index
stringlengths 10
17
| text
stringlengths 101
18k
| doi
stringlengths 2
72
|
|---|---|---|
pubmed_713_20012 | Background: While case series have established the efficacy of deep brain stimulation (DBS) in treating obsessive-compulsive disorder (OCD), it has been our experience that few OCD patients present without comorbidities that affect outcomes associated with DBS treatment. Here we present our experience with DBS therapy for OCD in patients who all have comorbid disease, together with the results of our programming strategies. Methods: For this case series, we assessed five patients who underwent ventral capsule/ventral striatum (VC/VS) DBS for OCD between 2015 and 2019 at the University of Colorado Hospital. Every patient in this cohort exhibited comorbidities, including substance use disorders, eating disorder, tic disorder, and autism spectrum disorder. We conducted an IRB-approved, retrospective study of programming modifications and treatment response over the course of DBS therapy. Results: In addition to patients' subjective reports of improvement, we observed significant improvement in the Yale-Brown Obsessive-Compulsive Scale (44%), the Montgomery-Asberg Depression Rating Scale (53%), the Quality of Life Enjoyment and Satisfaction Questionnaire (27%), and the Hamilton Anxiety Rating scales (34.9%) following DBS. With respect to co-morbid disease, there was a significant improvement in a patient with tic disorder's Total Tic Severity Score (TTSS) (p = 0.005). Conclusions: DBS remains an efficacious tool for the treatment of OCD, even in patients with significant comorbidities in whom DBS has not previously been investigated. Efficacious treatment results not only from the accurate placement of the electrodes by the surgeon but also from programming by the psychiatrist. | 10.3389/fpsyt.2021.568932 |
pubmed_300_20058 | INTRODUCTION
In this article, we presented the rationale and calculation procedures of the propensity score matching (PSM), and its application in the designing stage of an epidemiological study. Based on existing observational data, PSM can be used to select one or more comparable controls for each subject in 'treatment' group according to the propensity scores estimated by 'treatment' variable and main covariates. The results of an example analysis showed that the bias for main confounders between the treated and control samples declined more than 55% after PMS.
CONCLUSION
PSM can reduce most of the confounding bias of the observational study, and can obtain approximate study effect to the randomized controlled trials when used in the designing of the epidemiological study. | pubmed_300_20058 |
pubmed_103_1077 | Nowadays, water and energy consumption is intensifying every year in most of the countries. This perpetual increase will not be supportable in the long run, making urgently to manage these resources on a sustainable way. Domestic consumptions of water and electric energy usually are related and it's important to study that relation, identifying opportunities for use efficient improvement. In fact, without an understanding of water-energy relations, there are water efficiency measures that may lead to unintentional costs in the energy efficiency field. In order to take full advantage of combined effect between water and energy water management methodologies, it is necessary to collect data to ensure that the efforts are directed through the most effective paths. This paper presents a study based in the characterization, measurement and analysis of water and electricity consumption in a single family house (2months period) in order to find an interdependent relationship between consumptions at the end user level. The study was carried out on about 200 baths, divided in four different scenarios where the influence of two variables was tested: the flow reducer valve and the bath temperature. Data showed that the presence of flow reducer valve decreased electric energy consumption and water consumption, but increased the bath duration. Setting a lower temperature in water-heater, decreased electric consumption, water consumption and bath duration. Analysing the influence of the flow reducer valve and 60°C temperature simultaneously, it was concluded that it had a significant influence on electric energy consumption and on the baths duration but had no influence on water consumption. | 10.1016/j.scitotenv.2017.02.008 |
pubmed_375_1341 | Visual tracking tests have been employed to provide a quantitative description of voluntary control of arm movement in a group of patients suffering from athetoid cerebral palsy. Voluntary control was impaired in all patients in a characteristic manner. Maximum velocity and acceleration of arm movement were reduced to about 30-50% of their values in normal subjects and the time lag of the response to a visual stimulus was two or three times greater than in normals. Tracking transmission characteristics indicated a degree of underdamping which was not presnet in normal or spastic patients. This underdamping could be responsible for a low frequency (0·3-0·6 Hz) transient oscillation in elbow-angle movements associated with sudden voluntary movement. The maximum frequency at which patients could produce a coherent tracking response was only 50% of that in normal subjects and the relationship between the electromyogram and muscle contraction indicated that the mechanical load on the biceps muscle was abnormal, possibly due to increased stiffness of joint movement caused by involuntary activity in agonist and antagonist muscles acting across the joint. | 10.1136/jnnp.37.2.162 |
pubmed_294_11559 | The short- and long-term therapeutic results of transseptosphenoidal adenomectomy were studied retrospectively in 92 patients with pituitary tumors (42 nonsecreting adenomas, 21 GH-, 15 PRL-, 10 ACTH-, 2 TSH-, and 2 FSH-secreting adenomas). Severe surgically related complications were not observed. The early remission rate was 53.7% in nonsecreting, 57.1% in GH-secreting, 60% in PRL-secreting, 88.9% in ACTH-secreting, and 75% in TSH- or FSH-secreting adenomas. The recurrence rate in patients with nonsecreting adenomas was 47.1%, with GH-secreting adenomas 10%, with ACTH-secreting adenomas 25%, and with TSH- or FSH-secreting adenomas 66.7%, respectively. A long-term cure rate of 69.2% was observed in prolactinomas in combination with a facultative dopamine agonist therapy. More patients had normal pituitary function concerning TSH, ACTH, and LH/FSH post-operatively (48.9% versus 46.6% preoperatively). These data confirm that transseptosphenoidal surgery is a safe and selective treatment for pituitary adenomas with efficient preservation of the normal pituitary gland. | pubmed_294_11559 |
pubmed_713_25404 | Measurements of canopy gas exchange of mixed communities of ryegrass (Lolium perenne L.) and white clover (Trifolium repens L.) in the field during winter showed that instantaneous rates of gross photosynthesis were usually little less than those of canopies of similar leaf area at similar irradiance in summer. Respiration rates per unit dry weight were on average 25% less than those of comparable swards in summer. The daily totals of net photosynthesis, however, were as little as a tenth of summer values, because of the short photoperiods and low average irradiance. Clover leaf area tended to be positioned lower in the canopy than grass leaf area, especially towards the end of winter, and clover had a lower rate of photosynthesis per unit leaf area in situ than grass. | 10.1111/j.1469-8137.1989.tb02404.x |
pubmed_716_19567 | Neuromedin S (NMS) is a well-known anorexigenic neuropeptide. Despite some reports of the presence of its transcript and precursor protein in testis, the expression and localization of NMS and its receptors during the postnatal development of mammalian testis remains elusive. We investigated the expression patterns and testicular localization of NMS and its receptors NMUR1 and NMUR2, during 5, 10, 20, 30, and 90 days of postnatal development, using real time PCR, immunoblot analysis and immunohistochemistry in mice. NMS and its receptors are present at all age groups at transcript level in mouse testis. At the protein level, NMS and NMUR2 are present in all age groups, whereas NMUR1 is present primarily in 30- and 90-day testis. Immunolocalization study showed that NMS and NMUR2 are expressed in spermatogonia, spermatocytes, Sertoli cells, and Leydig cells, in contrast to NMUR1 which is expressed exclusively in the Leydig cells of 30- and 90-day testis. The results also confirm the intranuclear localization of NMS in spermatogonia and spermatocytes. Although NMS-NMUR2 is expressed in Sertoli cells at all stages of the spermatogenic cycle, they showed a stage-specific expression pattern in spermatogonia and primary spermatocytes. In conclusion, NMS and its receptors NMUR1 and NMUR2 are expressed in the testis and may regulate spermatogenesis, possibly by modulating steroidogenesis and Sertoli cell function in the testis. | 10.1016/j.peptides.2022.170899 |
pubmed_660_5594 | With the notable exception of B-cell malignancies, the efficacy of chimeric antigen receptor (CAR) T cells has been limited, and CAR T cells have not been shown to expand and persist in patients with nonlymphoid tumors. Here we demonstrate that redirection of primary human T cells with a CAR containing the inducible costimulator (ICOS) intracellular domain generates tumor-specific IL-17-producing effector cells that show enhanced persistence. Compared with CARs containing the CD3ζ chain alone, or in tandem with the CD28 or the 4-1BB intracellular domains, ICOS signaling increased IL-17A, IL-17F, and IL-22 following antigen recognition. In addition, T cells redirected with an ICOS-based CAR maintained a core molecular signature characteristic of TH17 cells and expressed higher levels of RORC, CD161, IL1R-1, and NCS1. Of note, ICOS signaling also induced the expression of IFN-γ and T-bet, consistent with a TH17/TH1 bipolarization. When transferred into mice with established tumors, TH17 cells that were redirected with ICOS-based CARs mediated efficient antitumor responses and showed enhanced persistence compared with CD28- or 4-1BB-based CAR T cells. Thus, redirection of TH17 cells with a CAR encoding the ICOS intracellular domain is a promising approach to augment the function and persistence of CAR T cells in hematologic malignancies. | 10.1182/blood-2013-10-535245 |
pubmed_915_5038 | Aims: To explore the roles and regulatory mechanisms of the circular RNA (circRNA)-hsa-circ-0072309 in CAKI-1 and ACHN cells. Methods: CAKI-1 and ACHN cells were transfected with hsa-circ-0072309 overproduction vector (circRNA) and microRNA-100 (miR-100) mimic or the corresponding controls. Cell viability was detected with the CCK-8. The protein expression levels of p53, c-Myc, cleaved-caspase-3/9, matrix metalloproteinase (MMP)-2/9, vimentin, AKT, PI3K and mTOR were individually determined through western blot. qRT-PCR was used to examine the expressions of hsa-circ-0072309 and miR-100. The apoptotic rate and the migration or invasion rates were separately determined by the annexin v-FITC/PI with a flow cytometer and modified two-chamber migration assay or millicell hanging cell culture. Results: The hsa-circ-0072309 was poorly expressed in tumor tissue. Abundant hsa-circ-0072309 induced the inhibitions of cell proliferation, migration and invasion, as well as the PI3K/AKT and the mTOR cascades but enhancement of apoptosis. circRNA stimulated the down-regulation of miR-100, which was low-expressed in tumour tissue and whose overproduction abolished the impacts of circRNA on these elements mentioned above. Conclusion: The hsa-circ-0072309 played anti-tumour roles by targeting miR-100 by blocking the PI3K/AKT and mTOR cascades in the CAKI-1 and ACHN cell lines. | 10.1080/21691401.2019.1657873 |
pubmed_161_128 | Seventeen proven cases of complete hydatidiform mole and 14 sonographically similar nonmolar cases were studied in detail with a variety of ultrasound transducers. Complete hydatidiform moles can be reliably differentiated from other lesions with similar sonographic appearances by using a highly focused ultrasound transducer to image the near field of the intrauterine contents. | 10.2214/ajr.140.2.307 |
pubmed_99_4744 | A classification of chronic left ventricular insufficiency of the congestive type associated with coronary heart disease has been elaborated on the basis of the results provided by clinical and hemodynamic studies as well as by the examination of the degree of pulmonary hydration using roentgenologic and radionuclide biindicator methods for evaluating the amount of the extravascular fluid in the lungs. Recommendations are offered as to the treatment of every stage of chronic left ventricular insufficiency. | pubmed_99_4744 |
pubmed_156_20897 | OBJECTIVE
This retrospective review of patients undergoing total laparoscopic hysterectomy examines whether differences in outcomes exist on the basis of body mass index (BMI).
METHODS
All cases of total laparoscopic hysterectomy performed from September 1996 to July 2002 for benign diagnoses, and microinvasive cervical, early endometrial, and occult ovarian carcinoma were reviewed. There were 330 patients analyzed by BMI category (range, 18.5-54.1): ideal (n = 150) less than 24.9 kg/m(2), overweight (n = 95) 25 to 29.9 kg/m(2), and obese (n = 78) 30 kg/m(2) or more. Seven patients were converted to laparotomy (four ideal BMI, two overweight, one obese) leaving 323 (98%) for analysis. Mean age (50 years), height (65 in.), and parity (1.2) were similar, with 39% nulligravidas in each group.
RESULTS
Mean operating time (156 minutes), blood loss (160 mL), and length of hospital stay (1.9 days) did not vary by BMI group. Total complication rates (8.9%), and major (5.5%) and minor (3.4%) complication rates were similar in each BMI group. Urologic injury was observed in 3.1%, with two-thirds occurring in the first one-third of the patient series.
