sequence characteristics with both the angiosperm FT- and TFL1-like clades. When expressed in Arabidopsis, FT/TFL1-like genes repressed flowering, indicating that the proteins are biochemically more similar to the angiosperm TFL1-like proteins than to the FT-like proteins. This suggests that the regulation of the vegetative-to-reproductive switch might differ in gymnosperms compared with angiosperms. Molecular evolution studies suggest that plasticity at exon 4 contributes to the divergence of FT-like function in floral promotion. In addition, the presence of FT-like genes in basal angiosperms indicates that the FT-like function emerged at an early stage during the evolution of flowering plants as a means to regulate flowering time. | 10.1111/j.1469-8137.2012.04332.x |
pubmed_741_6000 | Thymic cyst is a rare cause of an anterior mediastinal mass that cannot be easily differentiated from more sinister neoplastic anterior mediastinal processes on the chest radiograph. It is controversial as to whether computed tomography can make the distinction between thymic cysts and neoplastic disease. Sonography is a useful adjunct to the computed tomographic examination in determining whether or not an anterior mediastinal mass is cystic. Sonography is easily performed provided the mass is in contact with the chest wall. | 10.1016/0149-936x(83)90057-7 |
pubmed_938_4134 | Malignant disease is undoubtedly an extraordinary situation demanding trust in the relation between the patient and the doctor. From the legal aspect, any treatment and especially the surgical one is an attack on the integrity of the patient and is not allowed without the agreement of the patients. The relationship between the patient and the doctor begins with at the first consultation and should not end after discharge from hospital. Periodical examinations, repeated admissions and treatment of the malignant disease sequelae, make the relationship between the patient and the doctor a lifelong one. Laws in different countries mostly regulate the relationship between the patient and the doctor as an contract. Therefore, in order to overcome unavoidable crises especially common with malignant disease, its long duration and treatment, an exact definition of the relationship between the patient and the doctor founded on confidence and understanding is necessary. | pubmed_938_4134 |
pubmed_433_24701 | For the first time, tetrodotoxin (TTX) was detected in a bacterial strain after five years of cultivation in laboratory conditions since its isolation from the animal host. A reliable method suitable for bacterial samples, high-performance liquid chromatography with tandem mass spectrometry, was used for toxin detection in spore and vegetative cultures of Bacillus sp. 1839. TTX was detected in a spore culture of the strain. | 10.3390/md17120704 |
pubmed_38_20692 | OBJECTIVE
To evaluate the effects of Sanyinjiao (SP6) with electroacupuncture on labour pain in women during the labour process.
METHODS
A total of 350 women in labour from three centres were randomly divided into the electroacupuncture group (acupuncture group), the sham electroacupuncture group (sham group) and the control group. Women in labour in the electroacupuncture group received the electroacupuncture on the point Sanyinjiao (SP6). The analgesic effect was self-rated by women in labour, using visual analogue scale (VAS). The duration and paralysis time of uterine contraction, uterine contraction regularity, degree of cervical extension, presentation of foetal descent, the condition of intra-partum haemorrhage and postpartum haemorrhage, labour manner, lochia, involution of uterus, milk secretion, neonate Apgar Score and neonate body height and weight were also measured. All data were analysed with Statistical Package for Social Sciences (SPSS) 12.0.
RESULTS
Labour pain scores from women in the acupuncture group were less than in the control group at needle retaining at 30min, 2 and 4h after needle withdrawal. Other evaluated indices did not show significant differences among the three groups. No adverse events were observed during the labour process.
CONCLUSION
SP6 with electroacupuncture could be an effective way for decreasing labour pain. | 10.1016/j.ctim.2010.09.001 |
pubmed_734_17459 | Background
Recently, the number of available disease modifying therapies for multiple sclerosis (MS) has increased. However, a proportion of patients treated with these agents continue to experience relapses and disease progression. Cladribine tablets, approved in 2017 for highly active relapsing MS, comprise a sparsely administered oral treatment which exerts its therapeutic effect through a reduction and subsequent repletion of the lymphocyte population.
Purpose/Study Sample
Here we describe the design of CLAD CROSS, a prospective, non-interventional, multicenter, Phase IV study in patients with a confirmed diagnosis of RRMS who switch from first-line disease modifying drugs (DMDs) to treatment with cladribine tablets in routine clinical practice. 242 adult patients will be recruited in 61 sites (6 countries) over 30 months and will be followed up for 2 years following prescription of cladribine tablets per the decision of the treating physicians.
Research Design
The primary endpoint is the change in annualized relapse rate (ARR) between the 12-month pre-baseline period and over the 12-month period before end of study. Secondary endpoints are the percentage of patients with 6-month disability progression or improvement at the end of the study, measured by the Expanded Disability Status Scale, Timed 25 Foot Walk and 9-Hole Peg Test scales and quality of life, treatment satisfaction, and healthcare resource utilization, measured through the MSIS-29, TSQM 1.4, and EQ-5D-3L scales, respectively. MRI lesions will be compared in the exploratory setting between the 12-month pre-baseline period, baseline, and at years 1 and 2. Adverse events will be monitored throughout the study. Interim analyses are pre-planned when 30% and 60% of patients will complete the 12-month follow-up visit.
