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pubmed_1000_13496 | Previous studies have demonstrated that a loss of parvalbumin-immunoreactive (PV-ir) neurones is observed in the hippocampus after transient cerebral ischaemia. However, whether the loss of parvalbumin (PV) immunoreactivity is related to the over-production of nitric oxide (NO) during cerebral ischaemia has not been evaluated. This study was designed to test the effect of 7-nitroindazole pre-treatment (7-NI, 50 mg/kg), a selective neuronal NO synthase inhibitor, on PV immunoreactivity and its cellular activity following forebrain ischaemia. PV-ir neurones in the hippocampus of the control group were widely distributed in the pyramidal cell layer and stratum oriens of CA1 and CA3, and the granular cell layer of dentate gyrus. 7-NI pre-treatment completely suppressed the reduction of PV immunoreactivity in CA1 that was observed in the ischaemia-induced group. Subsequently, 7-NI pre-treatment also protected against the structural loss of microtubule-associated protein 2 (MAP2) immunoreactivity in CA1 after ischaemic insult. In addition, the Fos-defined neuronal activity of PV-ir neurones was slightly increased by the 7-NI pre-treatment 3 h after ischaemia. Based on these data, we conclude that the neuronal toxicity of NO may be involved in the loss of PV-ir neurones after cerebral ischaemia. | 10.1046/j.1439-0264.1999.00218.x |
pubmed_976_4285 | A large proportion of right-hemisphere stroke patients show hemispatial neglect, a neurological deficit of perception, attention, representation, and/or performing actions within their left-sided space, inducing many functional debilitating effects on everyday life, and responsible for poor functional recovery and ability to benefit from treatment. This spatial cognition disorder affects the orientation of behavior with a shift of proprioceptive representations toward the lesion side. This shift is similar to that produced by psychophysical manipulations as a wedge-prism exposure in normal healthy subjects. In both subjects, one major compensative effect of short-term prism adaptation is a shift of proprioceptive representations, demonstrated by a shift in manual straight-ahead pointing in the dark, in a direction opposite to the visual shift. In neglect patients, prism adaptation involves the shift of proprioceptive representations to the left with a reduction of rightward bias observed in neglect patients in visuo-manual tasks as line-bisection, line-cancellation or copy drawing. Improvement of neglect is also observed in no visuo-manual tasks as mental imagery, auditory extinction or posture. This generalization of prism adaptation effects at different neglect level symptoms suggests that the process of prism adaptation may activate brain functions related to multisensory integration and higher spatial representations. Moreover the positive effects found for both sensorimotor and more cognitive spatial functions lasted for at least two or more hours after prism removal. Unlike reduction of neglect through sensory stimulations, the long-lasting improvement of neglect after prism adaptation suggests the activation of short-term plasticity of brain functions related to coordinate transformations and space representations. Lastly, the duration of these effects could be useful in rehabilitation programs, as suggested by the effects of prism adaptation on disabling neglect symptoms as wheelchair driving, posture or writing. | 10.1016/S0079-6123(03)42019-0 |
pubmed_601_6921 | The connections between the pericruciate cortex and the medullary reticulospinal (RS) neurons were studied in anesthetized cat. Intracellular recordings were made from reticulospinal neurons and the effects of stimulating different areas of the pericruciate cortex were compared. EPSPs were elicited in all the 93 neurons studied which were antidromically activated by spinal stimulation and had an IS-SD notch on the ascending limb of their antidromic spikes. According to the conduction velocity (c.v.) of the axon and the minimal EPSP latency to cortical stimulation, the neurons could be divided into two groups, i.e. fast-conducting RS neurons (FRS neurons, c.v. greater than 45 m/s) and slow-conducting RS neurons (SRS neurons, c.v. less than 45 m/s). The minimal latencies of FRS neurons were equal to or shorter than 2 ms whereas those of SRS neurons were longer than 2 ms. EPSPs with short latency (less than 2 ms) could be evoked in FRS neurons by stimulating a relatively wide cortical area including the major part of precruciate area 4 and area 6, with a central area of strongest excitatory effect located in area 4 slightly medial to the tip of the cruciate sulcus. Stimulation of the postcruciate area 4 only produced long latency EPSPs. By extrapolation from the cortical and peduncular latencies and the conducting distances it was revealed that the earliest part of the minimal latency EPSPs were monosynaptically evoked in FRS neurons and were mediated by fast-conducting corticobulbar fibers. FRS neurons could be excited by stimuli applied to both ipsilateral and contralateral pericruciate cortex. The influence from the contralateral cortex was slightly stronger. | 10.1007/BF00235626 |
pubmed_563_2071 | Objective
To investigate the efficacy of conventional rehabilitation alone and conventional rehabilitation combined with aerobic training on muscle strength and function, health condition, and quality of life for patients with stable idiopathic inflammatory myopathy (IIM).
Methods
This is a historical retrospective cohort study, in which the medical records of patients with IIM, who received the combination of conventional rehabilitative therapy and aerobic training (combined training group [CTG]), from February 2015 to December 2017 were reviewed. Patients with IIM who received conventional therapy alone were matched based on their age, gender, and disease activity as the control group (CG). Scores obtained on manual muscle testing of eight designated muscles (MMT8) was the primary outcome measure, and scores on the myositis Functional Index-2 (FI-2), Health Assessment Questionnaire (HAQ), and 36-item Short Form Medical Outcomes Study Questionnaire (SF-36) at 12 weeks during training were the secondary outcomes.
Results
Fifty-six patients (28 in the CTG and 28 in the CG) were included in this analysis. Patients in both groups had improved MMT8, FI-2, HAQ, and SF-36 scores after 12 weeks of physical therapy. The CTG had a significantly higher score on the MMT8 and HAQ than the CG in the 12th week. The FI-2 scores were significantly higher in the CTG for the four items (P < 0.05) of hip flexion, step test, heel lift, and toe lift. SF-36 scores of the CTG were also higher than those of the CG for the five items (P < 0.05) of physical functioning, general health, vitality, social functioning, and mental health.
Conclusions
Physical exercise training including conventional rehabilitation and aerobic training improved muscle function, health condition, and quality of life. Conventional rehabilitative training combined with aerobic training achieved better improvement compared with conventional rehabilitation training alone. | 10.2478/rir-2022-0004 |
pubmed_662_1427 | This study evaluates the noncovalent bonding of anionic antibiotics to polytetrafluoroethylene grafts using benzalkonium chloride as a cationic anchor. The binding of radiolabeled surfactants and antibiotics was evaluated by liquid scintillation and in an in vitro microbiologic assay against Staphylococcus aureus. Significant quantities of antibiotic were bound when the grafts were pretreated with benzalkonium in ethanol or aqueous solution at elevated temperature. Bound antibiotic is stable in aqueous salt solutions, but slowly dissociates in the presence of blood or serum. The ionic nature of the bonding process is clarified by the use of a variety of antibiotics and surfactants with complementary charges. The ability of the benzalkonium treated grafts to adsorb antibiotic from blood is, likewise, demonstrated and the possibility of concomitantly binding heparin and antibiotic simultaneously is evaluated. These studies support the ability to noncovalently bond antibiotics to polytetrafluoroethylene surfaces and form the basis of eventually utilizing these surfaces in the prevention of vascular prosthetic infections. | 10.1097/00000658-198111000-00015 |
pubmed_821_14915 | Two patients with similar courses of neurologic impairment and subsequent recovery after cerebral air embolism complicating cardiac ablation procedures are described. Hyperbaric oxygen therapy, combined with aggressive resuscitative efforts, appears to have contributed to each patient's recovery. | 10.1212/wnl.56.6.792 |
pubmed_1071_14878 | OBJECTIVE
The purpose of this research was to describe perceived barriers to physical activity among pregnant women living in a rural community.