CONCLUSION
Total laparoscopic hysterectomy is feasible and safe, resulting in short hospital stay, minimal blood loss, and minimal operating time for patients in all BMI groups. The laparoscopic approach may extend the benefits of minimally invasive hysterectomy to the very obese, for whom abdominal surgery poses serious risk. | 10.1016/j.obstetgynecol.2003.08.018 |
pubmed_394_7228 | The influence of pi-interactions with a His ligand have been investigated in a family of copper-containing redox metalloproteins. The Met16Phe and Met16Trp pseudoazurin, and Leu12Phe spinach and Leu14Phe Phormidium laminosum plastocyanin variants possess active-site pi-contacts between the introduced residue and His81 and His87/92 respectively. The striking overlap of the side chain of Phe16 in the Met16Phe variant and that of Met16 in wild type pseudoazurin identifies that this position provides an important second coordination sphere interaction in both cases. His-ligand protonation and dissociation from Cu(I) occurs in the wild type proteins resulting in diminished redox activity, providing a [H(+)]-driven switch for regulating electron transfer. The introduced pi-interaction has opposing effects on the pKa for the His ligand in pseudoazurin and plastocyanin due to subtle differences in the pi-contact, stabilizing the coordinated form of pseudoazurin whereas in plastocyanin protonation and dissociation is favored. Replacement of Pro36, a residue that has been suggested to facilitate structural changes upon His ligand protonation, with a Gly, has little effect on the pKa of His87 in spinach plastocyanin. The mutations at Met16 have a significant influence on the reduction potential of pseudoazurin. Electron self-exchange is enhanced, whereas association with the physiological partner, nitrite reductase, is only affected by the Met16Phe mutation, but kcat is halved in both the Met16Phe and Met16Trp variants. Protonation of the His ligand is the feature most affected by the introduction of a pi-interaction. | 10.1021/ja8038135 |
pubmed_693_4484 | Chick heart explants stimulate a dense outgrowth of neurites in co-cultured spinal, sympathetic and ciliary ganglia. A factor sharing these properties was partially purified by gel filtration of extract prepared from lyophilized 18-day embryonic hearts. The active factor has an apparent molecular weight of roughly 40,000 and is evidently distinct from nerve growth factor (NGF) by stimulating the parasympathetic ciliary neurons and by lack of cross-reactivity with antibodies to NGF. | 10.1016/0304-3940(79)95350-3 |
pubmed_396_14359 | Streptogramins represent a unique class of antibiotics remarkable for their antibacterial activity and their unique mechanism of action. These antibiotics are produced naturally as secondary metabolites by a number of Streptomyces species and have been classified into two main groups. They consist of at least two structurally unrelated compounds, group A or M (macrolactones) and group B or S (cyclic hexadepsipeptides). Both groups bind bacterial ribosomes and inhibit protein synthesis at the elongation step and they act synergistically in vitro against many microorganisms. Streptogramins A and B act synergistically in vivo; the mixture of the two compounds is more powerful than the individual components and their combined action is irreversible. The pharmacokinetic parameters of group A and B streptogramins in blood are similar. The major gap, limiting the therapeutic use of the natural compounds, was represented by the lack dissolution in water. The synthesis of water-soluble derivatives of pristinamycin I(A) and II(B) has allowed the development of injectable, first represented by quinupristin/dalfopristin (Synercid) and oral formulations, represented by RPR-106972, streptogramins with fixed compositions. Streptogramins have demonstrated activity against Gram-positive microorganisms in vitro and in vivo, including those with multi-drug resistance. Moreover, the absence of cross-resistance to macrolides in many of these microorganisms and the rarity of cross-resistance between the two groups of antibiotics associated with the rapid bacterial killing are the principal features of the streptogramins, offering the possibility for treating the rising number of infections that are caused by multi-resistant Gram-positive bacteria. | 10.1517/13543784.10.2.185 |
pubmed_1088_2451 | One of the major challenges in post-genomic research is to understand how physiological and pathological phenotypes arise from the networks or connectivity of expressed genes. In addressing this issue, we have developed two computational algorithms, CoExMiner and PathwayPro, to explore static features of gene co-expression and dynamic behaviors of gene networks. CoExMiner is based on B-spline approximation followed by the coefficient of determination (CoD) estimation for modeling gene co-expression patterns. The algorithm allows the exploration of transcriptional responses that involve coordinated expression of genes encoding proteins which work in concert in the cell. PathwayPro is based on a finite-state Markov chain model for mimicking dynamic behaviors of a transcriptional network. The algorithm allows quantitative assessment of a wide range of network responses, including susceptibility to disease, potential usefulness of a given drug, and consequences of such external stimuli as pharmacological interventions or caloric restriction. We demonstrated the applications of CoExMiner and PathwayPro by examining gene expression profiles of ligands and receptors in cancerous and non-cancerous cells and network dynamics of the leukemia-associated BCR-ABL pathway. The examinations disclosed both linear and nonlinear relationships of ligand-receptor interactions associated with cancer development, identified disease and drug targets of leukemia, and provided new insights into biology of the diseases. The analysis using these newly developed algorithms show the great usefulness of computational systems biology approaches for biological and medical research. | 10.1007/978-1-59745-243-4_12 |
pubmed_168_5935 | Amiodarone (AMD) is a benzofurane derivative with class III antiarrhythmic activity that is effective in controlling intractable cardiac arrhythmias. One of the most common and serious drug interactions in clinical practice is the interaction between digoxin and an antiarrhythmic agent. It has been reported that AMD and N-monodesethylamiodarone (DEA), the active metabolite of AMD, inhibit the P-glycoprotein (P-gp/MDR1)-mediated digoxin transport. However, the intestinal transport processes of AMD and DEA have not been fully revealed. In this study, we focused on the intestinal transport mechanism of DEA and characterized the intestinal transport of DEA using Caco-2 cells. Basal-to-apical transport of DEA by Caco-2 cells was greater than apical-to-basal transport. The relationship between concentration and basal-to-apical flux rate appeared to approach saturation. The uptake of DEA by Caco-2 cells was increased in the presence of typical ATP-depletion compounds and thyroid hormones. On the other hand, substrates for P-gp, multidrug resistance-associated proteins (MRPs/ABCCs) and breast cancer resistance protein (BCRP/ABCG2) had no effect on the efflux of DEA. These results suggest that an ATP-binding cassette (ABC) transporter, which is different from P-gp, MRPs and BCRP, mediates the efflux of DEA across the apical membrane in Caco-2 cells and that thyroid hormone inhibits this transporter. | 10.2133/dmpk.22.307 |
pubmed_626_3710 | Mutations in the NHS (Nance-Horan Syndrome) gene lead to severe congenital cataracts, dental defects and sometimes mental retardation. NHS encodes two protein isoforms, NHS-A and -1A that display cell-type dependent differential expression and localization. Here we demonstrate that of these two isoforms, the NHS-A isoform associates with the cell membrane in the presence of intercellular contacts and it immunoprecipitates with the tight junction protein ZO-1 in MDCK (Madin Darby Canine Kidney) epithelial cells and in neonatal rat lens. The NHS-1A isoform however is a cytoplasmic protein. Both Nhs isoforms are expressed during mouse development. Immunolabelling of developing mouse with the anti-NHS antibody that detects both isoforms revealed the protein in the developing head including the eye and brain. It was primarily expressed in epithelium including neural epithelium and certain vascular endothelium but only weakly expressed in mesenchymal cells. In the epithelium and vascular endothelium the protein associated with the cell membrane and co-localized with ZO-1, which indirectly indicates expression of the Nhs-A isoform in these structures. Membrane localization of the protein in the lens vesicle similarly supports Nhs-A expression. In conclusion, the NHS-A isoform of NHS is a novel interactor of ZO-1 and may have a role at tight junctions. This isoform is important in mammalian development especially of the organs in the head. | 10.1016/j.yexcr.2009.05.008 |
pubmed_808_2290 | Intracardiac echocardiography (ICE) is an excellent ultrasound modality that can be used to guide atrial septal defect (ASD) closure. Compared with transesophageal echocardiography, ICE offers better imaging of the posterior inferior septum, it does not require deep or general anesthesia, and it allows the operator total control over image acquisition. This latter advantage requires that the operator become an expert in image acquisition and interpretation. The following is intended to serve as a primer on performance and interpretation of ICE to guide ASD closure. | 10.14797/mdcj-10-2-88 |
pubmed_512_25247 | Injectable hydrogels can be used to deliver drugs in situ over a sustained period of time. We hypothesized that sustained delivery of interleukin-10 (IL-10) following acute kidney injury (AKI) would mitigate the local and systemic proinflammatory cascade induced by AKI and reduce subsequent fibrosis. Wild-type C57BL/6 mice underwent ischemia-reperfusion AKI with avertin anesthesia. Three days later, mice were treated with either hyaluronic acid injectable hydrogel with or without IL-10, or IL-10 suspended in saline, injected under the capsule of the left kidney, or hydrogel with IL-10 injected subcutaneously. Untreated AKI served as controls. Serial in vivo optical imaging tracked the location and degradation of the hydrogel over time. Kidney function was assessed serially. Animals were killed 28 days following AKI and the following were evaluated: serum IL-6, lung inflammation, urine neutrophil gelatinase-associated lipocalin, and renal histology for fibroblast activity, collagen type III deposition and fibrosis via Picrosirius Red staining and second harmonic imaging. Our model shows persistent systemic inflammation, and renal inflammation and fibrosis 28 days following AKI. The hydrogels are biocompatible and reduced serum IL-6 and renal collagen type III 28 days following AKI even when delivered without IL-10. Treatment with IL-10 reduced renal and systemic inflammation, regardless of whether the IL-10 was delivered in a sustained manner via the injectable hydrogel under the left kidney capsule, as a bolus injection via saline under the left kidney capsule, or via the injectable hydrogel subcutaneously. Injectable hydrogels are suitable for local drug delivery following renal injury, are biocompatible, and help mitigate local and systemic inflammation. | 10.1152/ajprenal.00579.2015 |
pubmed_239_23684 | The near and far fields of a finite conductivity metallic grating with symmetrical triangular facets, used in Littrow mount, are studied. A new Green's function approach, based on the Hertz vector, is introduced and used to propagate throughout a two-dimensional domain. The field quantity of primary interest is Poynting's vector; however, the stored power is also calculated. In assessing the fields generated by the propagator, a quasi-periodic dependence of output characteristics on the grating depth to period ratio, discussed in the literature, is also found in the present study. With a plane wave incident on the grating, geometrical relationships between the incident wave vector and the grating surfaces have interesting consequences. | 10.1364/AO.56.003293 |
pubmed_292_4830 | The purpose of this study was to evaluate the probiotic properties of Enterococcus strains isolated from traditional naturally fermented cream in China. Four Enterococcus isolates showed high cholesterol removal ability in media were identified as Enterococcus durans (KLDS 6.0930 and 6.0933) and Enterococcus faecalis (KLDS 6.0934 and 6.0935) by 16S rRNA and pheS gene sequences, respectively, and selected for further evaluation. In order to assess the probiotic potential and safety of these strains, the property of four Enterococcus strains were examined, including acid and bile tolerance, adherence to Caco-2 cells and antibiotics susceptibility. All four strains showed potential cholesterol assimilation, de-conjugation of bile salts and/or cholesterol degradation to remove cholesterol in vitro. In addition, the potential effect of E. durans KLDS 6.0930 on serum cholesterol levels was evaluated in Sprague-Dawley rats. After 4 weeks administration, compared with rats fed a high-cholesterol diet without lactic acid bacteria supplementation, there was a significant (P < 0.05) decrease in the total cholesterol and low-density lipoprotein cholesterol levels in the serum of rats treated with KLDS 6.0930. Furthermore, total bile acid level in the feces was significantly (P < 0.05) increased after KLDS 6.0930 administration. These observations suggested that the strain E. durans KLDS 6.0930 may be used in the future as a good candidate for lowering human serum cholesterol levels. | 10.1111/1751-7915.12306 |
pubmed_407_6571 | Recent scientific advances mean the widespread introduction of non-invasive prenatal diagnosis (NIPD) for chromosomal aneuploidies may be close at hand, raising the question of how NIPD should be introduced as part of antenatal care pathways for pregnant women. In this paper, the authors examine the ethical implications of three hypothetical models for using NIPD for aneuploidy in state-funded healthcare systems and assess which model is ethically preferable. In comparing the models, the authors consider their respective timings; how each model would fit with current screening and diagnostic tests offered to pregnant women; the implications of offering NIPD at different stages of pregnancy; and the potential for each model to support reproductive autonomy and informed decision-making. The authors conclude by favouring a model that would be offered at 11-13 weeks gestation, alongside existing combined screening, provided that this is accompanied by measures to maximise informed decision-making, for example, provision of adequate pretest and post-test counselling. | 10.1136/medethics-2011-100180 |
pubmed_121_16091 | Amnestic-type mild cognitive impairment (a-MCI) represents the prodromal phase of Alzheimer's disease associated with a high conversion rate to dementia and serves as a potential golden period for interventions. In our study, we analyzed the role of visuospatial (VS) functions and networks in the recognition of a-MCI. We examined 78 participants (32 patients and 46 controls) in a double-center arrangement using neuropsychology, structural, and resting-state functional MRI. We found that imaging of the lateral temporal areas showed strong discriminating power since in patients only the temporal pole (F = 5.26, p = 0.034) and superior temporal gyrus (F = 8.04, p < 0.001) showed reduced cortical thickness. We demonstrated significant differences between controls and patients in various neuropsychological results; however, analysis of cognitive subdomains revealed that the largest difference was presented in VS skills (F = 8.32, p < 0.001). Functional connectivity analysis of VS network showed that patients had weaker connectivity between the left and right frontotemporal areas, while stronger local connectivity was presented between the left frontotemporal structures (FWE corrected p < 0.05). Our results highlight the remarkable potential of examining the VS system in the early detection of cognitive decline. Since resting-state setting of functional MRI simplifies the possible automatization of data analysis, detection of VS system alterations might provide a non-invasive biomarker of a-MCI. | 10.3389/fnagi.2022.854368 |
pubmed_111_2713 | By intravenous (bolus) administration of large amounts (29 Mega Units) of lymphoblastoid interferon into rabbits, it has been possible to detect circulating antiviral activity (0.02% of the dose) up to 18 hr post-injection and to determine for the first time the pharmacokinetic parameters. The slow component (elimination phase) has a half-life of 235 +/- 9 min. The total apparent volume of distribution is 2,564 +/- 1,497 ml which is far larger than the combined plasma-extracellular volumes. This suggests a IFN dilution due to its extensive binding to cell receptors. The clearance of 7.3 +/- 4.1 ml/min is an index of the rate of renal and cellular (internalization of the receptor-ligand complex) catabolism of IFN. Pharmacokinetic parameters are useful for devising an administration schedule of IFN as an antiproliferative agent but are not predictive of an immunological response if IFN is used as an immuno-adjuvant. | 10.1016/0306-3623(85)90083-7 |
pubmed_28_14451 | Mahalanobis-Taguchi System (MTS) is an effective algorithm for dimensionality reduction, feature extraction and classification of data in a multidimensional system. However, when applied to the field of high-dimensional small sample data, MTS has challenges in calculating the Mahalanobis distance due to the singularity of the covariance matrix. To this end, we construct a modified Mahalanobis-Taguchi System (MMTS) by introducing the idea of proper orthogonal decomposition (POD). The constructed MMTS expands the application scope of MTS, taking into account correlations between variables and the influence of dimensionality. It can not only retain most of the original sample information features, but also achieve a substantial reduction in dimensionality, showing excellent classification performance. The results show that, compared with expert classification, individual classifiers such as NB, RF, k-NN, SVM and superimposed classifiers such as Wrapper + RF, MRMR + SVM, Chi-square + BP, SMOTE + Wrapper + RF and SMOTE + MRMR + SVM, MMTS has a better classification performance when extracting orthogonal decomposition vectors with eigenvalues greater than 0.001. | 10.3934/mbe.2021023 |
pubmed_665_16780 | All heat exchangers (HE) in membrane oxygenators are tested by the manufacturer for water leaks during the production phase. However, for safety reasons, it is highly recommended that HEs be tested again before clinical use. The most common method is to attach the heater-cooler to the HE and allow the water to recirculate for at least 10 min, during which time a water leak should be evident. To improve the detection of water leaks, a test was devised using a pressure manometer with an integrated bulb used to pressurize the HE with air. The cardiopulmonary bypass system is set up as per protocol. A pressure manometer adapted to a 1/2" tubing is connected to the water inlet side of the oxygenator. The water outlet side is blocked with a short piece of 1/2" deadend tubing. The HE is pressurized with 250 mmHg for at least 30 sec and observed for any drop. Over the last 2 years, only one oxygenator has been detected with a water leak in which the air-method leaktest was performed. This unit was sent back to the manufacturer who confirmed the failure. Even though the incidence of water leaks is very low, it does occur and it is, therefore, important that all HEs are tested before they are used clinically. This method of using a pressure manometer offers many advantages, as the HE can be tested outside of the operating room (OR), allowing earlier testing of the oxygenator, no water contact is necessary, and it is simple, easy and quick to perform. | 10.1191/0267659106pf856oa |
pubmed_1044_21353 | Liquid crystal elastomer (LCE) is a promising candidate for actuation in light-driven soft robot applications. Due to the fact that LCE has complex hysteretic nonlinearities, which are highly dependent on the environment, modeling of actuators made of LCE is a very challenging issue. In this article, a model is proposed to describe the deformation of the LCE actuator accurately and analytically by considering the dynamic phase transition process of LCE molecules. First, an overview of the physical process of LCE's deformation is presented, and the schematic of the LCE actuator, as well as the modeling scheme are then introduced. Next, a thermodynamic analysis of the system's free energy is performed to establish the model for the LCE actuator, which gives the relationship between the system's deformation and the temperature. Here, to describe the complex hysteretic nonlinearity in the model, the dynamic process of the phase transition of LCE molecules is exploited. To effectively identify the model parameters, a two-step parameter identification strategy based on the differential evolution algorithm and nonlinear least-squares method is utilized. Finally, experimental results verify the validity of the proposed model. This modeling provides an approach to describe LCE's deformation with high accuracy and can fully reflect the physical nature of LCE's deformation, especially hysteresis. It can be utilized as a basis for accurate control over LCE actuators in photoresponsive soft robot applications. | 10.1109/TCYB.2022.3179433 |
pubmed_982_4214 | BACKGROUND
Moderately displaced two-fragment fractures of the radial head have been treated predominantly nonoperatively. Recently, however, open reduction and internal fixation has gradually gained interest, without clear evidence that initial nonoperative treatment leads to an unfavorable outcome. As a consequence, the purpose of the present study was to evaluate the long-term outcome after the initial nonoperative treatment of this type of fracture.