Conclusions
CLAD CROSS will provide efficacy data on cladribine tablets, used as a follow-up treatment to first-line DMDs in the real-world setting, will further establish its safety profile and will collect information to support pharmacoeconomic studies. | 10.1177/11795735211069441 |
pubmed_1122_5691 | The Antley-Bixler syndrome is a rare disorder with many musculoskeletal anomalies that demand orthopedic assessment. The syndrome includes skeletal, craniofacial, and urogenital anomalies. The most common skeletal deformities are radiohumeral synostosis, craniosynostosis, multiple joint contractures, and arachnodactyly. Other orthopedic manifestations that may occur are femoral bowing, ulnar bowing, camptodactyly, synostoses of carpal and tarsal bones, clubfoot, vertebral body anomalies, perinatal fractures, and advanced skeletal age. The inheritance pattern is thought to be autosomal recessive. A patient with this syndrome is described, which is the 18th of 24 reports published in the world literature. This case is compared with the other reported cases. | pubmed_1122_5691 |
pubmed_960_16212 | Noncovalent drug presentation leads to the activation of drug-specific T cells. In some patients with hypersensitivity, such a response occurs within hours even upon the first exposure to the drug. Thus, the reaction to the drug might not be due to a classical, primary response, but rather mediated by existing, preactivated T cells that are cross specific for the drug, and have an additional (peptide) specificity as well. | 10.1016/j.coi.2004.09.016 |
pubmed_491_16609 | Idiopathic scoliosis is the most frequent spinal deformity in adolescence. While its aetiology remains unclear, impairments in balance control suggest a dysfunction of the sensorimotor control mechanisms. The objective of this paper is to evaluate the ability of patients with idiopathic scoliosis to reweigh sensory information. Using a neuromechanical model, the relative sensory weighting of vestibular and proprioceptive information was assessed. Sixteen healthy adolescents and respectively 20 and 16 adolescents with mild or severe scoliosis were recruited. Binaural bipolar galvanic vestibular stimulation was delivered to elicit postural movement along the coronal plane. The kinematics of the upper body, using normalized horizontal displacement of the 7th cervical vertebra, was recorded 1s before, 2s during, and 1s following vestibular stimulation. The neuromechanical model included active feedback mechanisms that generated corrective torque from the vestibular and proprioceptive error signals. The model successfully predicted the normalized horizontal displacement of the 7th cervical vertebra. All groups showed similar balance control before vestibular stimulation; however, the amplitude (i.e., peak horizontal displacement) of the body sway during and immediately following vestibular stimulation was approximately 3 times larger in patients compared to control adolescents. The outcome of the model revealed that patients assigned a larger weight to vestibular information compared to controls; vestibular weight was 6.03% for controls, whereas it was 13.09% and 13.26% for the mild and severe scoliosis groups, respectively. These results suggest that despite the amplitude of spine deformation, the sensory reweighting mechanism is altered similarly in adolescent patients with scoliosis. | pubmed_491_16609 |
pubmed_354_25926 | Antibody-drug conjugates (ADCs) contain a disease-receptor antibody and a payload drug connected via a linker. The payload delivery depends on both tumor properties and ADC characteristics. In this study, we used different linkers, attachment sites, and doses to modulate payload delivery of several ADCs bearing maytansinoids (e.g., DM1), auristatins (e.g., MMAE), and DNA alkylating agents [e.g., pyrrolo[2,1-c][1,4]benzodiazepine-dimer (PBD)] as payloads in HER2- or CD22-expressing xenograft models. The tumor growth inhibition and ADC stability and exposure data were collected and analyzed from these dosed animals. The trend analysis suggests that intratumoral payload exposures that directly related the combination of conjugate linker and dose correlate with the corresponding efficacies of three payload types in two antigen-expressing xenograft models. These preliminary correlations also suggest that a minimal threshold concentration of intratumoral payload is required to support sustained efficacy. In addition, an ADC can deliver an excessive level of payload to tumors that does not enhance efficacy ("Plateau" effect). In contrast to tumor payload concentrations, the assessments of systemic exposures of total antibody (Tab) as well as the linker, dose, site of attachment, plasma stability, and drug-to-antibody ratio changes of these ADCs did not consistently rationalize the observed ADC efficacies. The requirement of a threshold payload concentration for efficacy is further supported by dose fractionation studies with DM1-, MMAE-, and PBD-containing ADCs, which demonstrated that single-dose regimens showed better efficacies than fractionated dosing. Overall, this study demonstrates that 1) the linker and dose together determine the tissue payload concentration that correlates with the antitumor efficacy of ADCs and 2) an ADC can deliver an unnecessary level of payload to tumors in xenograft models. | 10.1124/dmd.119.087023 |