DESIGN AND SAMPLE
The project followed a simple descriptive design. The sample included 88 healthy pregnant women from a rural community in the southeast United States.
MEASURES
The women completed the International Physical Activity Questionnaire (IPAQ) and an open-ended item seeking a description of personal barriers to engagement in regular physical activity.
RESULTS
Scores on the IPAQ were generally equally distributed across categories of low, moderate, and high activity. A total of 42 barriers was described from 34% of the women. Seven themes emerged among the reported barriers: (1) symptoms of pregnancy, (2) family and childrearing activities, (3) lack of personal motivation, (4) time and employment demands, (5) perceptions of sufficient activity from daily life, (6) fear of injury, and (7) lack of a habit of activity.
CONCLUSIONS
Barriers reported by the rural women were similar to those identified in other settings. Some perceptions confirmed myths about the health value of exercise during pregnancy, but did not confirm barriers commonly cited or assumed for reduced physical activity among rural residents. | 10.1111/phn.12006 |
pubmed_1084_11205 | BACKGROUND
The International Physical Activity Questionnaire-Short Form (IPAQ-SF) has been recommended as a cost-effective method to assess physical activity. Several studies validating the IPAQ-SF have been conducted with differing results, but no systematic review of these studies has been reported.
METHODS
The keywords "IPAQ", "validation", and "validity" were searched in PubMed and Scopus. Studies published in English that validated the IPAQ-SF against an objective physical activity measuring device, doubly labeled water, or an objective fitness measure were included.
RESULTS
Twenty-three validation studies were included in this review. There was a great deal of variability in the methods used across studies, but the results were largely similar. Correlations between the total physical activity level measured by the IPAQ-SF and objective standards ranged from 0.09 to 0.39; none reached the minimal acceptable standard in the literature (0.50 for objective activity measuring devices, 0.40 for fitness measures). Correlations between sections of the IPAQ-SF for vigorous activity or moderate activity level/walking and an objective standard showed even greater variability (-0.18 to 0.76), yet several reached the minimal acceptable standard. Only six studies provided comparisons between physical activity levels derived from the IPAQ-SF and those obtained from objective criterion. In most studies the IPAQ-SF overestimated physical activity level by 36 to 173 percent; one study underestimated by 28 percent.
CONCLUSIONS
The correlation between the IPAQ-SF and objective measures of activity or fitness in the large majority of studies was lower than the acceptable standard. Furthermore, the IPAQ-SF typically overestimated physical activity as measured by objective criterion by an average of 84 percent. Hence, the evidence to support the use of the IPAQ-SF as an indicator of relative or absolute physical activity is weak. | 10.1186/1479-5868-8-115 |
pubmed_854_22647 | Adeno-associated virus (AAV) vectors can be used to introduce site-specific mutations into homologous chromosomal sequences. There are many potential applications of this technique, but the process of AAV-mediated gene targeting and factors that influence targeting efficiency are not completely understood. We investigated the dependence of AAV-mediated gene targeting on the host cell-cycle status. The frequency of gene targeting by AAV vectors was compared in dividing and serum-arrested normal human fibroblast cultures. Gene targeting occurred in arrested fibroblast cultures at 0.15 to 1.1% the frequency of dividing cultures, and only took place in cells that had undergone DNA synthesis. Gene targeting was also reduced when DNA synthesis was inhibited by hydroxyurea. | 10.1089/hum.2005.16.522 |
pubmed_776_12527 | Cervical esophageal webs are a relatively common finding on esophograms. We report a web resulting from the squamocolumnar junction produced by heterotopic gastric mucosa. The clinical significance of this lesion is discussed and the importance of differentiating it from Barrett's esophagus is stressed. | 10.1007/BF00198108 |
pubmed_575_25567 | Post-partum psychosis (PPP) is a severe psychiatric emergency. The condition is rare and has generally not been an area of overwhelming research, and concordantly, early identification and treatment is a challenge. Research in the field suggests, that PPP often is a bipolar spectrum illness, and resent research has identified the most common symptoms. This review is an updated description of the phenotypical characteristics of the illness and treatment recommendations based on the newest research. | pubmed_575_25567 |
pubmed_227_12530 | Lymphopenia is defined as a peripheral lymphocyte count lower than 1500/mm3 in adults and 4500/mm3 in children younger than eight months of age. We propose a classification of lymphopenia according to the mechanism involved: lymphocyte production defects, including primary immune deficiencies and immune deficiencies secondary to malnutrition or zinc deprivation; excess catabolism, due to causes including radiotherapy, chemotherapy, immunosuppressive therapy, HIV infection, and systemic lupus erythematosus; abnormal lymphocyte trapping, including mainly splenomegaly, certain viral infections, septic shock, extended burns, systemic granulomatosis, and corticosteroids; other causes of lymphocytopenia, with mechanisms that remain poorly understood: ethnicity (Ethiopians), lymphoma, renal insufficiency, and idiopathic CD4 lymphocytopenia. | 10.1016/s0755-4982(06)74709-1 |
pubmed_715_11348 | We recently reported on the involvement of a RecA-LexA-dependent pathway in the ciprofloxacin-triggered upregulation of fibronectin-binding proteins (FnBPs) by fluoroquinolone-resistant Staphylococcus aureus. The potential additional contribution of the transcription factor sigma B (SigB) to the ciprofloxacin-triggered upregulation of FnBPs was studied in isogenic mutants of fluoroquinolone-resistant strain RA1 (a topoisomerase IV gyrase double mutant of S. aureus NCTC strain 8325), which exhibited widely different levels of SigB activity, as assessed by quantitative reverse transcription-PCR of their respective sigB and SigB-dependent asp23 transcript levels. These mutants were Tn551 insertion sigB strain TE1 and rsbU(+) complemented strain TE2, which exhibited a wild-type SigB operon. Levels of FnBP surface display and fibronectin-mediated adhesion were lower in sigB mutant TE1 or higher in the rsbU(+)-restored strain TE2 compared to their sigB(+) but rsbU parent, strain RA1, exhibiting low levels of SigB activity. Steady-state fnbA and fnbB transcripts levels were similar in strains TE1 and RA1 but increased by 4- and 12-fold, respectively, in strain TE2 compared to those in strain RA1. In contrast, fibronectin-mediated adhesion of strains TE1, RA1, and TE2 was similarly enhanced by growth in the presence of one-eighth the MIC of ciprofloxacin, which led to a significantly higher increase in their fnbB transcript levels compared to the increase in their fnbA transcript levels. Increased SigB levels led to a significant reduction in agr RNAIII; in contrast, it led to a slight increase in sarA transcript levels. In conclusion, upregulation of FnBPs by increased SigB levels and ciprofloxacin exposure in fluoroquinolone-resistant S. aureus occurs via independent pathways whose concerted actions may significantly promote bacterial adhesion and colonization. | 10.1128/AAC.49.3.916-924.2005 |
pubmed_932_4083 | Developing biomaterials to promote stem cell proliferation and differentiation is a critical requirement in tissue engineering and regeneration. Extracellular matrix (ECM) derived from mesenchymal stem cells (MSCs) has recently been shown to be able to maintain the differentiation potential of MSCs during culture expansion and to restore the activities of aging MSCs, suggesting that MSC ECM (MECM) may be a suitable culture substrate to enhance the bioactivity of biomaterial scaffolds for MSCs. This investigation aims to characterize the biological nature and specificity of the influence of the MECM on MSCs. Native ECM produced by human MSC in vitro was extracted in urea, and the residual pellet was further processed with pepsin digestion (denoted as U-MECM and HP-MECM, respectively). The MECM products were then coated as a substrate on standard tissue culture plastic, and the behavior of MSCs seeded on the coated surfaces was studied. Our results showed that U-MECM coating dramatically accelerated MSC proliferation, attachment, spread, migration and multi-lineage differentiation (i.e., osteogenesis and adipogenesis), compared to collagen type I and HP-MECM coating. Non-collagenous proteins are likely the bioactive components in U-MECM, as MSCs cultured on collagen type I and HP-MECM showed similar biological activities, and collagen type I appeared to be the major protein components remaining in HP-MECM based on SDS-PAGE. These findings support the biological utility of MECM in the formulation of biomaterial scaffolds to enhance MSC bioactivities, including proliferation, migration and multi-lineage differentiation, for tissue regeneration applications. | 10.1016/j.biomaterials.2012.03.012 |
pubmed_74_10488 | PURPOSE
To describe in detail the temporal bone and brain findings in both common and rare syndromic causes of hearing loss, with the purpose of broadening among radiologists and enhance the current understanding of distinct imaging features in paediatric patients with syndromic hearing loss.