METHODS
Fifteen men and thirty-four women, with a mean age of forty-nine years at the time of the injury, were included in the study. All patients initially had been managed nonoperatively for a two-fragment fracture of the radial head that was displaced 2 to 5 mm and that included >/=30% of the joint surface (a Mason type-IIa fracture). Early mobilization had been used for twenty-seven patients, and cast immobilization for a mean of two weeks (range, one to four weeks) had been used for twenty-two. All patients were reevaluated with a questionnaire after a mean of nineteen years, and thirty-four also had a clinical and a radiographic evaluation. Six patients had had a delayed radial head excision because of an unsatisfactory primary outcome.
RESULTS
Forty of the forty-nine patients had no subjective complaints, eight were slightly impaired as the result of occasional elbow pain, and one had daily pain. Flexion was slightly impaired in the injured elbows as compared with the uninjured elbows (137 degrees +/- 8 degrees compared with 139 degrees +/- 7 degrees ), as was extension (-3 degrees +/- 7 degrees compared with 1 degrees +/- 5 degrees ) and supination (86 degrees +/- 7 degrees compared with 88 degrees +/- 4 degrees ) (p < 0.05 for all comparisons). The prevalence of degenerative changes on radiographs was higher for the injured elbows than for the uninjured elbows (82% [twenty-eight of thirty-four] compared with 21% [seven of thirty-four]; p < 0.01).
CONCLUSIONS
The initial nonoperative treatment of Mason type-IIa fractures of the radial head that are displaced by 2 to 5 mm is associated with a predominantly favorable outcome, especially if a delayed radial head excision is performed in the few cases in which the early outcome is unsatisfactory.
LEVEL OF EVIDENCE
Therapeutic Level IV. | 10.2106/JBJS.E.01052 |
pubmed_151_9980 | Cardiovascular disease may be associated with several comorbidities, including diabetes mellitus, thyroid disorders, and the metabolic syndrome, which are predominantly observed in women and often starting at particular ages. In addition, common treatment options for carcinomas frequently seen in women may induce serious cardiotoxic effects. We review the scope of the problem, the pathophysiologic mechanisms involved, as well as the resulting abnormalities regarding cardiac structure and function as observed by using imaging techniques. | 10.1007/978-3-319-77932-4_29 |
pubmed_588_8082 | BACKGROUND
Soil organic carbon (SOC) represents a significant pool of carbon within the biosphere. Climatic shifts in temperature and precipitation have a major influence on the decomposition and amount of SOC stored within an ecosystem and that released into the atmosphere. We have linked net primary production (NPP) algorithms, which include the impact of enhanced atmospheric CO2 on plant growth, to the SOCRATES terrestrial carbon model to estimate changes in SOC for the Australia continent between the years 1990 and 2100 in response to climate changes generated by the CSIRO Mark 2 Global Circulation Model (GCM).
RESULTS
We estimate organic carbon storage in the topsoil (0-10 cm) of the Australian continent in 1990 to be 8.1 Gt. This equates to 19 and 34 Gt in the top 30 and 100 cm of soil, respectively. By the year 2100, under a low emissions scenario, topsoil organic carbon stores of the continent will have increased by 0.6% (49 Mt C). Under a high emissions scenario, the Australian continent becomes a source of CO2 with a net reduction of 6.4% (518 Mt) in topsoil carbon, when compared to no climate change. This is partially offset by the predicted increase in NPP of 20.3%
CONCLUSION
Climate change impacts must be studied holistically, requiring integration of climate, plant, ecosystem and soil sciences. The SOCRATES terrestrial carbon cycling model provides realistic estimates of changes in SOC storage in response to climate change over the next century, and confirms the need for greater consideration of soils in assessing the full impact of climate change and the development of quantifiable mitigation strategies. | 10.1186/1750-0680-1-14 |
pubmed_86_17616 | Thirty two mouse ascitic fluids containing monoclonal antibodies (MAbs) directed against the hexon of human adenovirus type 1 were examined. The type and degree of cross-reactivity (CR) of the MAbs were determined by ELISA and hemagglutination methods with 10 heterologous hexon types. The similarity and the dissimilarity of the MAbs was also characterized by the correlation coefficient calculated from their reactivity values. On the basis of these, the 32 MAbs could be divided into five groups and fourteen individual MAbs, which altogether recognized 19 distinct epitopes. One of the recognized epitopes is the genus specific epitope of adenovirus hexons; the others are interspecies specific ones which can be found on the surface of the different hexon types in characteristic, mosaic-like combinations. The type and degree of CR of the MAbs lead to the conclusion that there exists a close antigenic relationship among the members of subgenus C of human adenoviruses and there is also a definite antigenic relationship between subgenera C and D. Hexons belonging to the oncogenic subgenera A and B display a much looser antigenic relationship with subgenus C. | 10.1007/BF01310543 |
pubmed_335_12780 | Hydrothermal reduction is a promising approach for graphene oxide (GO) reduction since it is environmentally friendly, simple, and cost effective. We present a detailed study of structural changes occurring in graphene oxide during the reduction process. The correlations between the interlayer spacing, chemical states, work functions, surface morphology, level of disorders, the number of layers, and processing time are elucidated. The results reveal that GO flakes remain in the early stage of the reduction process and that they are fully reduced after a 4-h hydrothermal treatment. With an increase in the reduction time, the resulting product, i.e., reduced graphene oxide, has a low oxygen content, small interlayer spacing, and crumbled and wrinkled structures. We are convinced that these properties can be tuned to a desired level for various applications. | 10.1038/s41598-018-25194-1 |
pubmed_757_16892 | In the Panax notoginseng quality intelligent management system, the big roots and fibrous roots cannot be cut automatically because the machine cannot distinguish the taproot, big roots, and fibrous roots of Panax notoginseng, resulting in the automatic cutting mechanism unable to obtain the control trajectory coordinate reference of the tool feed. To solve this problem, this paper proposes a visual optimal network model detection method, which uses the image detection method of marking anchor frames to improve the detection accuracy. A variety of deep learning network models are modified by the TensorFlow framework, and the best training model is optimized by comparing the results of training, testing, and verification data. This model is used to automatically identify the taproots and provide the control trajectory coordinate reference for the actuator that cuts big roots and fibrous roots automatically. The experimental results show that the optimal network model studied in this paper is effective and accurate in identifying the taproots of Panax notoginseng. | 10.1155/2021/8292535 |
pubmed_944_12857 | OBJECTIVES
Hospitals are being required to report publically their adjusted mortality rates, which are then being used to rank hospitals. Our objectives were to assess the statistical reliability of the determination of a hospital's adjusted mortality rate, of comparisons of that rate with the rates of other hospitals, and of the use of those rates to rank the hospitals.
METHODS
A cross-sectional study of 473 383 patients discharged from 42 US children's hospitals in 2008 was performed. Hospital-specific observed/expected (O/E) mortality rate ratios and corresponding hospital rankings, with 95% confidence intervals (CIs), were examined.
RESULTS
Hospitals' O/E mortality rate ratios exhibited wide 95% CIs, and no hospital was clearly distinguishable from the other hospitals' aggregated mean mortality performance. Only 2 hospitals' mortality performance fell outside the comparator hospitals' 95% CI. Those hospitals' 95% CIs overlapped with the overall comparator set's 95% CI, which suggests that there were no statistically significant hospital outliers. Fourteen (33.3%) of the 42 hospitals had O/E ratios that were not statistically different from being in the 95% CI of the top 10% of hospitals. Hospital-specific mortality rate rankings displayed even broader 95% CIs; the typical hospital had a 95% CI range that spanned 22 rank-order positions.
CONCLUSION
Children's hospital-specific measures of adjusted mortality rate ratios and rankings have substantial amounts of statistical imprecision, which limits the usefulness of such measures for comparisons of quality of care. | 10.1542/peds.2010-3074 |
pubmed_958_21304 | This paper arises out of two workshop sessions held at the fourth meeting of the Federation of Infection Societies, Manchester, 1997. The aims of the workshops were, first, to identify the factors which impede the process of translating research findings into infection control practice and second, to suggest how these barriers may be overcome. Key points from the workshops are presented within an idealized framework of creating, implementing and maintaining evidence-based infection control practice. This lends structure to our exploration of the evidence underlying infection control guidance and the reasons why such guidance often does not result in appropriate action by healthcare workers. The strengths and weaknesses of each stage of the process are examined, using examples provided by participants at the workshop. | 10.1053/jhin.1999.0587 |
pubmed_421_13962 | At present, the global pandemic as it relates to novel coronavirus pneumonia is still a very difficult situation. Due to the recent outbreak of novel coronavirus pneumonia, novel chest X-ray (CXR) images that can be used for deep learning analysis are very rare. To solve this problem, we propose a deep learning framework that integrates a convolutional neural network and a capsule network. DenseCapsNet, a new deep learning framework, is formed by the fusion of a dense convolutional network (DenseNet) and the capsule neural network (CapsNet), leveraging their respective advantages and reducing the dependence of convolutional neural networks on a large amount of data. Using 750 CXR images of lungs of healthy patients as well as those of patients with other pneumonia and novel coronavirus pneumonia, the method can obtain an accuracy of 90.7% and an F1 score of 90.9%, and the sensitivity for detecting COVID-19 can reach 96%. These results show that the deep fusion neural network DenseCapsNet has good performance in novel coronavirus pneumonia CXR radiography detection. | 10.1016/j.compbiomed.2021.104399 |
pubmed_443_331 | In light of the social consequences of early childbearing, unplanned pregnancy, and the transmission of AIDS, a great need exists to understand how adolescents make sexual and reproductive decisions. Drawing primarily on literature from sub-Saharan Africa, this article focuses on three behavioral outcomes: nonmarital sexual activity, contraceptive use, and condom use. It explores adolescent's perceptions of the costs and benefits of engaging in these behaviors, their assessment of their susceptibility to the potential consequences of their actions, and the role of family, peer, and dyadic factors in shaping their reproductive decisions. The literature reveals that cultural values regarding sexuality and gender roles, the power dimensions of adolescents' lives, and economic disadvantage exert powerful influences on the decisionmaking process. Decisions to engage in unprotected sex may also be based on insufficient knowledge and distorted judgements of the risks of becoming pregnant and acquiring sexually transmitted infections. Nondecisionmaking is found to be fairly common in some contexts. | pubmed_443_331 |
pubmed_625_4287 | Ras proteins participate in multiple signal cascades, regulating crucial cellular processes, including cell survival, proliferation, and differentiation. We have previously reported that Ras proteins are modified by sumoylation and that Lys-42 plays an important role in mediating the modification. In the current study, we further investigated the role of Lys-42 in regulating cellular activities of K-Ras. Inducible expression of K-RasV12 led to the activation of downstream components, including c-RAF, MEK1, and extracellular signal-regulated kinases (ERKs), whereas expression of K-RasV12/R42 mutant compromised the activation of the RAF/MEK/ERK signaling axis. Expression of K-RasV12/R42 also led to reduced phosphorylation of several other protein kinases, including c-Jun N-terminal kinase (JNK), Chk2, and focal adhesion kinase (FAK). Significantly, K-RasV12/R42 expression inhibited cellular migration and invasion in vitro in multiple cell lines, including transformed pancreatic cells. Given that K-Ras plays a crucial role in mediating oncogenesis in the pancreas, we treated transformed pancreatic cells of both BxPC-3 and MiaPaCa-2 with 2-D08, a small ubiquitin-like modifier (SUMO) E2 inhibitor. Treatment with the compound inhibited cell migration in a concentration-dependent manner, which was correlated with a reduced level of K-Ras sumoylation. Moreover, 2-D08 suppressed expression of ZEB1 (a mesenchymal cell marker) with concomitant induction of ZO-1 (an epithelial cell marker). Combined, our studies strongly suggest that posttranslational modification(s), including sumoylation mediated by Lys-42, plays a crucial role in K-Ras activities in vivo. | 10.1074/jbc.RA118.003723 |
pubmed_326_11611 | Cerebral blood flow (CBF) at rest was measured by 123I-IMP SPECT and the standing test was conducted by 99mTc-HMPAO SEPCT in patients with dementia of Alzheimer's type (DAT) and vascular dementia (VD) in order to evaluate cerebral autoregulation and to consider the diagnostic significance of this determination and test. CBF at rest decreased significantly in all regions in the DAT and VD groups compared to the control groups (healthy aged persons, group C). The value of mean CBF also decreased significantly in the DAT (40.1 micromilligrams/100 g/min) and VD groups (41.3) as compared to group C (51.0). In the DAT groups, the CBF was significantly lower in the parietal region compared to VD groups, and CBF and Hasegawa's dementia score showed a positive correlation in the temporal and parietal regions. Decreases in blood pressure upon standing were about 10 mmHg in all three groups, but the decrease rate in mean CBF was significantly greater in the VD groups (20.2%) than in the C (5.0%) and DAT groups (4.0%). The dysautoregulation index (D.I. delta; % CBF mmHg), used as a measurement of cerebral autoregulation, was significantly higher in the VD groups (1.7) than in the C(0.5) and DAT groups (0.3). This index made it possible to make differential diagnosis in some patients in whom it was impossible using CBF at rest, probably due to impaired cerebral autoregulation and atherosclerotic changes in VD patients. Our findings suggest that D.I. provides information on the condition of patients that cannot be obtained with CBF at rest and assists in differential diagnosis. | 10.3143/geriatrics.33.95 |