pubmed_60_25779 | New models of gene transcriptional responses to auxin signalling in Arabidopsis are presented. This work extends a previous model of auxin signalling to include networks of gene-sets which may control developmental responses along auxin gradients. Key elements of this new study include models of signalling pathways and networks involving two Aux-IAA proteins (IAAs), auxin response factors (ARFs) and gene targets. Hypotheses for the gene network topologies which may be involved in developmental responses have been tested against experimental observations for root hair growth in particular. In studying these models, we provide a framework for the analysis of auxin signalling with multiple IAAs and ARFs, and discuss the implications of bistability in such systems. | 10.1016/j.mbs.2011.10.005 |
pubmed_1090_974 | Quarter wave matching of ultrasonic transducers with two layers (glass and parylene) were studied with computer simulation. These layers are located between the piezoelectric transducer and the acoustic load. The purpose is to achieve a short impulse response and high efficiency broadband transfer in a practical manner for high frequency transducers. The acoustic impedances of these layers were chosen based on transmission line theory. A method to measure acoustic properties of the matching layers and a method to choose the material are discussed. The advantages in using a quarter wavelength of glass and parylene as the matching layers are given. The 6 dB fractional bandwidth of the simulated transmission-reception transfer was found to be 0.75, which is a factor of at least 6 improvement over a nonmatched transducer. | pubmed_1090_974 |
pubmed_101_21152 | Anesthesia for intracranial vascular procedures is complex because it requires a balance of several competing interests and potentially can result in significant morbidity and mortality. Frequently, periods of ischemia, where perfusion must be maintained, are combined with situations that are high risk for hemorrhage. This review discusses the basic surgical approach to several common pathologies (intracranial aneurysms, arteriovenous malformations, and moyamoya disease) along with the goals for anesthetic management and specific high-yield recommendations. | 10.1016/j.anclin.2020.10.001 |
pubmed_1015_10634 | Two immunoassays are described: mixed agglutination on solid phase (MASP) and inhibition of mixed agglutination on solid phase (IMASP). The MASP assay permits detection and measurement of soluble A, B and H high molecular weight glycoproteins in secretor individuals with a sensitivity at least 800 times greater than the usual inhibition technique. Both secretors and non-secretors can be typed by the less sensitive IMASP test which also permits the detection of low molecular weight A, B and H substances. | 10.1016/0022-1759(81)90112-5 |
pubmed_730_19858 | BACKGROUND/PURPOSE
Papillary cystic neoplasms are rare pancreatic tumors that typically present in women in their third decade of life. Few cases have been reported in children.
METHODS/RESULTS
The authors report on three pediatric patients: a 10-year-old boy, an 11-year-old girl, and a 14-year-old girl. The authors have reviewed the existing literature on papillary cystic neoplasms of the pancreas and suggest that these tumors probably arise early in life, grow slowly, and metastasize infrequently.
CONCLUSION
Even when these tumors metastasize, patients seldom die as a result of the malignancy. | 10.1016/s0022-3468(98)90655-8 |
pubmed_1047_12473 | The analysis of micronuclei (MN) in cultured human lymphocytes can, in principle, detect exposure to clastogens and aneuploidogens alike. As aneuploidogens such as spindle poisons usually act on dividing cells, it is not clear how an in vivo exposure of resting peripheral lymphocytes to an aneuploidogen could be transmitted and expressed as MN in cultured lymphocytes. This question is fundamental in judging if cultured lymphocytes can be used to detect in vivo exposure to aneuploidogens. In the present study, in vivo exposure of resting lymphocytes to an aneuploidogen was simulated in vitro by a 24-h pulse treatment of human lymphocytes with vinblastine sulfate (VBL) before mitogen stimulation, followed by two washes and culture in the presence of phytohemagglutinin (PHA) for 72 h. This treatment protocol did result in an increased MN frequency, but only at the highest concentration of VBL available for analysis (100 ng/ml). A more effective response, with a significant effect already at 40 ng/ml, was obtained when the 24-h pulse treatment was started at 24 h of PHA-stimulated 72-h cultures. Still much lower concentrations of VBL (1 or 2.5 ng/ml) were effective, when the treatment, started 24 h after culture initiation, was continued for 48 or 72 h (respectively) until cell harvest. These results demonstrate that MN induction by VBL depends, as expected, on the duration and timing of exposure, reflecting the availability of dividing cells during the treatment. The positive MN response obtained in the pulse-treated unstimulated lymphocytes may reflect an effect initiated in the resting stage and retained until mitosis or residual VBL left in the cells or in the cell suspension, despite the washes. | 10.1016/0165-7992(94)90064-7 |
pubmed_722_21144 | UNLABELLED
Liver fibrosis is mediated by the transformation of hepatic stellate cells (HSC) from a quiescent to an activated state. To understand the role of HSC in liver immunity, we investigated the effect of this transition on T cell stimulation in vitro. Unlike quiescent HSC, activated HSC did not induce proliferation of antigen-specific T cells. Phenotypic analysis of quiescent and activated HSC revealed that activated HSC expressed the coinhibitory molecule B7-H4. Silencing B7-H4 by small interfering RNA (siRNA) in activated HSC restored the ability of T cells to proliferate, differentiate, and regain effector recall responses. Furthermore, expression of B7-H4 on HSC inhibits early T cell activation and addition of exogenous interleukin (IL)-2 reversed the T cell anergy induced by activated HSC.