METHODS
A detailed search of electronic databases has been conducted, including PubMed, Ovid Medline, Scopus, Cochrane Library, Google Scholar, National Institute for Health and Care Excellence (NICE), Embase, and PsycINFO.
RESULTS
Syndromic causes of hearing loss are characterised by different and sometimes specific abnormalities in the temporal bone.
CONCLUSION
A complete knowledge of the image findings in the temporal bones, brain, skull and other body regions is critical for the optimal assessment and management of these patients. | 10.1016/j.ejrad.2019.108803 |
pubmed_74_24548 | Radiation is routinely recommended after conservative surgery for breast cancer, despite long-standing Level I evidence showing no survival benefit for elderly patients with favorable disease using endocrine therapy. We sought to evaluate radiation use and costs in patients eligible for omission of radiation. A retrospective single-institution review from 2005 to 2017 was performed of women aged ≥70 years, with cT1N0M0, who were ER/PR positive and HER-2 negative, and receiving breast-conserving surgery. Patient, tumor, and treatment characteristics were compared by use of radiation. Cost estimates used Medicare's 2019 fee schedule. Of 84 patients meeting the study criteria, 72.6 per cent received radiation and 56 per cent received endocrine therapy, with four recurrences (4.9% radiated and 4.4% not radiated, P = 0.9). Early and late grade I radiation toxicities occurred in 67.2 per cent and 26.2 per cent of radiated patients, respectively. Younger age (P = 0.01), receipt of endocrine therapy (P < 0.0001), and axillary surgery (P < 0.0001) were significantly associated with radiation use. There were no significant differences in radiation use based on race/ethnicity, language, comorbidities, BMI, or pathologic tumor size. Estimated total radiation cost was $646,426. Radiation remains overused and endocrine therapy, underused in breast cancer patients eligible to avoid radiation. As gatekeepers for radiation oncology referrals, surgeons can diminish both physical and financial costs of radiation in eligible patients. | pubmed_74_24548 |
pubmed_910_3413 | OBJECTIVES
Vocal fry is a voice register often used by young adult women for sociolinguistic purposes. Some acoustic correlates of lexical stress, however, appear incompatible with the use of vocal fry. The objective of this study was to systematically examine the role of lexical stress in the use of vocal fry by young adult women.
STUDY DESIGN
This is a semi-randomized controlled laboratory study.
METHODS
Fifty female undergraduate students were recorded repeating one-, two-, three-, and four-syllable nonwords that conformed to English phonotactics. Nonwords were presented in order from shorter to longer lengths, with stimuli randomized within syllable length. Perceptual analyses of recordings were augmented by acoustic analyses to identify each syllable in which vocal fry occurred.
RESULTS
Eighty-six percent of participants produced at least one episode of vocal fry. Vocal fry was more likely to occur in unstressed than stressed position, and the likelihood increased as distance from the stressed syllable increased. There was considerable variability in the use of vocal fry. Frequent and infrequent users varied on the degree to which they used vocal fry in single-syllable nonwords.
CONCLUSIONS
Vocal fry use persists among young adult women even in the absence of syntactic and pragmatic influences. Lexical stress appeared to dramatically reduce the use of vocal fry. Patterns of vocal fry use appeared to be different for frequent and infrequent users of this vocal register. | 10.1016/j.jvoice.2016.02.005 |
pubmed_1123_8569 | A Compton suppressed high-purity germanium (HPGe) detector is well suited to the analysis of low levels of radioactivity in environmental samples. The difference in geometry, density and composition of environmental calibration standards (e.g. soil) can contribute to excessive experimental uncertainty to the measured efficiency curve. Furthermore multiple detectors, like those used in a Compton suppressed system, can add complexities to the calibration process. Monte Carlo simulations can be a powerful complement in calibrating these types of detector systems, provided enough physical information on the system is known. A full detector model using the Geant4 simulation toolkit is presented and the system is modelled in both the suppressed and unsuppressed mode of operation. The full energy peak efficiencies of radionuclides from a standard source sample is calculated and compared to experimental measurements. The experimental results agree relatively well with the simulated values (within ∼5 - 20%). The simulations show that coincidence losses in the Compton suppression system can cause radionuclide specific effects on the detector efficiency, especially in the Compton suppressed mode of the detector. Additionally since low energy photons are more sensitive to small inaccuracies in the computational detector model than high energy photons, large discrepancies may occur at energies lower than ∼100 keV. | 10.1016/j.jenvrad.2011.10.017 |
pubmed_2_17414 | BACKGROUND AND PURPOSE
Target volume definitions for radiotherapy in pancreatic ductal adenocarcinoma (PDAC) vary substantially. Some groups aim to treat the primary tumor only, whereas others include elective lymph nodes (eLNs). eLNs close to the primary tumor are often included unintentionally within the treatment volume, depending on the respective treatment philosophies. We aimed to measure the percentages of anatomical coverage of eLNs by comparing four different contouring guidelines.
PATIENTS AND METHODS
Planning target volumes (PTVs) were contoured using planning computed tomography (CT) scans of 11 patients with PDAC based on the Oxford, RTOG (Radiation Therapy Oncology Group), Michigan, and SCALOP (Selective Chemoradiation in Advanced Localised Pancreatic Cancer trial) guidelines. Clinical target volumes (CTVs) included the peripancreatic, para-aortic, paracaval, celiac trunk, superior mesenteric, and portal vein lymph node areas. Volumetric comparisons of the coverage of all eLN regions were conducted to illustrate the differences between the four contouring strategies.
RESULTS
The PTV sizes of the RTOG and Oxford guidelines were comparable. The SCALOP and Michigan PTV sizes were similar to each other and significantly smaller than the RTOG and Oxford PTVs. A large variability of eLN coverage was found for the various subregions according to the respective contouring strategies.
CONCLUSION
This is the first study to directly compare the percentage of anatomical coverage of eLNs according to four PTVs in the same patient cohort. Potential practical consequences are discussed in detail. | 10.1007/s00066-013-0332-3 |
pubmed_772_1640 | From hit compounds identified by high throughput screening (HTS), we have found compound 1 as a lead TRPV1 antagonist and confirmed its potential as a treatment for pain. Compound 1 has led to potent TRPV1 antagonistic benzamide derivatives ((+/-)-2: human IC(50)=23 nM, (+/-)-3: human IC(50)=14 nM in the capsaicin-induced calcium influx assay) containing indole and naphthyl moieties, obtained by elaboration of the tryptamine scaffold or via bioisosteric replacements. | 10.1016/j.bmcl.2007.12.007 |
pubmed_994_5560 | INTRODUCTION
The performance of factor XI activity (FXI) by laboratories in the North American Specialized Coagulation Laboratory Association proficiency testing program was analyzed.
METHODS
Over 10 years (2003-2013), 80 samples were distributed; 33-55 laboratories participated per exercise providing 3833 total responses. Analysis was performed on numeric results and qualitative classification of results.