pubmed_908_10578 | The LaF3 nanocrystals through a facile hydrothermal route with hexagonal structures have been synthesized via doping of trivalent rare earth (RE3+ ) ions - RE = Tb, Sm, Dy and Tm - with rod-like and perforated morphologies using NH4 F as fluorine precursor. Hexagonal phase formation was confirmed by powder X-ray diffraction. The crystalline sizes were calculated by the Scherrer equation where found to have an average crystalline size of 12 to 35 nm. The morphological studies of the nanocrystals were carried out by means of transmission electron microscopy (TEM). The LaF3 :Tm3+ ,Sm3+ ions show the characteristic emission of Tb3+ and Tm3+ respectively. In Sm3+ -doped LaF3 , three prominent emission peaks at 561, 597 and 641 nm were found, which belong to 4 G5/2 → 6 H5/2 , 4 G5/2 → 6 H7/2 (magnetic dipole) and 4 G5/2 → 6 H9/2 (electric dipole) transitions, respectively. The Dy3+ activated LaF3 shows blue and yellow emission and the corresponding CIE color coordinate show white light emission (CCT value 10650 K). | 10.1002/bio.3488 |
pubmed_165_15662 | Sonographic and CT-guided punctures allow the evaluation of suspected lesions in the head, thorax, abdomen, retroperitoneum and skeletal system. The size of the lesion to be evaluated determines the size and the diameter of the puncture needle. The quantity of the material obtained will be defined by the diameter of the needle, i.e. fine-needle biopsy is more adequate for cytological than for histological evaluation. Strict adherence to the indications and contraindications for puncture and painstaking performance of the procedure go a long why towards minimizing the complications. The advantage of CT-guided puncture, in contrast to an ultrasound-guided procedure, is visualization during the puncture procedure free from overshadowing. This permits punctures of lesions located deep in the thorax or the abdomen which are overshadowed by the lungs, by air in the small or large bowel or by bone structures. Moreover, this technique yields much more information about the tissues and organs surrounding the suspected lesion. This information is much more investigator-related with ultrasound-guided puncture. Therefore, the CT-guided puncture has become mandatory in the evaluation of suspected lesions. Moreover, using the same technique, percutaneous drainage of fluids in the interpleural space, abscesses in organs, hematomas, lymphoceles and urinomas; ablation of metastases; and sympathicolysis can be carried out. CT-guided puncture thus changes from a minimally invasive diagnostic procedure to a minimally invasive therapy. | 10.1007/s001170050128 |
pubmed_125_17670 | Many writers and organizations have postulated that health care facilities and providers may need to implement a "crisis standard of care" to deal with the exigent circumstances associated with the massive influx of patients infected with the novel coronavirus and suffering from COVID-19. There is a relative scarcity of critical resources, such as intensive care unit beds, emergency department beds, ventilators, personal protective equipment, and medications. Facilities can become overwhelmed. A crisis standard of care can act as a guidepost for rationing supplies and care, should that become necessary. However, that is not without danger. Health care facilities and providers should plan carefully and then act with due deliberation in implementing a crisis standard of care to mitigate or prevent future liability. | 10.1002/jhrm.21441 |
pubmed_474_13678 | Many types of trauma may lead to vascular compromise unless treated effectively and promptly. In addition to direct trauma to a major vessel are the crushing injuries, fractures, and burn injuries which give rise to an ischemia-edema cycle and subsequent muscle necrosis and tissue loss. Objective adjuncts to clinical impressions, such as isotope clearance muscle blood flow or the ultrasound Doppler flowmeter are generally not suitable for continuous, uninterrupted monitoring of the degree of vascular compromise. A technique that appears promising in this respect is that of photoplethysmography. This technique uses a small LED infrared emitter/detector array. Blood volume changes in an illuminated vascular bed produce variations in the amount of reflected light sensed by the detector, which after appropriate electronic amplification results in pulsatile blood flow (if present) and its change with time being displayed on the monitor. This technique was used with 25 trauma patients with good results, avoiding unnecessary compartmental decompression in some cases. It has proved to be a simple technique that requires little or no training for interpretation, provides continuous monitoring, is noninvasive and atraumatic in nature, is portable for easy set-up, and is relatively inexpensive. | 10.1016/s0361-1124(79)80373-1 |
pubmed_251_9428 | Analysis of skin biopsy specimens for the presence of adhesion molecules, composition of cellular infiltrates, Ki-67 antigen expression, and examination of serum for interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) levels, wes performed in patients after allogeneic bone marrow transplantation (alloBMT), to study the pathomechanism of acute graft-versus-host disease (aGvHD). It was found that: 1) early hematological recovery constitutes a risk factor for grade IV GvHD, 2) vascular cell adhesion molecule-1 (VCAM-1) is present in the matrix organizing the cells in the bone marrow and in aGvHD infiltrates, 3) HLA DR antigens aberrant expression in epithelial cells, as well as 4) strong expression of Ki-67 is seen in early stages of aGvHD. These immunopathomorfological lesions are cytokine-dependent. High levels of IL-6 and TNF-alpha were found in sera of patients affected with the aGvHD process and infectious complications. An increase of IL-6 in the course of aGvHD is a sign of poor prognosis. These data support the notion that cytokines facilitate the cell accumulation at the site of aGvHD at the beginning of this process and again, at the final stage of the disease, cytokines high levels are associated with the organ damage. | pubmed_251_9428 |
pubmed_893_4565 | Two common wetland plants, Pampas Grass (Cortaderia selloana) and Lucky Bamboo (Dracaena sanderiana), were used in hydroponic cultivation systems for the treatment of simulated high-sulfate wastewaters. Plants in initial experiments at pH 7.0 removed sulfate more efficiently compared to the same experimental conditions at pH 6.0. Results at sulfate concentrations of 50, 200, 300, 600, 900, 1200, 1500 and 3000 mg/L during three consecutive 7-day treatment periods with 1-day rest intervals, showed decreasing trends of both removal efficiencies and uptake rates with increasing sulfate concentrations from the first to the second to the third 7-day treatment periods. Removed sulfate masses per unit dry plant mass, calculated after 23 days, showed highest removal capacity at 600 mg/L sulfate for both plants. A Langmuir-type isotherm best described sulfate uptake capacity of both plants. Kinetic studies showed that compared to pseudo first-order kinetics, pseudo-second order kinetic models slightly better described sulfate uptake rates by both plants. The Elovich kinetic model showed faster rates of attaining equilibrium at low sulfate concentrations for both plants. The dimensionless Elovich model showed that about 80% of sulfate uptake occurred during the first four days' contact time. Application of three 4-day contact times with 2-day rest intervals at high sulfate concentrations resulted in slightly higher uptakes compared to three 7-day contact times with 1-day rest intervals, indicating that pilot-plant scale treatment systems could be sized with shorter contact times and longer rest-intervals. | 10.1016/j.jenvman.2017.11.039 |
pubmed_747_564 | The practicalities of formulating regulatory policy associated with elective abortion often place public health officials at the center of political controversy. Resulting conflicts can inhibit a rational consideration of long-term objectives in implementing a national policy which assures legal accessibility to all who would select abortion as an alternative to term birth. Regulation which uses primarily structural criteria for monitoring and evaluating services tends to de-emphasize the importanc of contraceptive counseling as a component of abortion services. Our process/outcome evaluation of abortion clinics located in Chicago suggests that contraceptive counseling provided at the time of the abortion procedure has a potential long-term impact in terms of reducing the need for elective abortion. We suggest that regulation policy should include process and outcome criteria which support the eventual reduction in need for abortion as a long-range policy goal and suggest key issues for consideration when such a policy is formulated. | 10.1215/03616878-3-1-43 |
pubmed_463_1443 | Traumatic brain injury in elderly patients is a neglected global disease burden. The main cause is fall, followed by motor vehicle accidents. This review article summarizes different aspects of geriatric traumatic brain injury, including epidemiology, pathology, and effects of comorbidities and pre-injury medications such as antiplatelets and anticoagulants. Functional outcome with or without surgical intervention, cognitive outcome, and psychiatric complications are discussed. Animal models are also reviewed in attempt to explain the relationship of aging and outcome, together with advances in stem cell research. Though elderly people in general did fare worse after traumatic brain injury, certain "younger elderly" people, aged 65-75 years, could have a comparable outcome to younger adults after minor to moderate head injury. | 10.1007/s13670-012-0017-2 |
pubmed_492_7547 | This paper considers generalized partially linear models. We propose empirical likelihood based statistics to construct confidence regions for the parametric and nonparametric componenets. The resulting statistics are shown to be asymptotically chi-squared distributed. Finite sample performance of the proposed statistics is assessed by simulation experiments. The proposed methods are applied to a dataset from an AIDS clinical trial. | pubmed_492_7547 |
pubmed_1088_8395 | The evolutionary effects of Southern Hemisphere Pleistocene oceanographic conditions - marked by fluctuations in sea levels and water temperatures, and redirected currents - are poorly understood. The southeastern tip of Australia presents an intriguing model system for studying the biological impacts of palaeoceanography. In particular, contrasting oceanographic conditions that existed on eastern vs. western sides of the Bassian Isthmus during Pleistocene glacial periods allow for natural comparisons between putative refugial vs. re-invading populations. Whereas many western Tasmanian marine taxa were likely eliminated by cold subantarctic water during the last glacial period, eastern Tasmanian populations would have persisted in relatively warm temperatures mediated by the ongoing influence of the East Australian Current (EAC). Here we test for the effects of contrasting palaeoceanographic conditions on endemic bull kelp, Durvillaea potatorum, using DNA sequence analysis (COI; rbcL) of more than 100 individuals from 14 localities in southeastern Australia. Phylogenetic reconstructions reveal a deep (maximum divergence 4.7%) genetic split within D. potatorum, corresponding to the 'eastern' and 'western' geographical regions delimited by the Bassian Isthmus, a vicariant barrier during low Pleistocene sea levels. Concordant with the western region's cold glacial conditions, samples from western Tasmania and western Victoria are genetically monomorphic, suggesting postglacial expansion from a mainland refugium. Eastern samples, in contrast, comprise distinct regional haplogroups, suggesting the species persisted in eastern Tasmania throughout recent glacial periods. The deep east-west divergence seems consistent with earlier reports of morphological differences between 'western' and 'eastern' D. potatorum, and it seems likely that these forms represent reproductively isolated species. | 10.1111/j.1365-294X.2009.04201.x |
pubmed_1066_23818 | BACKGROUND
Evidence is conflicting regarding differential health outcomes in racial and ethnic minorities with cystic fibrosis (CF), a rare genetic disease affecting approximately 28,000 Americans. We performed a cross-sectional analysis of health outcomes in Black/Latinx patients compared with non-Hispanic Caucasian patients cared for in a CF center in New York City. Adult patients enrolled in the CF Foundation Patient Registry at the Columbia University Adult CF Program and seen at least once during 2019 were included. Health metrics were compared between Black/Latinx and non-Hispanic Caucasian patients.
RESULTS
262 patients were eligible. 39 patients (15%) identified as Black/Latinx or non-Hispanic Caucasian. Descriptive statistics are reported with mean (standard deviation). Current age was 35.9 (13.3) years for non-Hispanic Caucasian and 32.0 (9.3) years for Black/Latinx patients (p = 0.087). Age of diagnosis did not differ between groups; 9.56 (15.96) years versus 11.59 (15.8) years for non-Hispanic Caucasian versus Black/Latinx respectively (p = 0.464). Pulmonary function, measured as mean forced expiratory volume in one second (FEV1) was 70.6 (22.5) percent predicted in non-Hispanic Caucasian versus 59.50 (27.9) percent predicted in Black/Latinx patients (p = 0.010). Number of visits to the CF clinic were similar between groups. When controlled for age, gender, co-morbidities, median income, and insurance status, there was a continued association between minority status and lower FEV1.
CONCLUSIONS
Minorities with CF have significantly lower pulmonary function, the major marker of survival, than non-Hispanic Caucasians, even when controlled for a variety of demographic and socioeconomic factors that are known to affect health status in CF. Significant health disparities based on race and ethnicity exist at a single CF center in New York City, despite apparent similarities in access to guideline based care at an accredited CF Center. This data confirms the importance of design of culturally appropriate preventative and management strategies to better understand how to direct interventions to this vulnerable population with a rare disease. | 10.1186/s13023-021-01965-4 |
pubmed_890_3511 | OBJECTIVE
Motor Unit Number Index (MUNIX) is a quantitative neurophysiological measure that provides an index of the number of lower motor neurons supplying a muscle. It reflects the loss of motor neurons in patients with Amyotrophic Lateral Sclerosis (ALS). However, it is unclear whether MUNIX also detects motor unit loss in strong, non-wasted muscles.
METHODS
Three centres measured MUNIX in 49 ALS patients every three months in six different muscles (abductor pollicis brevis, abductor digiti minimi, biceps brachii, tibialis anterior, extensor digitorum brevis, abductor hallucis) on the less affected side. The decline of MUNIX in initially non-wasted, clinically strong muscles (manual muscle testing, MMT grade 5) was analysed before and after onset of weakness.
RESULTS
In 49 subjects, 151 clinically strong muscles developed weakness and were included for analysis. The average monthly relative loss of MUNIX was 5.0% before and 5.6% after onset of weakness. This rate of change was significantly higher compared to ALS functional rating scale (ALSFRS-R) and compound muscle action potential (CMAP) change over 12months prior to the onset of muscle weakness (p=0.024).
CONCLUSION
MUNIX is an electrophysiological marker that detects lower motor neuron loss in ALS, before clinical weakness becomes apparent by manual muscle testing.