CONCLUSION
These studies reveal a novel role for activated HSC in the attenuation of intrahepatic T cell responses by way of expression of the coinhibitory molecule B7-H4, and may provide fundamental insight into intrahepatic immunity during liver fibrogenesis. | 10.1002/hep.23953 |
pubmed_534_5500 | This study examines associations between the first experience of vaginal intercourse/tampon insertion and later experiences of vulvar pain. The study is based on questionnaire data from 1,259 Swedish female senior high-school students, aged 18 to 22 years old. Of these, 592 women reported present vulvar pain. Present vulvar pain was associated with first-time experiences of vaginal intercourse (pain, negative experience, against will) and with pain at tampon insertion. First-time experiences were also related to temporal aspects of present vulvar pain during vaginal intercourse (at the beginning, after a while during, and after). Implications of first-time experiences of vaginal intercourse for future symptoms of vulvar pain are discussed. | 10.1080/0092623X.2015.1113589 |
pubmed_266_18288 | Deviations from the optimal level of mRNA translation are linked to disorders with high rates of autism. Loss of function mutations in genes encoding translational repressors such as PTEN, TSC1, TSC2, and FMRP are associated with autism spectrum disorders (ASDs) in humans and their deletion in animals recapitulates many ASD-like phenotypes. Importantly, the activity of key translational control signaling pathways such as PI3K-mTORC1 and ERK is frequently dysregulated in autistic patients and animal models and their normalization rescues many abnormal phenotypes, suggesting a causal relationship. Mutations in several genes encoding proteins not directly involved in translational control have also been shown to mediate ASD phenotypes via altered signaling upstream of translation. This raises the possibility that the dysregulation of translational control signaling is a converging mechanism not only in familiar but also in sporadic forms of autism. Here, we overview the current knowledge on translational signaling in ASD and highlight how correcting the activity of key pathways upstream of translation reverses distinct ASD-like phenotypes. | 10.1016/j.cellsig.2020.109746 |
pubmed_271_24260 | BACKGROUND
Pierson syndrome, caused by mutations in the LAMB2 gene, was originally described as a combination of microcoria and congenital nephrotic syndrome, rapidly progressing to end-stage renal failure.
CASE-DIAGNOSIS/TREATMENT
We report a minor variant of Pierson syndrome in a teenage girl with severe myopia since early infancy and proteinuria first detected at age 6. At the age of 11 she was found to carry a unique homozygous non-truncating LAMB2 mutation in exon 2: c.T240G (p.S80R). Renal biopsy revealed mild diffuse mesangial sclerosis and residual expression of laminin β2. Today at age 14, on treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, she continues to have nephrotic range proteinuria, but a normal glomerular filtration rate.
CONCLUSIONS
LAMB2 mutations should be considered in all patients with glomerular proteinuria and abnormal ocular phenotype, irrespective of age and disease severity. | 10.1007/s00467-011-2088-2 |
pubmed_716_14706 | A major challenge in the transition to continuous biomanufacturing is the lack of process analytical technology (PAT) tools which are able to collect real-time information on the process and elicit a response to facilitate control. One of the critical quality attributes (CQAs) of interest during monoclonal antibodies production is aggregate formation. The development of a real-time PAT tool to monitor aggregate formation is then crucial to have immediate feedback and process control. Miniaturized sensors placed after each unit operation can be a powerful solution to speed up an analytical measurement due to their characteristic short reaction time. In this work, a micromixer structure capable of mixing two streams is presented, to be employed in the detection of mAb aggregates using fluorescent dyes. Computational fluid dynamics (CFD) simulations were used to compare the mixing performance of a series of the proposed designs. A final design of a zigzag microchannel with 45° angle was reached and this structure was subsequently fabricated and experimentally validated with colour dyes and, later, with a FITC-IgG molecule. The designed zigzag micromixer presents a mixing index of around 90%, obtained in less than 30 seconds. Therefore, a micromixer channel capable of a fast and efficient mixing is hereby demonstrated, to be used as a real-time PAT tool for a fluorescence based detection of protein aggregation. | 10.1002/biot.202200332 |
pubmed_353_3989 | The final products encoded by the tobacco etch virus genome arise by proteolytic cleavage of a single large polyprotein precursor. Processing of the polyprotein at several sites requires the activity of a viral protease of 49,000 molecular weight (49K). We have examined the excision of the 49K protease from polyproteins translated from defined RNA transcripts. Polyproteins containing an intact 49K protein were efficiently processed after synthesis in a rabbit reticulocyte lysate to yield the 49K product. Introduction of a single amino acid substitution (cysteine to alanine) at the putative active site of the 49K protease abolished processing, indicating that the protease was excised from the polyprotein via an autocatalytic mechanism. Release of the 49K protease was determined to require autoproteolysis, since synthetic polyproteins which contained either or both 49K cleavage sites were processed poorly, if at all, in trans reactions. Protein microsequence analysis revealed that processing in vitro occurred between a glutamine-glycine dipeptide to generate the 49K amino terminus. | 10.1016/0042-6822(87)90006-7 |
pubmed_702_14673 | CONTEXT
Knowledge of sexual and contraceptive behaviors as risk factors for STDs is largely based on women's or men's separate reports of their attitudes and behaviors. Little research has been based on couples.