RESULTS
The sample FXI levels ranged from 3.8 to 154.0 IU/dL. The overall interlaboratory average coefficient of variation (CV%) was 17.5%; the CV was higher for a sample with low (3.8 IU/dL) FXI. Results were correctly classified as abnormal (100%) for a sample with 3.8 IU/dL FXI and normal/borderline normal (97.7%) for 45 samples with 80 to < 140 IU/dL FXI. The classification was heterogeneous for samples with FXI of 50 to < 80 IU/dL. Six specimens were repeat-tested from 2007 to 2013. The mean FXI was not significantly different in laboratories using the same method on both exercises, suggesting good intralaboratory precision over time. Univariate analysis of data from 2011 to 2012 did not find a consistent significant difference among the activators, analyzers, calibrators, and FXI-deficient plasmas.
CONCLUSION
Laboratories generally performed well in assessment of FXI based on interlaboratory precision when FXI >30 IU/dL and on classification of samples with very low or normal FXI. | 10.1111/ijlh.12359 |
pubmed_704_10150 | This case series aimed to preliminarily evaluate the efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) in patients with lung, renal, gastric, and other non-liver cancers.Twenty-four patients who underwent DEB-TACE or DEB-TACE combined with other therapies were reviewed in this case series. Treatment responses were assessed at 1 month after treatment according to the modified Response Evaluation Criteria in Solid Tumors. Overall survival (OS) and adverse events were recorded.In the total patients, the objective response and disease control rate were 79.2% and 87.5%, respectively. And the mean OS in total patients was 14.7 months (95% confidence interval: 9.6-19.9 months). The number of patients who had generalized aches, nausea, vomit, fever, abdominal discomfort, chest discomfort, elevated blood pressure, cough, loss of appetite, and headache in total patients were 7 (29.2%), 11 (45.8%), 6 (25.0%), 2 (8.3%), 3 (12.5%), 3 (12.5%), 1 (4.2%), 1 (4.2%), 1 (4.2%), and 1 (4.2%), respectively. The objective response rates in patients with lung, renal, gastric, and other non-liver cancer were 70.0%, 85.7%, 100.0%, and 80.0%, respectively. In patients with lung, renal, gastric, and other non-liver cancers, the mean values of the OSs were 13.4 months, 12.4 months, 7.6 months, and 20.3 months, respectively. And the most common adverse events in lung cancer patients, renal carcinoma patients, gastric cancer patients, and patients with other non-liver cancers were post-embolization syndrome.DEB-TACE may be an effective and safe therapeutic option in patients with lung, renal, gastric, and other non-liver cancers. | 10.1097/MD.0000000000020878 |
pubmed_964_19682 | Pruritus is a significant symptom among patients receiving hemodialysis. However, its underlying mechanisms remain obscure. Substance P, a neuropeptide, has been implicated in the mediation of pain and some itch sensations. Local application of capsaicin depletes the peripheral neurons of substance P and may block the conduction of pain or pruritus. This study aims to assess the efficacy and safety of capsaicin 0.025% cream in the treatment of hemodialysis-related pruritus and to further explore the underlying pathomechanism. Nineteen hemodialysis patients with idiopathic, moderate (n = 5) to severe (n = 14) pruritus were examined in a double-blind, placebo-controlled, crossover study and 17 of them completed the study. Topical agent of capsaicin or placebo base cream was applied to localized areas of pruritus 4 times a day. The severity of pruritus and treatment-related side effects (cutaneous burning/stinging sensations, dryness, or erythema) were evaluated weekly. The results showed (1) that 14 of 17 patients reported marked relief and 5 of these 14 patients had complete remission of pruritus during capsaicin treatment (Wilcoxon signed-ranks test, 2p < 0.001); (2) capsaicin was significantly more effective than placebo (Mann-Whitney rank sum test, 2p < 0.001) and a prolonged antipruritic effect was observed 8 weeks posttreatment; (3) no serious side effects were noted during the study and (4) there were no significant changes in serum concentrations of albumin, calcium, phosphorus, alkaline phosphatase, or intact parathyroid hormone during the treatment with either capsaicin or placebo. In summary, the present study indicates indirectly that idiopathic pruritus in some patients on maintenance hemodialysis may be transmitted by substance P from the peripheral sensory neurons to the central nervous system. Topical capsaicin with the unique pharmacological effect is demonstrated to markedly improve the pruritus of these patients. | 10.1159/000188949 |
pubmed_639_15362 | BACKGROUND
Ulcerative colitis (UC) is a kind of chronic non-specific ulcerative colitis, which is characterized by repeated abdominal pain, diarrhea, and mucus purulent stool. The disease is more recurrent, easy to delay, and canceration, seriously affect the quality of life, increase the economic burden of patients and society, treatment is more difficult, the World Health Organization as one of the modern refractory diseases. Shenling Atractylodes Powder in the treatment of ulcerative colitis showed a strong advantage, the effect is accurate. Therefore, this paper will systematically evaluate and meta-analyze the efficacy and safety of heat-sensitive moxibustion in the treatment of ulcerative colitis.
METHODS
Eight electronic databases were searched, including the PubMed, Embase, Web of Science, Cochrane Library, China National knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and China Biomedical Literature Database. We will search in the above electronic database from early 2021 to December without any language restrictions. Outcome indicators, including colonic mucosal symptom score Mayo colonoscopy grading, total effective rate, total incidence of adverse reactions, clinical symptom score, recurrence rate, laboratory indicators: IL-6, IL-9, TNF-α, IL-4, IL-10 inflammation-related factor levels. Rev Man5.3 software will be used for statistical analysis. The efficacy and safety results of Shenling Atractylodes Powder in the treatment of ulcerative colitis will be used as the average difference between the risk ratio of dichotomy data and the 95% co-card interval of continuous data.
RESULTS
When this research program is completed, the relevant results can be obtained.
ETHICS AND DISSEMINATION
This article does not need to pass the ethics committee review, because this article does not involve the ethics question, only collates the related literature research. The results of this study will be disseminated in the form of a paper to help better guide the clinical practice of heat-sensitive moxibustion in the treatment of ulcerative colitis.