SIGNIFICANCE
This makes MUNIX a good biomarker candidate for disease progression and possibly pharmacodynamics responds. | 10.1016/j.clinph.2016.11.026 |
pubmed_888_3383 | Pediatric cardiac transplantation is currently an accepted option for end-stage heart disease and congenital cardiac malformations. This report focuses on the anesthetic perioperative management in 12 yr. From 1988 to 2001 we performed 90 heart transplantations in 88 children, infants and neonates. The pediatric heart transplant program of the children's heart center at our university hospital started in June 1988 with the transplantation of a 2-yr-old boy who was suffering from congenital heart disease. Since then, 88 transplants have been performed. We divided our patients into two groups. Group 1 ranged from 1988 to 1996 and Group 2 from 1997 to 2001. The patient characteristics have not significantly changed over the years in our institution. At the time of transplantation, mean age of the patients was 2.6 +/- 4.3 yr from the period of 1988-1996 and 2.5 +/- 4.1 yr from 1997 to 2001. Since 1988, 90 transplants (Tx) in 88 patients have been performed. Two patients needed re-Tx within 2 days after the initial operation because of primary graft failure. Indications for Tx were congenital heart disease (n = 67) and cardiomyopathy (n = 21). In the subgroup of the patients suffering from congenital heart disease there were 46 with the diagnosis of HLHS, followed by endocardial fibroelastosis (n = 7); the remaining 14 patients had other complex cardiac malformations and some underwent corrective palliative cardiac surgery before Tx. Sixty-three patients were younger than 1 yr of age and only five children were older than 10 yr. Twenty-three percent of the patients on the waiting list died before Tx was possible. The overall survival rate was 79% at 1 yr and 73% at 5 and 10 yr. Infants with HLHS had a lower probability of survival after 5 yr compared with other diagnosis (69% vs. 84%). Until now 21 patients have died after Tx. The duration of anesthesia, time of CPB and the age at the time of surgery decreased over the years. It is always a challenge for the anesthesiologist to treat these patients with pulmonary hypertension as one of the most critical risks in this group of patients. The preventive therapy with vasodilators as well as the availability of mechanical assist devices before and after heart transplantation reduces the effects of transitional pulmonary hypertension and prevents the development of post-operative right heart failure. | 10.1111/j.1399-3046.2004.00155.x |
pubmed_1_15898 | OBJECTIVE
This study aims to study the biological and biomechanical characteristics of the middle cerebral artery (MCA) in aged and estrogen-intervened aged rats, thereby providing biomechanical basis for clinics.
MATERIALS AND METHODS
Thirty 18-month-old Sprague Dawley (SD) rats, 30 18-month-old estrogen-intervened SD rats, and 30 four-month-old SD rats were studied. The estrogen-intervened rats were given estradiol benzoate on the fifth feeding day. Thirty-four days after the feeding, the serum of each rat was obtained. The radioimmunoassay was performed for the content determination of serum E2, ER, malondialdehyde (MDA), and superoxide dismutase (SOD). The tensile test was performed to evaluate the MCA of each rat.
RESULTS
Through the estrogen intervention, the serum contents of E2, ER, SOD, and MDA in old rats were restored to normal levels. The maximum stress, maximum strain, and elastic limit of the MCA in the aged estrogen-intervened rat group were greater than those of the non-intervened aged rat group, with a significant difference (p < 0.05). The elastic modulus in the aged estrogen-intervened rat group was less than that of the non-intervened aged rat group, with a significant difference (p < 0.05).
CONCLUSION
E2 intervention can improve the flexibility, toughness, and compliance of MCA in aged rats. | pubmed_1_15898 |
pubmed_249_20054 | The intravenous use of positive inotropic agents, such as sympathomimetics and phosphodiesterase inhibitors, in heart failure is limited by pro-arrhythmic and positive chronotropic effects. Chronic use of these agents, while eliciting an improvement in the quality of life of patients with advanced heart failure, has been abandoned because of marked increase in mortality when compared to placebo. Nevertheless, patients with advanced heart failure can benefit from long-term positive inotropic support if the therapy can be delivered 'on demand' and in a manner that is both safe and effective. In this review, we will examine the use of a novel, non-stimulatory electrical signal that can acutely modulate left ventricular (LV) contractility in dogs with chronic heart failure in such a way as to elicit a positive inotropic support. Cardiac contractility modulation (CCM) with the Impulse Dynamic(trade mark) signal was examined in dogs with chronic heart failure produced by intracoronary microembolizations. Delivery of the CCM signal from a lead placed in the great coronary vein for periods up to 10 minutes resulted in significant improvements in cardiac output, LV peak+dP/dt, LV fractional area of shortening and LV ejection fraction measured angiographically. Discontinuation of the signal resulted in a return of all functional parameters to baseline values. In cardiomyocytes isolated from dogs with chronic heart failure, application of the CCM signal resulted in improved shortening, rate of change of shortening and rate of change of relengthening suggesting that CCM application is associated with intrinsic improvement of cardiomyocyte function. The improvement in isolated cardiomyocyte function after application of the CCM signal was accompanied by an increase in the peak and integral of the Ca(2+) transient suggesting modulation of calcium cycling by CCM application. In a limited number of normal dogs, intermittent chronic delivery of the CCM signal for up to 7 days showed chronic maintenance of LV functional improvement. In conclusion, pre-clinical results to date with the Impulse Dynamics CCM signal indicate that this non-pharmacologic therapeutic modality can provide short-term positive inotropic support to the failing heart and as such, may be a useful adjunct in the treatment of advanced heart failure. Additional, long-term studies in dogs with heart failure are needed to establish the safety and efficacy of this therapeutic modality for the chronic treatment of this disease syndrome. | 10.1023/a:1009855208097 |
pubmed_315_18614 | PURPOSE
Before now oral vinorelbine has not yet been tested in a cohort of elderly, advanced non-small cell lung cancer patients, even though the intravenous form of this drug provides a reasonable therapeutic option for this group. This trial was conducted to determine the tumor response rate and toxicity profile of oral vinorelbine in advanced non-small cell lung cancer patients > or = 65 years of age.
PATIENT AND METHODS
Fifty-eight evaluable patients > or = 65 years of age with advanced non-small cell lung cancer were enrolled. Median age was 73 years (range: 65-87). The Eastern Cooperative Oncology Group (ECOG) performance score was 0, 1, or 2 in 29, 59, and 12% of patients, respectively. All patients had adequate organ function. Oral vinorelbine 60 mg/m2 per week was prescribed weekly as first-line therapy.
RESULTS
Two patients manifested a confirmed tumor response, yielding a response rate of 3.4% (95% confidence interval (CI): 0.4, 11.9%). There were no complete responses. Median progression-free survival was 3.5 months (95% CI: 2.2, 5.4 months), and median overall survival was 7.5 months (95% CI: 5.0, 12 months). There were five deaths, one of which might have been treatment-related, and there were 10 grade 4 events.
CONCLUSIONS
Oral vinorelbine, as prescribed in this trial, provides minimal activity in the treatment of advanced non-small cell lung cancer in patients > or = 65 years of age. | 10.1016/j.lungcan.2003.09.012 |
pubmed_743_8690 | Personalized regenerative medicine and biomedical research have been galvanized and revolutionized by human pluripotent stem cells in combination with recent advances in genomics, artificial intelligence, and genome engineering. More recently, we have witnessed the unprecedented breakthrough life-saving translation of mRNA-based vaccines for COVID-19 to contain the global pandemic and the investment in billions of US dollars in space exploration projects and the blooming space-tourism industry fueled by the latest reusable space vessels. Now, it is time to examine where the translation of pluripotent stem cell research stands currently, which has been touted for more than the last two decades to cure and treat millions of patients with severe debilitating degenerative diseases and tissue injuries. This review attempts to highlight the accomplishments of pluripotent stem cell research together with cutting-edge genomics and genome editing tools and, also, the promises that have still not been transformed into clinical applications, with cardiovascular research as a case example. This review also brings to our attention the scientific and socioeconomic challenges that need to be effectively addressed to see the full potential of pluripotent stem cells at the clinical bedside. | 10.3390/cells10113112 |
pubmed_111_2319 | Double-stranded DNA (dsDNA) induces the transfer of phosphate from ATP to several proteins in extracts of widely divergent eukaryotic cells. Extracts of HeLa cells, rabbit reticulocytes, Xenopus eggs and Arbacia eggs all show dsDNA-dependent protein phosphorylation. The mechanism is specific for dsDNA and will not respond to either RNA or single-stranded DNA. One of the proteins which is phosphorylated in response to dsDNA has a subunit mol. wt. of 90 000 and has been identified as a heat-shock protein (hsp90). Although mouse cell extracts were shown to contain hsp90, they failed to show a dsDNA-dependent protein phosphorylation. The observation that dsDNA can modulate the phosphorylation of a set of proteins raises the possibility that dsDNA may play a role as a cellular regulatory signal. | 10.1002/j.1460-2075.1985.tb02328.x |
pubmed_533_14440 | In countries where poliomyelitis has been eradicated, Guillain-Barré syndrome (GBS) is the leading cause of acute flaccid paralysis. The range of infections that precede GBS in Brazil is unknown. Campylobacter jejuni infection is the most frequent trigger of GBS worldwide. Given the lack of systematic surveillance of diarrheal diseases, particularly in adults, the incidence of enteritis caused by C. jejuni in developing countries is unknown. From 2014 to 2016, pretreatment serum samples from 63 GBS patients were tested by immunoglobulin M (IgM) enzyme-linked immunosorbent assay for C. jejuni. Campylobacter jejuni IgM antibodies were detected in 17% (11/63) of the samples. There was no association between serological positivity (IgM) for C. jejuni and the occurrence of diarrhea among the investigated cases (P = 0.36). Hygiene measures, basic sanitation, and precautions during handling and preparation of food of animal origin may help prevent acute flaccid paralysis. | 10.4269/ajtmh.17-0666 |
pubmed_71_13684 | OBJECTIVE
The study involved the synthesis of a novel derivative of caprylic acid - isosorbide dicaprylate (IDC) - and the evaluation of its potential in improving water homoeostasis and epidermal barrier function in human skin.
METHODS
The effect of IDC on gene expression was assayed in skin organotypic cultures by DNA microarrays. The results were then confirmed for a few key genes by quantitative PCR, immuno- and cytochemistry. Final validation of skin hydration properties was obtained by four separate clinical studies. Level of hydration was measured by corneometer either by using 2% IDC lotion alone vs placebo or in combination with 2% glycerol lotion vs 2% glycerol only. A direct comparison in skin hydration between 2% IDC and 2% glycerol lotions was also carried out. The epidermal barrier function improvement was assessed by determining changes in transepidermal water loss (TEWL) on the arms before and after treatment with 2% IDC lotion versus placebo.
RESULTS
IDC was found to upregulate the expression of AQP3, CD44 and proteins involved in keratinocyte differentiation as well as the formation and function of stratum corneum. A direct comparison between 2% IDC versus 2% glycerol lotions revealed a three-fold advantage of IDC in providing skin hydration. Severely dry skin treated with 2% IDC in combination with 2% glycerol showed 133% improvement, whereas 35% improvement was observed with moderately dry human skin.
CONCLUSION
Topical isosorbide dicaprylate favourably modulates genes involved in the maintenance of skin structure and function, resulting in superior clinical outcomes. By improving skin hydration and epidermal permeability barrier, it offers therapeutic applications in skin ageing. | 10.1111/ics.12405 |
pubmed_320_137 | In the report "Single-crystal (40)Ar/(39)Ar dating of the Eocene-Oligocene transition in North America" (17 Aug., p. 760), the affiliation of first author Carl C. Swisher III should have been given as the Institute of Human Origins Geochronology Center, 2453 Ridge Road, Berkeley, CA 94709. | 10.1126/science.494-b |
pubmed_466_14480 | Damage to the central and peripheral nervous system often produces lasting functional deficits. A major focus of neuroscience research has been to enhance functional restitution of the damaged nervous system and thereby produce recovery of behavioral or physiological processes. Promising procedures include surgical, physical, and chemical manipulations to reduce scar formation and minimize the disruption of support elements, administration of growth-stimulating substances, tissue grafts to bridge gaps in fiber pathways, and embryonic brain tissue grafts to provide new cells with the potential to generate fiber systems. Two elements are required for functional nervous system repair: (i) neurons with the capacity to extend processes must be present, and (ii) the regenerating neurites must find a continuous, unbroken pathway to appropriate targets through a supportive milieu. | 10.1126/science.3975624 |
pubmed_480_22083 | Human voices consist of specific patterns of acoustic features that are considerably enhanced during affective vocalizations. These acoustic features are presumably used by listeners to accurately discriminate between acoustically or emotionally similar vocalizations. Here we used high-field 7T functional magnetic resonance imaging in human listeners together with a so-called experimental 'feature elimination approach' to investigate neural decoding of three important voice features of two affective valence categories (i.e. aggressive and joyful vocalizations). We found a valence-dependent sensitivity to vocal pitch (f0) dynamics and to spectral high-frequency cues already at the level of the auditory thalamus. Furthermore, pitch dynamics and harmonics-to-noise ratio (HNR) showed overlapping, but again valence-dependent sensitivity in tonotopic cortical fields during the neural decoding of aggressive and joyful vocalizations, respectively. For joyful vocalizations we also revealed sensitivity in the inferior frontal cortex (IFC) to the HNR and pitch dynamics. The data thus indicate that several auditory regions were sensitive to multiple, rather than single, discriminative voice features. Furthermore, some regions partly showed a valence-dependent hypersensitivity to certain features, such as pitch dynamic sensitivity in core auditory regions and in the IFC for aggressive vocalizations, and sensitivity to high-frequency cues in auditory belt and parabelt regions for joyful vocalizations. | 10.1093/scan/nsw066 |
pubmed_1028_1256 | A simple method of comparing and/or monitoring the radiation output level of a Computed Tomography (CT) system, using a specially developed pencil-shaped ionization chamber, is presented. When the measurement is made with a phantom for the period of one tomographic scan, the result can be interpreted as the average exposure along the chamber axis resulting from the entire series of scans to be performed by the CT system. An interesting feature of this method is that no detailed knowledge of the beam distribution or slice thickness is necessary in order to measure the radiation output level, to compare the performance of CT systems or the estimate patient's exposure for a particular combination of CT operation parameters. | 10.1118/1.594445 |
pubmed_192_4095 | Neuropathic pain sometimes occurs during chemotherapy with paclitaxel or HIV/AIDS antiretroviral therapy with nucleoside reverse transcriptase inhibitors (NRTIs). We previously reported that coadministration of indomethacin plus minocycline (IPM) was antihyperalgesic in a cannabinoid type 1 (CB1) receptor-dependent manner in a mouse model of paclitaxel-induced neuropathic pain. We evaluated if IPM combination has antihyperalgesic and antiallodynic activities in animal models of paclitaxel or NRTI (ddC, zalcitabine)-induced neuropathic pain, and whether antagonists of CB1, CB2 receptors or G protein-coupled receptor 55 (GPR55) can inhibit these activities of IPM. IPM produced antihyperalgesic and antiallodynic effects against paclitaxel and ddC-induced thermal hyperalgesia and mechanical allodynia. WIN 55,212-2, a cannabinoid receptor agonist, also had antihyperalgesic activity. The antihyperalgesic and antiallodynic activities of IPM were antagonized by a CB1 receptor antagonist AM251 and a CB2 receptor antagonist AM630, but not a GPR55 antagonist ML193. IPM had no effects on the mean time spent on the rotarod, whereas WIN 55,212-2 reduced it in a dose-dependent manner. These results show that IPM at a fixed ratio produces antihyperalgesic and antiallodynic effects in mice models of both paclitaxel and NRTI-induced neuropathic pain which is dependent on both CB1 and CB2 receptors, without causing the typical cannabinoid receptor agonist-induced motor impairment. | 10.1016/j.jphs.2019.02.007 |
pubmed_100_7902 | The aim of this study was to investigate the effect of transient global brain ischaemia, both naïve and preconditioned, on accumulation of ubiquitinylated proteins and induction of stress/chaperone proteins specific to cytoplasm and endoplasmic reticulum. In addition, possible correlation between stress response and ischaemia/induced translocation of p53 to mitochondria was investigated. Rats were subjected to 15-min forebrain ischaemia followed by 1, 3, 24 and 72 h of reperfusion. Transient cerebral ischaemia induced a massive increase in protein ubiquitinylation in the hippocampus as well as in both cerebral and cerebellar cortex. Enhanced ubiquitinylation of proteins was paralleled with transcriptional activation of hsp70.1 gene but not hsp70.3 gene. However, HSP70 protein level was significantly elevated 24 and 72 h after ischaemia. Neither ischaemia nor ischaemia followed by reperfusion was associated with significant changes of GRP78, GADD34 and GADD153 levels. Ubiquitinylated protein level was elevated 1 and 48 h after sub-lethal 5 min ischaemia. Preconditioned ischaemia (15 min ischaemia followed 48 h after sub-lethal ischaemia) was associated with even enhanced accumulation of ubiquitinylated proteins of molecular mass higher than 110 kDa. HSP70 protein was significantly elevated 48 h after sub-lethal ischaemia as well as after preconditioned ischaemia and all investigated time intervals of reperfusion. The elevated level of HSP70 might represent plausible explanation of inhibition of both translocation of p53 to mitochondria and ischaemia-induced apoptosis observed after preconditioned ischaemia. | 10.1007/s10571-011-9740-z |
pubmed_633_4465 | OBJECTIVE
To assess the morbidity and mortality associated with extensive upper abdominal surgery (EUAS) performed during primary cytoreduction for advanced ovarian carcinoma.