METHODS
Data from the 2005-2006 National Couples Survey were used to examine the sexual risk-taking behavior of 335 dating couples. Associations between each partner's characteristics and the couple's probability of recently having had anal sex and of having done something to protect themselves from STDs were assessed using logistic regression analyses. Models included measures of power dynamics and partners' perceptions of who controls sexual and contraceptive decisions.
RESULTS
Couples in which the female partner reported that her male partner made the decisions about sex and contraception had increased probability of having had anal sex during the four weeks prior to the interview. In addition, partners' relationship power and their perception of control over sex and contraception moderated associations between couples' behavior and partners' characteristics, experiences and beliefs. For example, although couples in which the male partners had known someone with AIDS were less likely than others to engage in anal sex, that association was much greater for males with high income-and thus greater power-than for those with low income.
CONCLUSIONS
Sexual behaviors are not controlled by any one individual in a relationship; characteristics of each partner are important. Couples-based interventions that take into consideration relationship-especially power-dynamics may enable individuals to initiate and sustain safer-sex practices. | 10.1363/4107409 |
pubmed_292_13905 | OBJECTIVE
We sought to evaluate whether in addition to cortisol, catecholamines also transfer psychosocial stress indirectly to the fetus by decreasing uterine blood flow (UBF) and increasing fetal anaerobic metabolism and stress hormones.
STUDY DESIGN
Seven pregnant sheep chronically instrumented with uterine ultrasound flow probes and catheters at 0.77 gestation underwent 2 hours of psychosocial stress by isolation. We used adrenergic blockade with labetalol to examine whether decreased UBF is catecholamine mediated and to determine to what extent stress transfer from mother to fetus is catecholamine dependent.
RESULTS
Stress induced transient increases in maternal cortisol and norepinephrine (NE). Maximum fetal plasma cortisol concentrations were 8.1 ± 2.1% of those in the mother suggesting its maternal origin. In parallel to the maternal NE increase, UBF decreased by maximum 22% for 30 minutes (P < .05). Fetal NE remained elevated for >2 hours accompanied by a prolonged blood pressure increase (P < .05). Fetuses developed a delayed and prolonged shift toward anaerobic metabolism in the presence of an unaltered oxygen supply. Adrenergic blockade prevented the stress-induced UBF decrease and, consequently, the fetal NE and blood pressure increase and the shift toward anaerobic metabolism.
CONCLUSION
We conclude that catecholamine-induced decrease of UBF is a mechanism of maternal-fetal stress transfer. It may explain the influence of maternal stress on fetal development and on programming of adverse health outcomes in later life especially during early pregnancy when fetal glucocorticoid receptor expression is limited. | pubmed_292_13905 |
pubmed_90_6555 | A neuropathologic study, chiefly cerebrovascular lesions and degenerative changes, was conducted on the brains of 233 subjects 50 years of age and over among 557 autopsy cases of RERF-ABCC Hiroshima in 1972-1974. There were some discrepancies between the principal clinical diagnosis and principal pathologic diagnosis in cerebrovascular disease. For cerebral hemorrhage, 8.6% were accounted for in the clinical diagnosis of the entire subjects while only 2.1% were accounted for in the pathologic diagnosis of the same subject. The degenerative changes in the central nervous system have been increasing with age and these changes were seen more in the females than in the males. Intracerebral arteriosclerosis of a moderate extension or more existed in 36.5% of the subjects and the frequency of this disease increased with age. the frequency of cerebral infarct increased with age. The location of the infarcts was most often seen in the basal ganglia and cortex of cerebrum, the size of the cortical infarct was within 0.5 cm in diameter and multiple. The vascular lesions or degenerative changes were seen in about 74% of the brains of 50 years and over. | 10.1111/j.1440-1819.1981.tb00204.x |
pubmed_378_639 | OBJECTIVE
To investigate the effects of in vivo CD151 gene transfer on angiogenesis and heart function in rats with myocardial infarction.
METHODS
Acute myocardial infarction (AMI) was induced in male Sprague-Dawley (SD) rats by left anterior descending coronary artery ligation. The surviving rats randomly received myocardial injection of saline (MI control), pAAV-CD151 and pAAV-GFP (n = 12/group). Sham-operated rats without myocardial injection (n = 12) were taken as normal control. Four weeks later, heart function and the expression of CD151 were measured. Micro vessels density (MVD) in infarct myocardium was observed by factor VIII related antigen immunochemical staining.
RESULTS
The expression of CD151 (1.98 +/- 0.23 vs. 0.91 +/- 0.09, P < 0.01) and MVD counting [(385.4 +/- 79.9) vs. (252.5 +/- 43.0) n/mm(2), P < 0.01] in pAAV-CD151 treated MI rats were significantly higher than that in MI control group, similarly, EF (64.0 +/- 8.7)% vs. (41.5 +/- 5.0)%, P < 0.01] and dp/dt(max) (6620.2 +/- 884.6 vs. 5545.5 +/- 693.0, P < 0.01) were also significantly increased post pAAV-CD151 treatment. These parameters were not affected by pAAV-GFP treatment.