REGISTRATION NUMBER
INPLASY202120018. | 10.1097/MD.0000000000025355 |
pubmed_634_978 | This work investigated the effectiveness of zerovalent iron and Fe/Ni bimetallic nanoparticles in the treatment of water polluted by a high concentration of nitrates. Nanoparticle synthesis was carried out by a sodium borohydride reduction method in the presence of sodium oleate as a surfactant. The particles were characterized by XRD and SEM. Batch experiments were conducted on water samples contaminated by 300 mg L-1 of nitrate. The parameters investigated were the Fe/Ni dosage (0.05, 0.1, 0.2, 0.3, and 0.4 g L-1) and the reaction pH (unbuffered; buffered at pH = 3; initial pH = 3, 5, and 10). The results showed that almost complete nitrate removal (>99.8%) was always achieved after 15 min at a concentration of bimetallic nanoparticles higher than 0.2 g L-1. The optimization of bimetallic nanoparticle dosage was carried out at a fixed pH. Kinetic study tests were then performed at different temperatures to assess the effect of temperature on the nitrate removal rate. By fixing the pH at acidic values and with an operating temperature of 303 K, nitrates were completely removed after 1 min of treatment. | 10.3390/nano9081130 |
pubmed_550_19326 | Azorhizobium caulinodans is a symbiotic diazotroph that contains duplicated nifH genes. This study focused on the biological sense behind the duplication. In-frame deletion mutants of nifH1 and nifH2 were constructed in order to analyze nitrogen fixation activity, both in symbiosis and in free-living conditions. Symbiotic nitrogen fixation activity was not affected by deletion of nifH1 or nifH2, while free-living nitrogen fixation activity was significantly decreased. Deletion of nifH1 had a significant effect in semi-aerobic condition, while deletion of nifH2 was significant in microaerobic condition, suggesting functional differences between nifH1 and nifH2. Transcriptional activity of nifH1 was higher than nifH2, both in microaerobic and semi-aerobic conditions. | 10.1111/j.1574-6968.2007.00823.x |
pubmed_317_16544 | The rise of pharmaceutical costs is a significant burden to overall health care expenditure. The Croatian Health Insurance Fund (CHIF) in attempts of its containment, use administrative measures directed toward the two greatest generators: pharmaceutical industry, through negotiating prices and periodic revisions of basic and suplemental drug lists, and primary care physicians, through limits in the volume of prescriptions, and annual financial expenditure. The aim of the study was to determine trends in quantity of issued prescriptions and pharmaceutical expanditure from 2000 to 2012. Data were obtained from the CHIF annual reports. Results clearly demonstrate two trends: the increase in quantity of issued prescriptions, together with accompanying rates: number of prescriptions per inhabitants, and per patients, and the increase in total cost of prescriptions until 2004, with their maintenance and slight variations since then. Despite controversies in approach, CHIF succeded in slowing down the costs, primarily by applying measures towards regulation of drug prices. | pubmed_317_16544 |
pubmed_541_23123 | Regulators of G-protein signaling (RGS) proteins are GTPase-activating proteins (GAPs) that bind to Galpha subunits and attenuate G protein signaling, but where these events occur in the cell is not yet established. Here we investigated, by immunofluorescence labeling and deconvolution analysis, the site at which endogenous Galpha-interacting protein (GAIP) (RGS19) binds to Galphai3-YFP and its fate after activation of delta-opioid receptor (DOR). In the absence of agonist, GAIP is spatially segregated from Galphai3 and DOR in clathrin-coated domains (CCPs) of the cell membrane (PM), whereas Galphai3-YPF and DOR are located in non-clathrin-coated microdomains of the PM. Upon addition of agonist, Galphai3 partially colocalizes with GAIP in CCPs at the PM. When endocytosis is blocked by expression of a dynamin mutant [dyn(K44A)], there is a striking overlap in the distribution of DOR and Galphai3-YFP with GAIP in CCPs. Moreover, Galphai3-YFP and GAIP form a coprecipitable complex. Our results support a model whereby, after agonist addition, DOR and Galphai3 move together into CCPs where Galphai3 and GAIP meet and turn off G protein signaling. Subsequently, Galphai3 returns to non-clathrin-coated microdomains of the PM, GAIP remains stably associated with CCPs, and DOR is internalized via clathrin-coated vesicles. This constitutes a novel mechanism for regulation of Galpha signaling through spatial segregation of a GAP in clathrin-coated pits. | 10.1124/mol.64.1.11 |
pubmed_1070_14663 | INTRODUCTION
Despite a narrow therapeutic index, lithium remains a cornerstone for the treatment of bipolar disease. As lithium poisoning may result in life-threatening neurotoxicity, measurement of the lithium concentration is mandatory in drug monitoring as well as for the diagnosis and prognostic evaluation of lithium poisoning. However, toxic symptoms do not always correlate with plasma concentrations. Therefore, more reliable indicators have been proposed, including measurement of the red blood cell (RBC) lithium concentration and the RBC-to-plasma lithium ratio.
PLASMA AND RBC LITHIUM CONCENTRATIONS
Few studies have reviewed the relative utility of these measurements both in monitoring therapy and in poisoning, and they have involved only small numbers of subjects. Moreover, factors influencing plasma and RBC lithium concentrations are numerous, including gender, age, dosage, treatment duration, co-medications, and underlying diseases. In treated patients, investigated using in vivo magnetic resonance spectroscopy, there is a significant correlation between plasma and brain lithium concentrations in steady-state conditions. In contrast, lithium transport across erythrocytes markedly differs from its transport into the central nervous system, questioning the relevance of measuring the RBC lithium concentration. In poisoned patients, plasma and RBC lithium concentrations follow a parallel decline irrespective of the type of poisoning.
CONCLUSIONS
Based on present evidence, measurement of the RBC lithium concentration and the calculation of the RBC-to-plasma lithium ratio offer no important clinical advantage over the measurement of the plasma lithium concentration, which remains the most important variable to monitor in lithium-treated or lithium-poisoned patients. | 10.1080/15563650802392398 |
pubmed_1141_4921 | During our work on the mechanism of hormone resistance of prostatic carcinomas, a novel gene that we called PAR (prostate androgen regulated) was isolated from an androgen resistant subline (LNCaP-OM) using a modified representational difference analysis. The complete sequence of the gene cDNA has 1029 nucleotides with a continuous reading frame of 438 bases encoding for 146 amino acids. Its deduced amino acid sequence has motifs for myristoylation and phosphorylation by protein kinase C. The PAR gene was overexpressed in all prostatic carcinoma cell lines studied (LNCaP, DU145, PC3 and LNCaP-OM) compared to the normal prostatic tissue. Furthermore, its expression was higher in androgen resistant prostate cancer lines DU145, PC3 and LNCaP-OM, in comparison to androgen sensitive LNCaP cells. The expression of this gene was down regulated by androgens in androgen sensitive prostate cells, but not in the hormone resistant cell lines. The PAR mRNA was detected in all 29 normal human tissues studied and overexpressed in most (67%) of their malignant counterparts. The PAR expression was higher in MCF7 and T47D breast cancer cell lines, as well as in all primary breast tumors studied compared to their normal tissue counterparts. The biological function of this gene is still unknown, but its ubiquitous expression in normal tissues and its overexpression in some malignancies suggest the PAR involvement in certain basic cellular processes and possibly, in malignant transformation. | 10.3892/ijo.16.5.1055 |
pubmed_830_9971 | BACKGROUND
Obstetrical interventions, including caesarean sections, are increasing in Canada. Canadian women's psychological states, fatigue, and sleep have not been examined prospectively for contributions to obstetric interventions and adverse neonatal outcomes.Context and purpose of the study: The prospective study was conducted in British Columbia (BC), Canada with 650 low-risk pregnant women. Of those women, 624 were included in this study. Women were recruited through providers' offices, media, posters, and pregnancy fairs. We examined associations between pregnant women's fatigue, sleep deprivation, and psychological states (anxiety and childbirth fear) and women's exposure to obstetrical interventions and adverse neonatal outcomes (preterm, admission to NICU, low APGARS, and low birth weight).
METHODS
Data from our cross-sectional survey were linked, using women's personal health numbers, to birth outcomes from the Perinatal Services BC database. After stratifying for parity, we used Pearson's Chi-square to examine associations between psychological states, fatigue, sleep deprivation and maternal characteristics. We used hierarchical logistic regression modeling to test 9 hypotheses comparing women with high and low childbirth fear and anxiety on likelihood of having epidural anaesthetic, a caesarean section (stratified for parity), assisted vaginal delivery, and adverse neonatal outcomes and women with and without sleep deprivation and high levels of fatigue on likelihood of giving birth by caesarean section, while controlling for maternal, obstetrical (e.g., infant macrosomia), and psychological variables.
RESULTS
Significantly higher proportions of multiparas, reporting difficult and upsetting labours and births, expectations of childbirth interventions, and health stressors, reported high levels of childbirth fear. Women who reported antenatal relationship, housing, financial, and health stressors and multiparas reporting low family incomes were significantly more likely to report high anxiety levels. The hypothesis that high childbirth fear significantly increased the risk of using epidural anaesthesia was supported.