METHODS
We identified all patients who underwent EUAS during primary cytoreduction for advanced ovarian, tubal, or peritoneal cancer at our institution from 1/01 to 12/06. Major grade 3-5 complications were those that led to invasive radiologic intervention, re-operation, unplanned ICU admission, chronic disability, or death within 30 days of surgery.
RESULTS
There were 141 eligible patients, with a median age of 60 years (range, 38-82). The majority of patients had stage IIIC disease, 103 (73%); serous histology, 131 (93%); and ascites, 118 (84%). There were 229 EUAS procedures performed-diaphragm peritonectomy, 101 (72%); splenectomy, 45 (32%); full-thickness diaphragm resection, 19 (14%); partial hepatectomy, 18 (13%); distal pancreatectomy, 17 (12%); cholecystectomy, 15 (11%); and resection of porta hepatis tumor, 14 (10%). Cytoreductive outcomes were: no gross residual, 42 (30%); residual ≤ 1cm, 85 (60%); and residual >1cm, 14 (10%). Grade 3-5 complications occurred in 31 (22%) patients, including 2 mortalities (1.4%). In 21/31 (68%), the complication was successfully managed with percutaneous drainage of infected or non-infected collections. Overall median survival for all patients was 57 months.
CONCLUSIONS
Rates of major morbidity and mortality following EUAS for primary cytoreduction were 22% and 1.4%, respectively. Approximately two-thirds of complications were readily managed by percutaneous drainage of collections. With an overall median survival of 57 months in a cohort of patients with a large tumor burden, this rate of morbidity and mortality appears acceptable. | 10.1016/j.ygyno.2010.05.031 |
pubmed_936_507 | Acute and chronic alcohol use is associated with injury, and autopsies may be performed to ascertain injury deaths in persons with acute or chronic alcohol use. This study sought to determine how many decedents with a history of acute or chronic alcohol use had an internal physical injury diagnosed only at autopsy that caused or contributed to the death. The study reviewed medicolegal investigation and autopsy reports at the New York City Office of Chief Medical Examiner between January 1 and October 11, 2018, to identify 1000 consecutive persons with suspected acute or chronic alcohol use who were autopsied to ascertain whether internal physical injury caused or contributed to the death. Of 1000 persons with known or suspected acute or chronic alcohol use, 390 (39.0%) had an external injury. Although 115 (11.5%) had an internal injury at autopsy, only 29 (2.9%) had an injury that caused or contributed to the death. Only 1 decedent had an internal injury that caused the death with no associated external evidence of injury (0.1%). This study demonstrates the rarity of occult lethal injury diagnosed at autopsy in persons with acute or chronic alcohol use. | 10.1097/PAF.0000000000000765 |
pubmed_294_16942 | A deviation from the hydroxyapatite hexagonal symmetry of a human tooth enamel crystal observed by high-resolution electron microscopy is reported. This symmetry deviation is characterized by: (1) 'preferential' planes that can be indexed as (100) with an intensity that differs from the (300) and the other (100) hexagonal equivalent planes; and (2) streaking of higher order reflections in the optical diffractogram of the image of the crystal. Computer simulations show that similar 'preferential' planes can also be observed at specific crystal tilt angles (and/or beam tilt and/or objective aperture misalignment) and at crystal thickness/microscope defocus values in images of hydroxyapatite crystals observed along the [0001] or [2243] zone axes. The streaking of higher order reflections in the optical diffractogram is related to a deformation of the crystal itself and does indeed show a symmetry deviation of the crystal under observation. | 10.1111/j.1365-2818.1993.tb03334.x |
pubmed_1032_14919 | OBJECTIVE
The tinnitus functional index (TFI), a new self-report questionnaire, was developed for the measurement of tinnitus severity and treatment-related changes. The original English version has been translated into several languages. The aim of this study was to evaluate the reliability and validity of the Japanese version of the TFI.
DESIGN
The English version of the TFI was translated into Japanese using a translation-back translation method. Participants completed a series of questionnaires including the TFI, Tinnitus Handicap Inventory (THI), Self-rating Depression Scale, State-Trait Anxiety Inventory, Visual Analogue Scale, and the questionnaire of subjective symptom improvement. We examined internal consistency, reproducibility, convergent and discriminant validity, and effect sizes.
STUDY SAMPLE
One hundred and forty-three patients with subjective tinnitus were included.
RESULTS
The Japanese version of the TFI had high internal consistency and reproducibility, and good convergent and discriminant validity. At six months after the start of treatment, the effect sizes for the TFI were somewhat larger than those for the THI.
CONCLUSIONS
The Japanese version of the TFI is appropriate for measuring tinnitus severity and treatment-related changes. The reliability and validity of this version are comparable to those of the original English version of the TFI. | 10.1080/14992027.2018.1534279 |
pubmed_824_24583 | Childhood trauma is common among survivors and perpetrators of intimate partner violence (IPV). Although symptoms of posttraumatic stress disorder (PTSD) and dissociative disorders (DDs) are predictors of IPV victimization and perpetration, few studies explore IPV among those with DDs. The present study examined IPV and symptoms as predictors among participants in the Treatment of Patients With Dissociative Disorders (TOP DD) Network study, an educational intervention for individuals with DDs and their clinicians. Both clinicians and patients reported on patients' history of physical, emotional, and sexual IPV as both victims and perpetrators. Patients self-reported dissociative, posttraumatic (PTSD), and emotion dysregulation symptoms, as well as IPV-specific dissociative symptoms. According to patients and clinicians, patients were frequently victims of IPV, most commonly emotional IPV. Dissociative symptoms predicted IPV exposure, whereas dissociative and emotion dysregulation symptoms predicted IPV-specific dissociative symptoms. | 10.1177/0886260517746943 |
pubmed_98_25757 | The long-term behavior of a modulationally unstable conservative nonintegrable system is known to be characterized by the soliton turbulence self-organization process. We consider this problem in the presence of a long-range interaction in the framework of the Schrödinger-Poisson (or Newton-Schrödinger) equation accounting for the gravitational interaction. By increasing the amount of nonlinearity, the system self-organizes into a large-scale incoherent localized structure that contains "hidden" coherent soliton states: The solitons can hardly be identified in the usual spatial or spectral domains, but their existence can be unveiled in the phase-space representation (spectrogram). We develop a theoretical approach that provides the coupled description of the coherent soliton component [governed by the Schrödinger-Poisson equation (SPE)] and of the incoherent structure [governed by a wave turbulence Vlasov-Poisson equation (WT-VPE)]. We demonstrate theoretically and numerically that the incoherent structure introduces an effective trapping potential that stabilizes the hidden coherent soliton and we show that the incoherent structure belongs to a family of stationary solutions of the WT-VPE. The analysis reveals that the incoherent structure evolves in the strongly nonlinear regime and that it is characterized by a compactly supported spectral shape. By relating the analytical properties of the hidden soliton to those of the stationary incoherent structure, we clarify the quantum-to-classical (i.e., SPE-to-VPE) correspondence in the limit ℏ/m→0: The hidden soliton appears as the latest residual quantum correction preceding the classical limit described by the VPE. This study is of potential interest for self-gravitating Boson models of fuzzy dark matter. Although we focus our paper on the Schrödinger-Poisson equation, we show that the regime of hidden solitons stabilized by an incoherent structure is general for long-range wave systems featured by an algebraic decay of the interacting potential. This work should stimulate nonlinear optics experiments in highly nonlocal nonlinear (thermal) media that mimic the long-range nature of gravitational interactions. | 10.1103/PhysRevE.104.054205 |
pubmed_526_7584 | The congenital myasthenic syndromes (CMS) are a diverse group of genetic disorders caused by abnormal signal transmission at the motor endplate, a special synaptic contact between motor axons and each skeletal muscle fibre. Most CMS stem from molecular defects in the muscle nicotinic acetylcholine receptor, but they can also be caused by mutations in presynaptic proteins, mutations in proteins associated with the synaptic basal lamina, defects in endplate development and maintenance, or defects in protein glycosylation. The specific diagnosis of some CMS can sometimes be reached by phenotypic clues pointing to the mutated gene. In the absence of such clues, exome sequencing is a useful technique for finding the disease gene. Greater understanding of the mechanisms of CMS have been obtained from structural and electrophysiological studies of the endplate, and from biochemical studies. Present therapies for the CMS include cholinergic agonists, long-lived open-channel blockers of the acetylcholine receptor ion channel, and adrenergic agonists. Although most CMS are treatable, caution should be exercised as some drugs that are beneficial in one syndrome can be detrimental in another. | pubmed_526_7584 |
pubmed_603_3502 | Limonene has a strong tendency to form secondary organic aerosol (SOA) in the atmosphere and in indoor environments. Initial oxidation occurs mainly via ozone or OH radical chemistry. We studied the effect of O(3) concentrations with or without a OH radical scavenger (2-butanol) on the SOA mass and thermal characteristics using the Gothenburg Flow Reactor for Oxidation Studies at Low Temperatures and a volatility tandem differential mobility analyzer. The SOA mass using 15 ppb limonene was strongly dependent on O(3) concentrations and the presence of a scavenger. The SOA volatility in the presence of a scavenger decreased with increasing levels of O(3), whereas without a scavenger, there was no significant change. A chemical kinetic model was developed to simulate the observations using vapor pressure estimates for compounds that potentially contributed to SOA. The model showed that the product distribution was affected by changes in both OH and ozone concentrations, which partly explained the observed changes in volatility, but was strongly dependent on accurate vapor pressure estimation methods. The model-experiment comparison indicated a need to consider organic peroxides as important SOA constituents. The experimental findings could be explained by secondary condensed-phase ozone chemistry, which competes with OH radicals for the oxidation of primary unsaturated products. | 10.1021/es301750r |
pubmed_947_13146 | IMPORTANCE
The impact of the SARS-CoV-2 pandemic on children remains unclear. Better understanding of the burden of COVID-19 among children and their protection against re-infection is crucial as they will be among the last groups vaccinated.
OBJECTIVE
To characterize the burden of COVID-19 and assess how protection from symptomatic re-infection among children may vary by age.
DESIGN
A prospective, community-based pediatric cohort study conducted from March 1, 2020 through October 15, 2021.
SETTING
The Nicaraguan Pediatric Influenza Cohort is a community-based cohort in District 2 of Managua, Nicaragua.
PARTICIPANTS
A total of 1964 children aged 0-14 years participated in the cohort. Non-immunocompromised children were enrolled by random selection from a previous pediatric influenza cohort. Additional newborn infants aged ≤4 weeks were randomly selected and enrolled monthly, via home visits.
EXPOSURES
Prior COVID-19 infection as confirmed by positive anti SARS-CoV-2 antibodies (receptor binding domain [RBD] and spike protein) or real time RT-PCR confirmed COVID-19 infection ≥60 days prior to current COVID-19.
MAIN OUTCOMES AND MEASURES
Symptomatic COVID-19 cases confirmed by real time RT-PCR and hospitalization within 28 days of symptom onset of confirmed COVID-19 case.
RESULTS
Overall, 49.8% of children tested were seropositive over the course of the study. There were also 207 PCR-confirmed COVID-19 cases, 12 (6.4%) of which were severe enough to require hospitalization. Incidence of COVID-19 was highest among children aged <2 years-16.1 per 100 person-years (95% Confidence Interval [CI]: 12.5, 20.5)-approximately three times that of children in any other age group assessed. Additionally, 41 (19.8%) symptomatic SARS-CoV-2 episodes were re-infections, with younger children slightly more protected against symptomatic reinfection. Among children aged 6-59 months, protection was 61% (Rate Ratio [RR]:0.39, 95% CI:0.2,0.8), while protection among children aged 5-9 and 10-14 years was 64% (RR:0.36,0.2,0.7), and 49% (RR:0.51,0.3-0.9), respectively.