CONCLUSION
CD151 in vivo gene transfer for rats with acute myocardial infarction enhanced myocardial angiogenesis and improved left ventricular function. | pubmed_378_639 |
pubmed_1040_972 | Fulminant hepatic failure occurred in an 11 week old baby of a Caucasian mother who was hepatitis B surface antigen positive, B e antigen negative, and B e antibody positive. Infants of hepatitis B e antigen positive mothers receive immunoprophylaxis against hepatitis, unlike those born to mothers who are B e antibody positive. | 10.1136/adc.60.3.265 |
pubmed_954_1237 | Oligometastasis is a clinically distinct subset of metastasis characterized by a limited number of metastases potentially curable with localized therapies. We analyzed pathways targeted by microRNAs over-expressed in clinical oligometastasis samples and identified suppression of cellular adhesion, invasion, and motility pathways in association with the oligometastatic phenotype. We identified miR-127-5p, miR-544a, and miR-655-3p encoded in the 14q32 microRNA cluster as co-regulators of multiple metastatic pathways through repression of shared target genes. These microRNAs suppressed cellular adhesion and invasion and inhibited metastasis development in an animal model of breast cancer lung colonization. Target genes, including TGFBR2 and ROCK2, were key mediators of these effects. Understanding the role of microRNAs expressed in oligometastases may lead to improved identification of and interventions for patients with curable metastatic disease, as well as an improved understanding of the molecular basis of this unique clinical entity. | 10.18632/oncotarget.2920 |
pubmed_403_20040 | Quinoline-based fluorescent chemosensors have been extensively developed for various metal cations, but it was still rare for Pd2+-selective detection. In this work, a novel quinoline-benzimidazole conjugate containing one carboxylic acid group (QBM) was designed, and the QBM displayed highly selective fluorescence quenching response towards Pd2+ over other metal cations in aqueous solution. The fluorescence titration revealed a good linear relationship between the fluorescence intensity and the Pd2+ concentration in the range of 0.5-10 μmol L-1, with the detection limit of 0.26 μmol L-1 (S/N = 3). Fluorescence detection of Pd2+ in practical water sample was also successfully achieved. | 10.1016/j.saa.2020.119283 |
pubmed_167_7884 | Achieving parenthood is often a priority and goal for women with chronic kidney disease (CKD). It can be challenging due to medical and emotional complexities around pregnancy planning and care, increased risk of adverse maternal and fetal outcomes, fears about medications such as immunosuppressants and fetal harm, and concerns regarding the impact of pregnancy on women's kidney health. Navigating the pathways for shared decision-making regarding parenthood requires an understanding of the patient's experiences, values, priorities, and needs. In this review, we describe the patient perspective of high-risk pregnancies including those complicated by CKD and outline recommendations for counseling that incorporate these perspectives to improve the patient experience. | 10.1016/j.bpobgyn.2018.12.003 |
pubmed_751_250 | A strain of Streptococcus faecalis isolated from the urogenital flora was selected for its ability to inhibit the in vitro growth of Neisseria gonorrhoeae. Initially, the inhibitory activity was demonstrated on solid medium only when the inhibitor and the target strains were growing simultaneously, such as in the spot-lawn and flip-flop agar overlay methods. The antigonococcal effect was not due to a shift in the pH or depletion of nutrient in the medium. This activity was not produced in liquid medium nor could it be extracted in a soluble form from either the solid medium or the streptococcal cells. The production of the inhibitory activity could not be enhanced by ultraviolet irradiation or treatment with mitomycin C. The composition of the medium was found to affect the size of the inhibitory zone produced. The inhibitory activity showed a wide antigonococcal spectrum and was susceptible to trypsin and pronase but resistant to alpha- and beta-amylases and catalase. This activity passed through a filtering membrane and was also dialyzable and had an apparent molecular weight of less than 1,000. The addition of bovine serum albumin to solid medium enabled us to show an inhibition even when the producer and the target strains were grown sequentially, thus suggesting that part of the difficulty of studying such inhibitory activity could be due to its instability. | pubmed_751_250 |
pubmed_73_23 | Type III/lambda interferons (IFNs) were discovered less than a decade ago and are still in the process of being characterized. Although previous studies have focused on the function of IFN-lambda 3 (also known as interleukin (IL)-28B) in a small animal model, it is unknown whether these functions would translate to a larger, more relevant model. Thus in the present study, we have used DNA vaccination as a method of studying the influence of IFN-lambda 3 on adaptive immune responses in rhesus macaques. Results of our study show for the first time that IFN-lambda 3 has significant influence on antigen-specific CD8(+) T-cell function, especially in regards to cytotoxicity. Peripheral CD8(+) T cells from animals that were administered IFN-lambda 3 showed substantially increased cytotoxic responses as gauged by CD107a and granzyme B coexpression as well as perforin release. Moreover, CD8(+) T cells isolated from the mesenteric lymph nodes (MLN) of animals receiving IFN-lambda 3 loaded significant amounts of granzyme B upon extended antigenic stimulation and induced significantly more granzyme B-mediated cell death of peptide pulsed targets. These data suggest that IFN-lambda 3 is a potent effector of the immune system with special emphasis on CD8(+) T-cell killing functions which warrants further study as a possible immunoadjuvant. | 10.1038/mt.2010.118 |