CONCLUSIONS
Controlling for some psychological states and sleep quality while examining other contributors to outcomes decreases the likelihood of linking childbirth fear anxiety, sleep deprivation, and fatigue to increased odds of caesarean section. Ameliorating women's childbirth fear to reduce their exposure to epidural anaesthesia can occur through developing effective interventions. These include helping multiparous women process previous experiences of difficult and upsetting labour and birth. | 10.1186/1471-2393-12-78 |
pubmed_251_841 | We investigated the impact of attention during encoding on later retrieval. During study, participants read some words aloud (ignoring the print color) and named the print color of other words aloud (ignoring the word). Then one of two memory tests was administered. The explicit test--recognition--required conscious recollection of whether a word was studied. Previously read words were recognized more accurately than were previously color named words. This contrasted sharply with performance on the implicit test--repetition priming in lexical decision. Here, words that were color named during study showed priming equivalent to words that were read during study; both were responded to faster than unstudied words. Thus, an attentional manipulation during study had a strong effect on an explicit test of memory, but almost no effect on an implicit test. Focal attention during study is crucial for remembering consciously but not necessarily for remembering without awareness. | 10.1006/ccog.1996.0010 |
pubmed_990_10662 | The paper presents the history of technique and concepts of urinary diversion to colon and rectum from the mid-XIXth century until today, including the contribution of Polish surgeons--Kryński, Laskownicki and Kiełkiewicz. Contraindications and complications of this type of definitive urinary diversion is briefly discussed. Authors also present the outcome of ureterosigmoidostomy performed according to method proposed by Goodwin in 25 patients cystectomized for infiltrating transitional cell carcinoma of the bladder, who were operated on at the Department of Urology, Medical School in Warsaw. These patients were in poor general condition and short life expectancy, which depended upon tumour stage and grade as well as preoperative urographic evaluation of urinary tract. | pubmed_990_10662 |
pubmed_1061_4963 | Hydatidosis or echinococcosis is considered to be one of the most common zoonotic diseases of the animals. Infection occurs when intermediate hosts such as camel, cattle, sheep, and goats ingested food or water contaminated with eggs from the definitive host (dog). This is a cross-sectional study which was carried out in one of the biggest abattoirs in Makkah in the west of Saudi Arabia. A total number of 38302 goats were examined and recorded
at Makkah abattoirs. The examination had been performed to all slaughtered animals on two organs (spleen and heart) for detection of any hydatid cysts during the period from July 2018 until December 2018. The study included also histopathological tissue evaluation. The total infections number of hydatidosis in goats is 0.23%. The infected hearts were 40.35% whereas the infected spleen was 48.48% subsequently in local animals. The imported animals were 2124, the infected animals in heart were 59.64%, whereas the infected animal involving spleen were 51.51%. Meanwhile, results of histopathological examination had shown that most of the hydatid cysts in goats caused progressive focal pressure and degenerative changes in the surrounding tissue. | 10.17420/ap6503.204 |
pubmed_1095_12837 | Eight normal subjects were tested on auditory and visual choice reaction time and Tapping-Speed Test before and after two hours by administration of lorazepam (2.5 mg per os). CRTs slightly increase but not significantly; Tapping-Speed Test does not show changes. Nevertheless a significant increase of errors in all trials suggest a moderate decrease of performance after lorazepam. | pubmed_1095_12837 |
pubmed_357_20167 | The COVID-19 pandemic led to panic buying in many countries across the globe, preventing vulnerable groups from accessing important necessities. Some reports inaccurately referred to the panic buying as hoarding. Although hoarding is a separate issue characterised by extreme saving behaviour, the two problems may be influenced by similar factors. Participants from Australia and the United States (final N = 359) completed online self-report measures of panic buying, hoarding, shopping patterns, perceived scarcity, COVID-19 illness anxiety, selfishness, and intolerance of uncertainty. Our findings showed that panic buying was related to hoarding symptoms (r's = .23 - .36), and yet, both were uniquely associated with different psychological factors. Whilst panic buying was most strongly related to greater perceived scarcity (r's = .38 - .60), hoarding was most related to a general intolerance of uncertainty (r's = .24 - .57). Based on our findings, future strategies to prevent panic buying should focus on reducing perceived scarcity cues in the community, as this seems to be the primary driver of panic buying. Another preventative strategy to reduce excessive acquiring and saving may be to implement educational programs to increase people's ability to tolerate distress and uncertainty. | 10.1016/j.psychres.2021.114062 |
pubmed_841_19215 | Examined the relations between the Social Phobia and Anxiety Inventory for Children (SPAI-C) and the Social Anxiety Scale for Children-Revised (SASC-R) in community (n = 178) and clinic (n = 57) samples. A large proportion of children exceeded the recommended SPAI-C and SASC-R cutoffs for suggesting clinically significant levels of social phobia and social anxiety in the community (37% SPAI-C and 20% SASC-R) and clinic (58% SPAI-C and 42% SASC-R) samples. A large proportion of children scoring in the clinical range on the Child Behavior Checklist (CBCL) exceeded the SASC-R and SPAI-C cutoff scores; however, there was notable variability with respect to sample, age group (< or = 10 years and > or = 11 years), sex, and measure (SPAI-C vs. SASC-R, and CBCL Internalizing vs. Social Competence scale). Using the recommended cutoffs, discriminant function analyses found the classification correspondence between the SPAI-C and SASC-R was significant, with some variability found in the 2 samples, age groups, and sexes (ranging from 82% to 91% classification correspondence). These initial findings highlight a need to consider sample, age, and sex in further examination of the utility and validity of these measures and their recommended cutoffs. Implications for future work examining the linkages between social anxiety and social phobia, as well as for the assessment of children's social anxiety and social fears, are discussed. | 10.1207/S15374424JCCP3101_09 |
pubmed_410_13420 | In 2004, the identification of female germline or oogonial stem cells (OSCs) that can support post-natal oogenesis in ovaries of adult mice sparked a major paradigm shift in reproductive biology. Although these findings have been independently verified, and further extended to include identification of OSCs in adult ovaries of many species ranging from pigs and cows to non-human primates and humans, a recent study rooted in single-cell RNA sequence analysis (scRNA-seq) of adult human ovarian cortical tissue claimed that OSCs do not exist, and that other groups working with OSCs following isolation by magnetic-assisted or fluorescence-activated cell sorting have mistaken perivascular cells (PVCs) for germ cells. Here we report that rare germ lineage cells with a gene expression profile matched to OSCs but distinct from that of other cells, including oocytes and PVCs, can be identified in adult human ovarian cortical tissue by scRNA-seq after optimization of analytical workflow parameters. Deeper cell-by-cell expression profiling also uncovered evidence of germ cells undergoing meiosis-I in adult human ovaries. Lastly, we show that, if not properly controlled for, PVCs can be inadvertently isolated during flow cytometry protocols designed to sort OSCs because of inherently high cellular autofluorescence. However, human PVCs and human germ cells segregate into distinct clusters following scRNA-seq due to non-overlapping gene expression profiles, which would preclude the mistaken identification and use of PVCs as OSCs during functional characterization studies. | 10.1093/stmcls/sxac015 |
pubmed_491_12560 | ATP binding cassette (ABC) transporters can transfer a variety of antiviral agents from the cytoplasm to body fluid, which results in a reduced intracellular concentration of the drugs. Proteins of HIV-1, e.g., Tat and gp120, altered some types of ABC transporter expression in brain microvascular endothelial cells and astrocytes. However, the effect of Tat on ABC transporters in T lymphocytes is unclear. In this study the status of breast cancer resistance protein (BCRP) in Tat expressing cell lines was examined with real-time PCR and flow cytometry. It was found that HIV-1 Tat protein upregulated BCRP expression and enhanced efflux mediated by BCRP significantly, which could inhibit antiviral drugs from entering infected cells and interfere with the therapeutic effect of HAART. | 10.1089/aid.2015.0117 |
pubmed_456_20757 | BACKGROUND
The BoneBridge could rehabilitate hearing for patients with single-sided deafness (SSD).