CONCLUSIONS AND RELEVANCE
In this prospective community-based pediatric cohort rates of symptomatic and severe COVID-19 were highest among the youngest participants, with rates stabilizing around age 5. Reinfections represent a large proportion of PCR-positive cases, with children <10 years displaying greater protection from symptomatic reinfection. A vaccine for children <5 years is urgently needed.
KEY POINTS
Question: What is the burden of COVID-19 among young children and how does protection from re-infection vary with age?Findings: In this study of 1964 children aged 0-14 years children <5 years had the highest rates of symptomatic and severe COVID-19 while also displaying greater protection against re-infection compared to children ≥10 years.Meaning: Given their greater risk of infection and severe disease compared to older children, effective vaccines against COVID-19 are urgently needed for children under 5. | 10.1101/2022.01.03.22268684 |
pubmed_730_1393 | A new in vivo test for burst strength of arterial anastomoses was tested in 40 rats. Twelve had a severed right femoral artery reanastomosed by the traditional nine-suture technique. In a second group of 12, a modified telescoping sleeve method of reanastomosis was used. In a third group of 12, a laser-assisted anastomosis using four stay sutures was performed. Four rats had sham procedures. Immediately after reanastomosis three vessels from each group plus all four sham surgical vessels were subjected to burst testing. These tests were performed again on the repaired vessels at 1 week, 1 month, and 2 months. All the vessels were patent at burst testing. All repairs held at all times to greater than 160 mm mean arterial pressure. The four-suture telescopic anastomosis technique was consistently strongest over time, but all techniques showed adequate strength at all time intervals. | 10.1002/(sici)1098-2752(1998)18:1<29::aid-micr7>3.0.co;2-p |
pubmed_1003_15056 | New approaches to antibiotic design are desperately needed. The design of simple oligomers that capture the shape and biological function of natural antimicrobial peptides could prove to be versatile and highly successful. We discuss the use of aromatic backbones to design facially amphiphilic (FA) beta-sheet like structures which are potently antimicrobial. These oligomers capture the physiochemical properties of peptides like the Magainins and Defensins, which fold into specific conformations that are amphiphilic resulting in antimicrobial activity. However, natural peptides are expensive to prepare and difficult to produce on large scale. The design of polymers and oligomers that mimic the complex structures and remarkable biological properties of proteins is an important endeavor and provides attractive alternatives to the difficult synthesis of natural peptides. We therefore have designed a series of FA oligomers that are easy to prepare from inexpensive monomers. They adopt structures very reminiscent of amphiphilic beta-sheets and have significant activity with minimal inhibitory concentrations at 6 h in the low microgram per ml range (muM to nM). They are active against a broad spectrum of bacteria including gram-positive and gram-negative as well as antibiotic resistant strains. | 10.1007/s10295-005-0219-0 |
pubmed_447_1518 | The aim of the present study was to correlate the gastric emptying (GE) of nondisintegrating tablets with changes in gastrointestinal (GI) motility. Eight, healthy, male subjects each received 5 x 7-mm radiolabeled tablets, a radiolabeled meal, and a radiotelemetry capsule (RTC). Transit of the radiolabeled formulations was followed by gamma scintigraphy and the RTC detected contractile activity in the GI tract. The study demonstrated that 7-mm tablets can empty from the fed stomach, prior to the onset of interdigestive activity. Those tablets that were not emptied during fed activity were retained through the period of quiescence associated with the onset of the migrating myoelectric complex (MMC) and left the stomach during contractions associated with phase 2 and 3 activity. The RTC was retained in the stomach and was emptied only by large phase 3 contractions commonly termed the "housekeeper" wave. However, in one subject, the RTC was retained in the stomach for over 12 hr, during which time three distinct phase 3 complexes were monitored. | 10.1023/a:1015855829864 |
pubmed_391_6770 | Recent studies suggest that one or more genes on chromosome 5q21 are important for the development of colorectal cancers, particularly those associated with familial adenomatous polyposis (FAP). To facilitate the identification of genes from this locus, a portion of the region that is tightly linked to FAP was cloned. Six contiguous stretches of sequence (contigs) containing approximately 5.5 Mb of DNA were isolated. Subclones from these contigs were used to identify and position six genes, all of which were expressed in normal colonic mucosa. Two of these genes (APC and MCC) are likely to contribute to colorectal tumorigenesis. The MCC gene had previously been identified by virtue of its mutation in human colorectal tumors. The APC gene was identified in a contig initiated from the MCC gene and was found to encode an unusually large protein. These two closely spaced genes encode proteins predicted to contain coiled-coil regions. Both genes were also expressed in a wide variety of tissues. Further studies of MCC and APC and their potential interaction should prove useful for understanding colorectal neoplasia. | 10.1126/science.1651562 |
pubmed_269_14887 | Genome-wide association studies (GWASs) of Huntington disease (HD) have identified six DNA maintenance gene loci (among others) as modifiers and implicated a two step-mechanism of pathogenesis: somatic instability of the causative HTT CAG repeat with subsequent triggering of neuronal damage. The largest studies have been limited to HD individuals with a rater-estimated age at motor onset. To capitalize on the wealth of phenotypic data in several large HD natural history studies, we have performed algorithmic prediction by using common motor and cognitive measures to predict age at other disease landmarks as additional phenotypes for GWASs. Combined with imputation with the Trans-Omics for Precision Medicine reference panel, predictions using integrated measures provided objective landmark phenotypes with greater power to detect most modifier loci. Importantly, substantial differences in the relative modifier signal across loci, highlighted by comparing common modifiers at MSH3 and FAN1, revealed that individual modifier effects can act preferentially in the motor or cognitive domains. Individual components of the DNA maintenance modifier mechanisms may therefore act differentially on the neuronal circuits underlying the corresponding clinical measures. In addition, we identified additional modifier effects at the PMS1 and PMS2 loci and implicated a potential second locus on chromosome 7. These findings indicate that broadened discovery and characterization of HD genetic modifiers based on additional quantitative or qualitative phenotypes offers not only the promise of in-human validated therapeutic targets but also a route to dissecting the mechanisms and cell types involved in both the somatic instability and toxicity components of HD pathogenesis. | 10.1016/j.ajhg.2022.03.004 |
pubmed_569_4801 | Psychopathology as the investigation and classification of experience, behavior and symptoms in psychiatric patients is an old discipline that ranges back to the end of the 19th century. Since then different approaches to psychopathology have been suggested. Recent investigations showing abnormalities in the brain on different levels raise the question how the gap between brain and psyche, between neural abnormalities and alteration in experience and behavior can be bridged. Historical approaches like descriptive (Jaspers) and structural (Minkoswki) psychopathology as well as the more current phenomenological psychopathology (Paarnas, Fuchs, Sass, Stanghellini) remain on the side of the psyche giving detailed description of the phenomenal level of experience while leaving open the link to the brain. In contrast, the recently introduced Research Domain Classification (RDoC) aims at explicitly linking brain and psyche by starting from so-called 'neuro-behavioral constructs'. How does Spatiotemporal Psychopathology, as demonstrated in the first paper on depression, stand in relation to these approaches? In a nutshell, Spatiotemporal Psychopathology aims to bridge the gap between brain and psyche. Specifically, as demonstrated in depression in the first paper, the focus is on the spatiotemporal features of the brain's intrinsic activity and how they are transformed into corresponding spatiotemporal features in experience on the phenomenal level and behavioral changes, which can well account for the symptoms in these patients. This second paper focuses on some of the theoretical background assumptions in Spatiotemporal Psychopathology by directly comparing it to descriptive, structural, and phenomenological psychopathology as well as to RDoC. | 10.1016/j.jad.2015.05.008 |
pubmed_1012_8116 | In a chemically defined serum-free medium, insulin can stimulate DNA synthesis of the mouse mammary tumor-derived cell line GR2H6 up to 3 - 5 fold above the control group as measured by (3)H-thymidine incorporation. By growing GR2H6 cells in the 24-well and 96-well plates, a bioassay system for the growth promoting activity of insulin has been established. This method has the advantages such as easy operation, less time-consuming and suitable for measuring a large number of samples simultaneously. It may provide a novel model system for studies on the relationships between the growth promoting activity and the structure of insulin. | pubmed_1012_8116 |
pubmed_1131_1951 | BVA has produced a briefing paper on the possible implications of a British exit from the EU and is inviting vets to have their say via the BVA community, explains BVA policy offer Susie Child. | 10.1136/vr.i3111 |
pubmed_322_13230 | Simmitecan is a new ester anticancer prodrug which can exert the antiproliferation activity through its active metabolite, chimmitecan. In the current study, a simple and reliable liquid chromatography-tandem mass spectrometry method was developed and validated for simultaneous determination of simmitecan and chimmitecan in human plasma. Both irinotecan and 7-ethyl-10-hydroxycamptothecin were used as the internal standards. Plasma samples were protein precipitated by acetonitrile (0.2% formic acid, v/v) and processed samples were chromatographed on a Hypersil GOLDTM C18 column (100 × 4.6 mm, i.d. 3.0 μm) with acetonitrile and 10 mM ammonium acetate (0.1% formic acid, v/v) as the mobile phase. The calibration curves showed good linearity (R ≥ 0.99) over the concentration range of 1-500 ng/mL and 0.25-125 ng/mL for simmitecan and chimmitecan, respectively. Intra- and inter-run precisions (CV%) were ≤10.2% for simmitecan and ≤12.1% for chimmitecan. The accuracies were 99.4-103.5% for simmitecan and 95.4-103.5% for chimmitecan. This method was further successfully applied to a pharmacokinetic study of simmitecan in Chinese advanced solid cancer patients after administration of simmitecan hydrochloride injection. | 10.1002/jssc.202100491 |
pubmed_191_8097 | During early pregnancy, a "critical period" may be defined between Days 15 and 17. Embryonic mortality associated with this period causes significant economic losses to the cattle industry. During this period, the endometrium will follow a default program to release luteolytic pulses of PGF2alpha, unless the conceptus sends appropriate antiluteolytic signals to block PGF2alpha, production. Maintenance of pregnancy is dependent on a successful blockage of endometrial PGF2alpha production. Biology of the critical period is complex and multifactorial. Endocrine, cellular and molecular factors, both from maternal and conceptus origins act in concert to determine whether luteolysis or maintenance of pregnancy will prevail. Understanding the influences of such factors in the biology of the critical period allowed researchers to produce a series of strategies aiming to favor maintenance of pregnancy in lieu of luteolysis. Strategies include hormonal and nutritional manipulations to decrease plasma concentrations of estradiol 17beta (E2) while increasing those of progesterone (P4), and inhibiting the PGF2alpha-synthesizing enzymatic machinery in the endometrium during the critical period. Experimental results indicate that use of such strategies has improved pregnancy rates following artificial insemination and embryo transfer programs. | 10.1016/s0093-691x(01)00646-x |
pubmed_87_18937 | Potassium iodide (KI) is recommended as an emergency treatment for exposure to radioiodines, most commonly associated with nuclear detonation or mishaps at nuclear power plants. Protecting the thyroid gland of infants and children remains a priority because of increased incidence of thyroid cancer in the young exposed to radioiodines (such as (131)I and (133)I). There is a lack of clinical studies for KI and radioiodines in children or infants to draw definitive conclusions about the effectiveness and safety of KI administration in the young. In this paper, we compare functional aspects of the hypothalamic-pituitary-thyroid (HPT) axis in the young and adults and review the limited studies of KI in children. The HPT axis in the infant and child is hyperactive and therefore will respond less effectively to KI treatment compared to adults. Research on the safety and efficacy of KI in infants and children is needed. | 10.1155/2014/710178 |
pubmed_962_21510 | A 9-week in vivo rasH2/butylhydroxytoluene (BHT) model for the detection of genotoxic lung carcinogens was validated, using six potent positive test compounds, dimethylnitrosamine (DMN; 15 mg/kg, i.p.), diethylnitrosamine (DEN; 100 mg/kg, i.p.), ethylnitrosourea (ENU; 120 mg/kg, i.p.), 3-methylcholanthrene (MC; 100 mg/kg, i.p.), 7,12-dimethylbenz(a)anthracene (DMBA; 5 mg/kg, i.g.) and benzo(a)pyrene (B(a)P; 80 mg/kg, i.p.), each given to rasH2 mice of both genders by single administration for initiation followed by promoter BHT treatment. Statistically significant increase in the incidence and multiplicity of lung tumors was observed in rasH2 mice treated with BHT following exposure to all of the carcinogens tested. The data overall suggest the rasH2/BHT model to be a powerful screening tool for genotoxic lung carcinogens. | 10.1016/j.canlet.2005.02.024 |
pubmed_964_11531 | Balsamorhiza sagittata, a species of ethnopharmacological interest in British Columbia, is reported to have antibacterial and antifungal properties. An antibacterial compound isolated from this species was identified as 7,10-epithio-7,9-tridecadiene-3,5,11-triyne-1,2-diol based on the HMQC and HMBC experiments. | 10.1055/s-2006-957802 |
pubmed_973_17440 | BACKGROUND AND OBJECTIVES
Adequate early mycophenolic acid (MPA) exposure is an important determinant for effective rejection prophylaxis. This pharmacokinetic study investigated whether an intensified dosing regimen of enteric-coated mycophenolate sodium (EC-MPS) could achieve higher mycophenolic acid (MPA) exposure early after transplantation versus a standard dosing regimen.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
De novo kidney transplant recipients (n = 75) who were treated with basiliximab induction and cyclosporine were randomly assigned to receive EC-MPS as either standard dosing (1440 mg/d; n = 37) or intensified dosing (days 0 through 14: 2880 mg/d; days 15 through 42: 2160 mg/d; followed by 1440 mg/d; n = 38). Full 12-hour pharmacokinetic and pharmacodynamic profiles were taken at six time points during the first 3 months. Exploratory analysis of inosine monophosphate dehydrogenase (IMPDH) activity was also performed for better understanding of the pharmacokinetic-pharmacodynamic relationship between MPA exposure and IMPDH activity in the early posttransplantation period. Preliminary efficacy parameters, safety, and tolerability were assessed.
RESULTS
Exposure to MPA was significantly higher on days 3 and 10 after transplantation in the intensified versus standard EC-MPS group, with 52.9 versus 22.2% (P < 0.05) of patients reaching MPA exposure >40 mg/h per L in the first week. The intensified regimen resulted in significantly lower IMPDH activity on day 3 after transplantation, and the overall safety was comparable for both groups.