pubmed_85_21625 | Carbon monoxide (CO) is a gaseous signaling molecule and is produced in vivo from the intracellular breakdown of heme via the heme oxygenase (HO) family of enzymes. In this study we investigated the role of the HO-1/CO system in the control of ventilation in zebrafish, Danio rerio Immunohistochemistry revealed the presence of HO-1 in the chemoreceptive neuroepithelial cells (NECs) of larvae (4 days postfertilization) and adults, indicating the potential for endogenous CO production in the NECs. Hypoxia (20 min, water Po2 of 30 mmHg) caused a significant increase in HO-1 activity in whole larvae and in the gills of adult fish. Zebrafish with reduced HO-1 activity (via HO-1 knockdown in larvae or zinc protoporphyrin IX treatment in adults) exhibited increased ventilation frequency (Vf) under normoxic but not hypoxic conditions. The addition of exogenous CO restored resting Vf in fish with diminished CO production, and in some cases (e.g., hypoxic sham larvae) CO modestly reduced Vf below resting levels. Larval fish were treated with phenylhydrazine (PHZ) to eliminate the potential confounding effects of CO-hemoglobin interactions that might influence ventilation. PHZ treatment did not cause changes in Vf of normoxic larvae, and the addition of CO to PHZ-exposed larvae resulted in a significant decrease in sham and HO-1-deficient fish under normoxic conditions. This study demonstrates for the first time that CO plays an inhibitory role in the control of breathing in larval and adult zebrafish. | 10.1152/ajpregu.00094.2016 |
pubmed_854_478 | Performance of the Roche Online KIMS (kinetic interaction of microparticles in solution) benzodiazepine (BZD) immunoassay (IA) with and without beta-glucuronidase treatment was evaluated on a Hitachi Modular automated IA analyzer calibrated using nordiazepam at 100 ng/mL. Reproducibility, linearity, accuracy, sensitivity, and interferences were evaluated. Precision of the assay (percent coefficient of variation (%CV)) with and without addition of the enzyme was less than 6% and 9%, respectively, with linearity (r(2) value of 0.9578 and 0.9746), respectively. Between-run precision of a 125 ng/mL nordiazepam control (n = 287) over 67 days, produced a %CV of 13.6% for the hydrolytic assay. Modification of the BZD assay to include automated hydrolysis of urinary BZD glucuronide conjugates was evaluated using three glucuronidated BZD standards prepared at concentrations ranging from 250 to 10,000 ng/mL. With hydrolysis, temazepam, oxazepam, and lorazepam glucuronides, produced cross-reactivities of 25%, 15%, and 20%, respectively. Without hydrolysis, the glucuronidated BZD standards produced less than 1% cross-reactivity in the assay. The ability of the assay to differentiate between positive and negative samples was evaluated by assaying 20 negative urine samples and serial dilutions of certified drug-free urine fortified with 28 different BZDs. All of the negative and positive urine samples produced the appropriate screening result. Cross-reactivities of 27 different BZDs, calculated as the normalized IA response divided by the BZD concentration that produced a response approximately equivalent to the response of a 100 ng/mL nordiazepam standard and multiplied by 100, ranged from 15% to 149%. Human urine samples (n = 28) that were previously found to contain BZDs by gas chromatography-mass spectrometry (GC-MS) also produced a positive BZD IA result. The IA was challenged with 78 potentially interfering compounds, and none produced a positive BZD response. As a part of the validation, a large number of human urine samples (29,500) were assayed using the modified Online BZD IA method to evaluate the performance of the method in production. Of the 29,500 samples tested, 80 produced a positive IA result. Analysis by GC-MS confirmed the presence of at least 1 BZD compound in 61 of the samples corresponding to a confirmation rate of 76%. The Online BZD IA modified by the automatic addition of beta-glucuronidase appears well adapted for the rapid detection of BZDs and their metabolites in human urine. | 10.1093/jat/29.3.193 |
pubmed_840_18863 | Influenza continues to be a major health concern and there is always the threat of a pandemic due to the emergence of a viral strain new to the human population, as exemplified by the avian influenza A/H5N1 virus which was responsible for six deaths in Hong Kong last year. Data reported in the past year, based on in-vitro, in-vivo (animal) and clinical studies, suggest that a new class of antiviral compounds targeting the viral neuraminidase is likely to be useful for the treatment and prevention of influenza virus infections in humans. | 10.1097/00001432-199812000-00013 |
pubmed_1132_9954 | Advanced preoperative imaging of parathyroid adenomas and intraoperative parathyroid hormone determination optimized the results in the surgical treatment of primary hyperparathyroidism patients. We asked, whether reasons for failure have changed during the last 25 years.We retrospectively analyzed operations for persistent primary hyperparathyroidism in our department between 2001 and 2011 (n=67), and compared these results to our experience between 1986 and 2001 (n=80).From 2001 to 2011, 765 primary hyperparathyroidism patients were operated on at our department. All but 4 patients were cured (761/765, 99.5%). 67 operations were performed for persistent primary hyperparathyroidism. Main reasons for failure were a misdiagnosed sporadic multiple gland disease in our own patients (18/29, 62.1%), and an undetected solitary adenoma in patients referred to us after -initial operation in another hospital (22/38, 57.9%) (statistically significant). From 1986 to 2001 (1 105 primary hyperparathyroidism patients), main indications for re-operation due to persistent disease were an undiagnosed sporadic multiple gland disease in our own patients (15/24, 62.5%), and a missed solitary adenoma in patients being operated on primarily somewhere else (38/56, 67.9%) (statistically significant).Comparing our experience in 147 patients with persistent primary hyperparathyroidism being operated on between 2001-2011 and 1986-2001, not much has changed with the modern armamentarium of improved preoperative imaging or intraoperative biochemical control. Whereas sporadic multiple gland disease was the most common reason for unsuccessful surgery in experienced hands, other units mainly failed due to an undetected solitary adenoma. Re-operations for persistent primary hyperparathyroidism performed by us were successful in 93.8% (2001-2011) and 96.0% (1986-2001), respectively. | 10.1055/s-0033-1334876 |