OBJECTIVES
To evaluate the objective and subjective benefits of BoneBridge implantation in patients after vestibular Schwannoma resection and to explore the factors affecting the benefits.
MATERIAL AND METHODS
We prospectively enrolled all 15 patients implanted with BoneBridge after VS resection from January to June 2017. The primary outcome was the ability to hear in noisy conditions. The secondary outcomes were the soft-band BoneBridge try-on rate, the frequency of BB use, the sound source localization test result, and questionnaire measures of quality of life (QoL).
RESULTS
Patients showed better speech recognition ability in the presence of noise with the BoneBridge. The BoneBridge provided no help in sound localization, although most patients reported subjective sound localization benefits. The results of QoL questionnaires showed significant satisfaction with BoneBridge implantation. The unilateral hearing deprivation duration and high education levels had significant impacts on the subjective benefits of patients.
CONCLUSIONS
The BoneBridge could improve speech recognition performance in complex auditory backgrounds, as well as QoL, especially in patients with short unilateral hearing deprivation durations and high education levels.
SIGNIFICANCE
The BoneBridge is an effective hearing aid for single-sided deafness patients after VS removal. | 10.1080/00016489.2018.1469789 |
pubmed_1052_22910 | OBJECTIVE
This study investigated the reliability of the Nepali version of the 21-item Depression Anxiety Stress Scale (DASS-21) among non-clinical sample. The purpose of this paper is to report the dimensionality and internal consistency of the DASS-21in a sample of non-clinical adults.
METHOD
This study was conducted in Hong Kong among 212 Nepali adults, aged 18-60 years. Life satisfaction was assessed with the Life Satisfaction Scale. The dimensionality of the DASS-21 scale was investigated using exploratory factor analysis. Construct validity was evaluated using the life satisfaction scale.
RESULTS
The intercorrelation among depression, anxiety and stress subscales indicates that symptoms of psychological distress as measured by the DASS-21-N can distinguished between the three constructs in adult community sample. The results also showed inverse correlation among DASS-21-N and life satisfaction scale, supporting the assumption that the higher the life satisfaction, the lower the psychological distress.
CONCLUSION
The results of this study indicate that the Nepali version of the DASS-21 demonstrate adequate psychometric properties in relation to internal consistency and validity, lending support to prior studies and suggest that the DASS-21 can be utilized among diverse groups with confidence. It supports the reliability of the 3-factorial dimensionality of the DASS-21, and highlight that it is a valid and useful tool that can distinguish between depression and anxiety. | pubmed_1052_22910 |
pubmed_543_5804 | Suramin cytotoxicity was studied in a panel of human lung cancer cell lines by the MTT assay. The concentrations of suramin which induced 50% growth inhibition (IC50) ranged from 130 to 3715 microM for the cell lines growing in medium containing 10% fetal calf serum (FCS). In only one cell line was the IC50 at a concentration that can be reached in plasma of patients treated with suramin. Suramin was 18 and 3.3 times more cytotoxic on NCI-N417 cells growing in 2% FCS and in HITES serum-free medium, respectively, than growing in 10% FCS. No difference in suramin cytotoxicity was observed between small and non-small cell lung cancer cell lines. At the lower concentrations tested, suramin stimulated proliferation of the two small cell lung cancer cell lines, NCI-H187 and NCI-N417. Of several growth factors tested, none induced stimulation of growth in NCI-H187 and NCI-N417 cell lines, nor did they in any way alter the stimulatory effect of suramin. Cell counting, DNA flow cytometric analysis and Ki-67 staining confirmed a higher proliferative state in suramin-exposed NCI-H187 cells as compared with untreated cells. However, topoisomerase II-alpha gene expression remained unchanged, as assessed by northern blot analysis and immunostaining. Suramin had an inhibitory effect on topoisomerase II activity, as assessed by the kDNA decatenation assay, with an IC50 of approximately 40 microM. In conclusion, suramin has significant cytotoxic activity in a minority of human lung cancer cell lines, and it stimulates proliferation in some instances. The pleiotropic action of suramin observed should caution on the possibility of tumour acceleration in patients being treated with this drug. | 10.1016/0959-8049(94)00444-a |
pubmed_36_19966 | Raman microspectroscopy has been investigated for some time for use in label-free cell sorting devices. These approaches require coupling of the Raman spectrometer to complex data mining algorithms for identification of cellular subtypes such as the leukocyte subpopulations of lymphocytes and monocytes. In this study, three distinct multivariate classification approaches, (PCA-LDA, SVMs and Random Forests) are developed and tested on their ability to classify the cellular subtype in extracted peripheral blood mononuclear cells (T-cell lymphocytes from myeloid cells), and are evaluated in terms of their respective classification performance. A strategy for optimisation of each of the classification algorithm is presented with emphasis on reduction of model complexity in each of the algorithms. The relative classification performance and performance characteristics are highlighted, overall suggesting the radial basis function SVM as a robust option for classification of leukocytes with Raman microspectroscopy. | 10.1039/c4an01887g |
pubmed_427_6506 | Endoscopic examination of the entire colon (colonoscopy) is an important new method of diagnosis and treatment of diseases of the colon and rectum, particularly cancer. The records of 500 patients who had one or more contrast enemas and subsequent colonoscopy were analyzed in an attempt to evaluate the competitive and complementary features of the two methods. The endoscopists had the advantage of having a radiologic report or radiographs available to them. In general, when the level of abnormality could be reached, colonoscopy had a higher degree of accuracy, particularly since observation could be combined with biopsy. This was particularly true in the case of polyps in which colonoscopy confirmed 166 radiologically described growths plus an additional 118 lesion, twenty-one of which were over 1 cm in diameter. By endoscopic excision of these polyps via the colonoscope, malignant changes can be identified, a conclusion rarely reached by radiographic means alone. With respect to cancer, exclusive of polyps, only twenty-four of thirty-two cases were diagnosed by x-ray study alone. Another nine, interpreted aa demonstrating malignancy from the radiographs, had cancer excluded when subjected to endoscopic confirmation. Colonoscopy has also proved valuable in identifying lesions of the cecum, notoriously a problem for the radiologist, and in identifying milder degrees of inflammatory change which are undetectable by radiographic means. Colonoscopy and the contrast enema are best reported as completmentary rather than competitive approaches, and by their combined use, diagnostic accuracy is greatly enhanced. | 10.1016/0002-9610(75)90295-0 |
pubmed_348_15972 | Recent findings indicate a principal role for Hepcidin in iron homeostasis. Hepcidin is also thought to play a vital role in the pathogenic mechanism of anaemia in patients with inflammation or chronic disease. Under normal conditions influx and efflux of iron from duodenal enterocytes is regulated by Ferroportin. Ferroportin is a Hepcidin binding protein expressed in duodenal enterocytes. Hepcidin is a peptide synthesised in the liver and is the main regulator of iron homeostasis. It is a defensin like protein and exhibits anti-microbial and anti-fungal activity. The Hepcidin gene is principally expressed in hepatocytes but to a lesser extent in neutrophils and macrophages. Hereditary Haemochromatosis is caused by disruption of iron homeostasis due to mutations in the HFE gene (C282Y or H63D). Unrestricted uptake of iron by duodenal enterocytes causes iron overload which is the hallmark of the disease. Current thinking is that defective Hepcidin synthesis or defective iron-sensing mechanisms leading to Hepcidin deficiency is the cause of iron overload in HFE-Haemochromatosis. Thus HFE-Haemochromatosis has been described as an endocrine disease. Basal levels of Hepcidin appear to be normal in HFE-Haemochromatosis patients. This contradicts current theories of defective Hepcidin synthesis as the cause of Hereditary HFE-Haemochromatosis. We propose that the defect in HFE-Haemochromatosis is the loss of Hepcidin surge in response to intake of dietary iron and is not as a result of reduced synthesis. | 10.1016/j.mehy.2007.10.007 |