CONCLUSIONS
These pharmacokinetic and safety data support further research on the hypothesis that early adequate MPA exposure could improve clinical outcome. | 10.2215/CJN.06050809 |
pubmed_6_1282 | While the coastal pollution of persistent toxic substances (PTSs) has been widely documented, information on offshore environments remains limited. Here, we investigated the spatial distribution and sources of PTSs in the offshore sediments (n = 34) of South Korea. Sediment samples collected from the Yellow Sea (n = 18), the South Sea (n = 10), and the East Sea (n = 6), in 2017-18 were analyzed for a total of 71 PTSs. Target compounds include 31 PCBs, 15 PAHs, 9 emerging PAHs (e-PAHs), 10 styrene oligomers (SOs), and 6 alkylphenols (APs). Sedimentary PCBs showed relatively low concentrations with no significant difference across the three seas (0.16-6.9 ng g-1 normalized organic carbon, OC). Low-chlorinated PCBs (tri- and tetra Cl-CBs) were predominant (mean: 77%), primarily indicating atmospheric inputs. PAHs widely accumulated in the three seas with low to moderate level (22-250 ng g-1 OC), and dominated by high molecular weight PAHs (4-6 rings). PMF analysis revealed coast-specific PAHs sources; i.e., originated from mainly coke production (77%) in the Yellow Sea, vehicle emissions (68%) in the South Sea, and fossil fuel combustion (49%) in the East Sea. SOs showed significant contamination than other PTSs, with elevated concentrations in the Yellow Sea (mean: 350 ng g-1 OC). APs showed a similar regional distribution to SOs, but concentrations were much lower (mean: 17 ng g-1 OC). SOs and APs seemed to be introduced from rivers and estuaries on the west coast of Korea, where industrial and municipal activities are concentrated, then might be transported to offshore through tide or currents. Overall, the novel data presented for various PTSs in offshore Korean sediments warrant the necessity of a long-term monitoring effort and urgent management practice to protect marine ecosystem. | 10.1016/j.scitotenv.2021.147996 |
pubmed_795_3544 | Cancer of the prostate is the most commonly diagnosed solid malignancy and the second leading cause of cancer-related death in men living in developed countries. With an ageing population, the number of men living with early stages of prostate cancer is expected to increase. There is an increasing need to prevent the onset of cancer or delay the progression of carcinogenesis in this organ. Chemoprevention is the administration of pharmacological agents to prevent, delay or reverse carcinogenesis. An example is the reversal of high grade intraepithelial neoplasia by hormonal manipulation using anti-oestrogens in breast carcinogenesis or anti-androgens in prostate carcinogenesis. Epidemiological data showing ethnic and geographic variations in the incidence of, and mortality from, prostate cancer have suggested that the consumption of certain dietary factors, particularly anti-oxidants, may be protective. These factors include the vitamins D and E, soy, lycopene and selenium. The administration of 5-alpha reductase inhibitors to patients with benign prostatic hyperplasia may also constitute a potentially chemopreventive intervention. The efficacy of chemopreventive agents needs to be investigated in randomised, placebo-controlled trials in suitable cohorts of high-risk individuals. In parallel, reliable assays of potential biomarkers of the efficacy of intervention need to be developed and validated rigorously. | pubmed_795_3544 |
pubmed_399_5971 | Transplantation of human tumors into the organ or tissue of their origin (orthotopic transplantation) in nude mice can result in significant enhancement of tumor growth and metastases, compared with sc (ectopic) transplantation. Because melanocytes are normally found in the epidermal-dermal junction, intradermal inoculation of melanoma cells might be expected to improve their potential for malignant growth as xenografts. The purpose of our study was to examine this possibility. We found that because mouse epidermis and dermis are so thin, it was not possible to inject a bolus of tumor cells intradermally; instead the cells were actually deposited in the most superficial layer of the subcutis (i.e., subdermally). We evaluated the behavior of cells from a human melanoma cell line after sc or subdermal inoculation into National Institutes of Health Swiss athymic nude mice. The cells used were from (1) the predominantly amelanotic human malignant melanoma cell line MeWo, originally established from a melanotic lymph node metastasis, and (2) two MeWo variants resistant to wheat germ agglutinin (WGAr), which were selected for altered malignant capacities. Whereas 5 X 10(5) MeWo cells were required to achieve 100% tumor take with sc injection, only 2 x 10(4) cells were required with subdermal inoculation. Subdermal injection of the MeWo cells resulted in the development of highly melanotic and nonencapsulated primary tumors, which grew quickly into the dermis and epidermis and metastasized at high frequency to draining lymph nodes. In contrast, the tumors that developed after sc injection were found in the deepest layer of the subcutis and were predominantly amelanotic and encapsulated; they rarely metastasized to lymph nodes.(ABSTRACT TRUNCATED AT 250 WORDS) | 10.1093/jnci/81.12.938 |
pubmed_506_7217 | Changes observed in the reflection anisotropy spectroscopy (RAS) profiles of monolayers of cytochrome P450 reductase adsorbed at Au(110)-electrolyte interfaces at 0.056 V following the addition of nicotinamide adenine dinucleotide phosphate (NADP(+)) are explained in terms of a simple model as arising from changes in the orientation of an isoalloxazine ring located in the flavin mononucleotide binding domain of the protein. The model also accounts for the changes observed in the RAS as the potential applied to the Au(110) surface is varied and suggests that differences in the dependence of the RAS profile of the adsorbed protein on the potential applied to the electrode in the absence and presence of NADP(+) are explicable as arising from a competition between the applied potential acting to reduce the protein and the NADP(+) to oxidize it. | 10.1103/PhysRevE.90.022708 |
pubmed_917_9417 | Pyronin Y [3,6-bis(dimethylamino)xanthylium chloride; PY] and toluidine blue O [tolonium chloride; 3-amino-7-(dimethylamino)-2-methyl phenothiazin-5-ium chloride; TB] are cationic dyes commonly used in cytochemistry that have affinity to nucleic acids, predominantly to RNA. In live cells these dyes accumulate in mitochondria and sensitize the cells to light. The photosensitizing effects of PY and TB were compared with those of another mitochondrial cationic dye, rhodamine 123, and a noncationic dye, merocyanine 540, which binds to the cell membrane. Ninety % reduction of clonogenicity of human epidermoid carcinoma (A-253) cells pretreated with 3.3 microM PY, 0.67 microM TB, 13 microM rhodamine 123, or 18 microM merocyanine 540 was achieved by cell exposure to 0.7, 1.0, 1.2, or 1.5 J/cm2 doses of white light, respectively. The above concentrations of PY, TB, or merocyanine 540 represent the maximal ones at which the effect of each of these dyes alone, in the dark, in reducing cell clonogenicity was less than 12%. Exposure of A-253 cells to light at doses reducing clonogenicity by 50% caused a transient (24 h) arrest of the surviving cell population in the G1 phase of the cell cycle. In contrast to A-253 cells, Chinese hamster ovary cells were highly resistant to the photosensitizing effects of each of the four dyes. Also, the normal human lung fibroblasts (WI-38) were highly resistant to photosensitization by PY, whereas the simian virus 40-transformed WI-38 cells and another carcinoma line (OV-3) were sensitive. The data suggest that PY and TB, like other mitochondrial dyes, may have a selective antitumor photosensitizing activity. | pubmed_917_9417 |
pubmed_1010_942 | JCVI-syn3A is a minimal bacterial cell with a 543 kbp genome consisting of 493 genes. For this slow growing minimal cell with a 105 min doubling time, we recently established the essential metabolism including the transport of required nutrients from the environment, the gene map, and genome-wide proteomics. Of the 452 protein-coding genes, 143 are assigned to metabolism and 212 are assigned to genetic information processing. Using genome-wide proteomics and experimentally measured kinetic parameters from the literature we present here kinetic models for the genetic information processes of DNA replication, replication initiation, transcription, and translation which are solved stochastically and averaged over 1,000 replicates/cells. The model predicts the time required for replication initiation and DNA replication to be 8 and 50 min on average respectively and the number of proteins and ribosomal components to be approximately doubled in a cell cycle. The model of genetic information processing when combined with the essential metabolic and cell growth networks will provide a powerful platform for studying the fundamental principles of life. | 10.3389/fmolb.2019.00130 |
pubmed_866_17951 | Purpose
We reported previously that retinas of mice with inherited retinal degeneration make less protein than retinas of normal mice. Despite recent studies suggesting that diminished protein synthesis rates may contribute to neurologic disorders, a direct link between protein synthesis rates and the progression of neurodegeneration has not been established. Moreover, it remains unclear whether reduced protein synthesis could be involved in retinal pathogenesis. Dysregulation of AKT/mTOR signaling has been reported in the retina during retinal degeneration, but to what extent this signaling contributes to translational attenuation in these mice remains uncertain.
Methods
C57BL/6J and rd16 mice were subcutaneously injected with anisomycin to chronically inhibit protein synthesis rates. An AAV2 construct encoding constitutively active 4ebp1 was subretinally delivered in wildtype animals to lower protein synthesis rates. 4ebp1/2 were knocked out in rd16 mice.
Results
Anisomycin treatment lowered retinal translation rates, accelerated retinal degeneration in rd16 mice, and initiated cell death in the retinas of C57BL/6J mice. AAV-mediated transfer of constitutively active 4ebp1-4A into the subretinal space of wildtype animals inhibited protein synthesis, and led to reduced electroretinography amplitudes and fewer ONL nuclei. Finally, we report that restoring protein synthesis rates by knocking out 4ebp1/2 was associated with an approximately 2-fold increase in rhodopsin levels and a delay in retinal degeneration in rd16 mice.
Conclusions
Our study indicates that protein synthesis inhibition is likely not a cell defense mechanism in the retina by which deteriorating photoreceptors survive, but may be harmful to degenerating retinas, and that restoring protein synthesis may have therapeutic potential in delaying the progression of retinal degeneration. | 10.1167/iovs.19-27512 |
pubmed_146_16861 | Batch pressure vessels commonly used for hydrothermal liquefaction have typical heating times in the range of 30 to 60 min. Thermodynamically, the complex set of reactions are path dependent, so that the heating rate can possibly affect yields and the composition of the resultant liquid products. It is postulated that the mode of heat transfer becomes an uncontrolled variable in kinetic studies and can seriously impact scale-up. To confirm this hypothesis and minimize these heat-transfer-related artifacts, we designed a batch pressure vessel equipped with an induction heating system, which allows the reduction of heat-up times by about two orders of magnitude to several seconds, compared to tens of minutes with standard pressure reactors. This system was used to study the direct liquefaction of corn stover and aspen wood with a pretreatment. The heating rate was found to have no significant effect on the composition of the liquid products. However, the liquid yields are dependent on the heating rate. Varying the cooling rate does not show obvious effects. The results confirm that the heating rate, as governed by the mode of heat transfer, is an important factor that needs to be considered during scale-up. | 10.1007/s12010-008-8131-5 |
pubmed_163_1240 | Our paper about the impacts of the Laschamps Geomagnetic Excursion 42,000 years ago has provoked considerable scientific and public interest, particularly in the so-called Adams Event associated with the initial transition of the magnetic poles. Although we welcome the opportunity to discuss our new ideas, Hawks’ assertions of misrepresentation are especially disappointing given his limited examination of the material. | 10.1126/science.abh3655 |
pubmed_891_6590 | BACKGROUND
Jurisdictions participating in Strengthening the US Response to Resistant Gonorrhea (SURRG) implemented specimen collection for culture and antimicrobial susceptibility testing from a sample of persons of all genders (at multiple anatomic sites) attending sexually transmitted disease clinics and community clinics. We describe the percentage and characteristics of patients whose isolates demonstrated reduced susceptibility (RS) to azithromycin, ceftriaxone, or cefixime.
METHODS
We included patients from clinics that participated in SURRG whose isolates underwent antimicrobial susceptibility testing by Etest. We defined RS as azithromycin minimum inhibitory concentrations (MICs) ≥2 μg/mL (AZM-RS), ceftriaxone MICs ≥0.125 μg/mL (CRO-RS), or cefixime MICs ≥0.25 μg/mL (CFX-RS). Patients with repeated infections appeared >1 time in the data. We calculated the frequency and percentage of patients with an isolate demonstrating RS by epidemiological characteristics.
RESULTS
During the period 2018-2019, 10,013 patients from 8 jurisdictions provided 10,735 isolates. Among 10,013 patients, 11.0% (n = 1099) had ≥1 isolate with AZM-RS (range by jurisdiction, 2.5%-18.0%). Approximately 11.3% of 8771 of patients visiting sexually transmitted disease clinics and approximately 8.8% of 1242 patients visiting community clinics had an AZM-RS isolate. Nearly 6% of 1013 females had an AZM-RS isolate; among males, the percents of patients with an AZM-RS isolate were 17.7% among 4177 men who have sex only with men and 6.1% among 3581 men who have sex only with women. Few (0.4%) patients had isolates with CFX-RS (n = 40) or CRO-RS (n = 43).
CONCLUSIONS
Although infections with reduced cephalosporin susceptibility were rare, AZM-RS infections were prevalent in this sample of patients in multiple jurisdictions and across gender and gender of sex partner categories. | 10.1097/OLQ.0000000000001541 |
pubmed_1045_20392 | OBJECTIVE
To estimate the postmenopausal breast cancer risk associated with total fat intake, different types and relative proportions of dietary fat using a nested, matched case-control study within the Malmö Diet and Cancer (MDC) cohort, Sweden.
METHODS
Among women 50 years or older at baseline (n = 12,803), incident breast cancer cases (n = 237) were matched to controls (n = 673) on age and screening date. Data were obtained by a "novel" diet history method, a structured questionnaire, and anthropometric measurements. Conditional logistic regression examined breast cancer risks associated with quintiles of fat intake residuals adjusted for energy and potential confounders.
RESULTS
Saturated fat and the omega3-omega6 fatty acid ratio were not related to increased risks, but positive trends were seen for total (p = 0.031), monounsaturated (p = 0.002), and polyunsaturated fat (p = 0.0009), especially omega6 fatty acids and the polyunsaturated-saturated fat ratio (p = 0.004). With mutual adjustment for different types of fat, an elevated risk remained significant in the highest omega6 fatty acid quintile (RR= 2.08, 95% CI 1.08-4.01).
CONCLUSIONS
Postmenopausal breast cancer was positively associated with total, monounsaturated, and polyunsaturated fat. However, with mutual adjustment for other types of fat, specifically high intakes of omega6 fatty acids were associated with an increased risk. | 10.1023/a:1021922917489 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.