pubmed_878_6126 | Although glucocorticoid therapy is considered to be the main pathogenic factor, a consistent body of evidence suggests that other immunosuppressants might also play an important role in the development of the post-transplant renal osteopathy (PRO) through their pleiotropic pharmacological effects. Glucocorticoids seem to induce osteoclasts' activity suppressing the osteoblasts while data regarding other immunosuppressive drugs are still controversial. Mycophenolate mofetil and azathioprine appear to be neutral regarding the bone metabolism. However, the study analyzing any independent effect of antimetabolites on bone turnover has not been conducted yet. Calcineurin inhibitors (CNIs) induce trabecular bone loss in rodent, with contradictory results in renal transplant recipients. Suppression of vitamin D receptor is probably the underlying mechanism of renal calcium wasting in renal transplant recipients receiving CNI. In spite of an increased 1,25(OH)2 vitamin D level, the kidney is not able to reserve calcium, suggesting a role of vitamin D resistance that may be related to bone loss. More efforts should be invested to determine the role of CNI in PRO. In particular, data regarding the role of mammalian target of rapamycin inhibitors (mTORi), such as sirolimus and everolimus, in the PRO development are still controversial. Rapamycin markedly decreases bone longitudinal growth as well as callus formation in experimental models, but also lowers the rate of bone resorption markers and glomerular filtration in clinical studies. Everolimus potently inhibits primary mouse and human osteoclast activity as well as the osteoclast differentiation. It also prevents the ovariectomy-induced loss of cancellous bone by 60 %, an effect predominantly associated with a decreased osteoclast-mediated bone resorption, resulting in a partial preservation of the cancellous bone. At present, there is no clinical study analyzing the effect of everolimus on bone turnover in renal transplant recipients or comparing sirolimus versus everolimus impact on bone, so only general conclusions could be drawn. Hence, the use of mTORi might be useful in patients with PRO due to their possible potential to inhibit osteoclast activity which might lead to a decreased rate of bone resorption. In addition, it should be also emphasized that they might inhibit osteoblast activity which may lead to a decreased bone formation and adynamic bone disease. Further studies are urgently needed to solve these important clinical dilemmas. | 10.1007/s11255-013-0596-7 |
pubmed_768_25403 | Many have written of the experience of mathematical beauty as being comparable to that derived from the greatest art. This makes it interesting to learn whether the experience of beauty derived from such a highly intellectual and abstract source as mathematics correlates with activity in the same part of the emotional brain as that derived from more sensory, perceptually based, sources. To determine this, we used functional magnetic resonance imaging (fMRI) to image the activity in the brains of 15 mathematicians when they viewed mathematical formulae which they had individually rated as beautiful, indifferent or ugly. Results showed that the experience of mathematical beauty correlates parametrically with activity in the same part of the emotional brain, namely field A1 of the medial orbito-frontal cortex (mOFC), as the experience of beauty derived from other sources. | 10.3389/fnhum.2014.00068 |
pubmed_228_17765 | Adequate dialysis is difficult to define because we have not identified the toxic solutes that contribute most to uremic illness. Dialysis prescriptions therefore cannot be adjusted to control the levels of these solutes. The current solution to this problem is to define an adequate dose of dialysis on the basis of fraction of urea removed from the body. This has provided a practical guide to treatment as the dialysis population has grown over the past 25 years. Indeed, a lower limit to Kt/V(urea) (or the related urea reduction ratio) is now established as a quality indicator by the Centers for Medicare and Medicaid for chronic hemodialysis patients in the United States. For the present, this urea-based standard provides a useful tool to avoid grossly inadequate dialysis. Dialysis dosing, however, based on measurement of a single, relatively nontoxic solute can provide only a very limited guide toward improved treatment. Prescriptions which have similar effects on the index solute can have widely different effects on other solutes. The dose concept discourages attempts to increase the removal of such solutes independent of the index solute. The dose concept further assumes that important solutes are produced at a constant rate relative to body size, and discourages attempts to augment dialysis treatment by reducing solute production. Identification of toxic solutes would provide a more rational basis for the prescription of dialysis and ultimately for improved treatment of patients with renal failure. | 10.1111/j.1525-139X.2011.00979.x |
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