pubmed_3_2261 | We recently compared the HCV polyprotein to the human proteome in order to test whether amino acid sequences unique to the virus could represent immunodominant epitopic determinants of the human humoral immune response against HCV. We identified a relatively limited number of HCV fragments with no/low similarity to the human host that represented exclusive HCV motifs. In this study, the peptides corresponding to low/zero similarity sequences were synthesized and assayed with HCV-infected sera. With different patterns, the synthetic HCV peptides corresponding to low/zero similarity sequences were found to be immunoreactive. In particular, the HCV E1 (315-323) HRMAWDMMM, HCV E2/NS1 (547-555) NWFGCTWMN, and HCV NS5 (2638-2646) YDTRCFDST sequences were immunodominant in the HCV-infected cohort under study. These three peptides correspond to sequences that are endowed with low-similarity to the human proteome, are highly conserved among various HCV strains, and have, potentially, a scarce susceptibility to proteolytic attacks. These data may be of help in defining the multiple factors which concur in the modulation of the human immune response against HCV, eventually providing information for the design of effective anti-HCV vaccines. | 10.1007/s00262-008-0456-y |
pubmed_483_4750 | Carbonaceous aerosols are linked to severe haze and health effects, while its origins remain still unclear over China. PM2.5 samples covering four seasons from Jan. 2016 to Jan. 2017 were collected at six sites in Chifeng, a representative agro-pastoral transitional zone of North China focusing on the characteristics and sources of organic carbon (OC) and elemental carbon (EC). The annual averages of OC, EC were 9.00 ± 7.24 μg m-3, 1.06 ± 0.79 μg m-3 with site Songshan in coal mining region exhibited significantly enhanced levels. The residential heating emissions, air stagnation, and secondary organic formation all contributed the higher OC, EC levels in winter. Meanwhile, the impacts from open biomass burning were most intensive in spring. The retroplumes via Lagrangian model highlighted a strong seasonality of regional sources which had more impacts on EC increases. The Positive Matrix Factorization (PMF) model resolved six primary sources, namely, coal combustion, biomass burning, industrial processes, oil combustion, fugitive dust, and fireworks. Coal combustion and biomass burning comprised large fractions of OC (30.57%, 30.40%) and EC (23.26%, 38.47%) across the sites, while contributions of industrial processes and oil combustion clearly increased in the sites near industrial sources as smelters. PMF and EC tracer method gave well correlated (r=0.65) estimates of Secondary OC (SOC). The proportion of coal combustion and SOC were more enhanced along with PM2.5 elevation compared to other sources, suggesting their importances during the pollution events. | 10.1016/j.envpol.2019.03.073 |
pubmed_154_9823 | The effectiveness of two activation techniques, collision activated dissociation (CAD) and infrared multiphoton dissociation (IRMPD), is compared for structural characterization of protonated and lithium-cationized macrolides and a series of synthetic precursors in a quadrupole ion trap (QIT). Generally, cleavage of the glycosidic linkages attaching the sugars to the macrolide ring and water losses constitute the major fragmentation pathways for most of the protonated compounds. In the IRMPD spectra, a diagnostic fragment ion assigned as the desosamine ion is a dominant ion that is not observed in the CAD spectra because of the higher m/z limit of the storage range required during collisional activation. Activation of the lithium-cationized species results in new diagnostic fragmentation pathways that are particularly useful for confirming the identities of the protecting groups in the synthetic precursors. Multi-step IRMPD allows mapping of the fragmentation genealogies in greater detail and supports the proposed structures of the fragment ions. | 10.1016/S1044-0305(02)00366-5 |
pubmed_693_3421 | A case of ergotism is described in a patient with Banti's syndrome in whom a porto-systemic shunt had been made three times. She was admitted to hospital with severe ischaemia of the extremities after having taken a single oral dose of 1 mg ergotamine tartrate. Her condition improved rapidly after 2 to 3 days and the circulation was normal after one week. The possible mechanism of ergotism in this patient is discussed. Although the plasma concentration of ergotamine was not measured, the likeliest explanation was that the serious side effects were related to the altered pharmacokinetics and loss of first-pass metabolism of the drug due to the venous bypass of the liver. | 10.1007/BF00568205 |
pubmed_589_10266 | This study was designed to assess the effect of a dairy-based recovery beverage on post-exercise appetite and energy intake in active females. Thirteen active females completed three trials in a crossover design. Participants completed 60 min of cycling at 65% V̇O2peak, before a 120 min recovery period. On completion of cycling, participants consumed a commercially available dairy-based beverage (DBB), a commercially available carbohydrate beverage (CHO), or a water control (H₂O). Non-esterified fatty acids, glucose, and appetite-related peptides alongside measures of subjective appetite were sampled at baseline and at 30 min intervals during recovery. At 120 min, energy intake was assessed in the laboratory by ad libitum assessment, and in the free-living environment by weighed food record for the remainder of the study day. Energy intake at the ad libitum lunch was lower after DBB compared to H₂O (4.43 ± 0.20, 5.58 ± 0.41 MJ, respectively; p = 0.046; (95% CI: -2.28, -0.20 MJ)), but was not different to CHO (5.21 ± 0.46 MJ), with no difference between trials thereafter. Insulin and GLP-17-36 were higher following DBB compared to H₂O (p = 0.015 and p = 0.001, respectively) but not to CHO (p = 1.00 and p = 0.146, respectively). In addition, glucagon was higher following DBB compared to CHO (p = 0.008) but not to H₂O (p = 0.074). The results demonstrate that where DBB consumption may manifest in accelerated recovery, this may be possible without significantly affecting total energy intake and subsequent appetite-related responses relative to a CHO beverage. | pubmed_589_10266 |
pubmed_665_3296 | OBJECTIVE
The purpose of this study is to examine the relationship between hormone-receptor status and histological parameters, considering that some estrogen receptor (ER)-negative breast carcinoma are suggested to be of myoepithelial origin or differentiation; and to examine the presence of significant difference by myoepithelial markers and define their morphologies.
METHODS
For this research, 30 estrogen receptor-negative and 31 estrogen receptor-positive breast carcinomas diagnosed at the Pathology Department, Istanbul Training and Education Hospital, Istanbul, Turkey, between February 2003 and October 2004 were considered and compared clinically, microscopically and immunohistochemically considering myoepithelial markers using SMA, S100, keratin14.
RESULTS
We found a higher amount of grade 3 frequency pushing margins, solid islets, and presence of central necrosis in the estrogen receptor-negative group than in the positive group (p<0.001 and p<0.05). Six estrogen-negative and 2 estrogen-positive cases were found positive for myoepithelial markers; a difference which is non-significant (p=0.147). The presence of solid islets, fusiform, and clear cells was detected higher in myoepithelial positive tumors than in negative group (p<0.05).
CONCLUSION
For daily pathologic applications, some morphological properties of a breast carcinoma can give clues about ER and myoepithelial features. In estrogen receptor-negative tumors, there is a remarkable myoepithelial marker positivity. Studies involving broader series and different myoepithelial markers could give more reliable results. | pubmed_665_3296 |
pubmed_126_7391 | Diabetic nephropathy is a serious and frequent complication of insulin-dependent diabetes mellitus (IDDM) that has a strong genetic component. Several case-control studies have reported conflicting results with regard to the role of angiotensinogen gene polymorphisms, specifically the M235T T allele, in the development of diabetic nephropathy. The primary limitation of the case-control approach is that bias may be introduced by unrecognized differences in the populations selected for cases and control subjects. In contrast, family-based approaches, such as the transmission/disequilibrium test, assess whether a particular variant, or allele, is transmitted preferentially from a parent having a single copy of that allele. Thus each family provides its own control, thereby eliminating spurious results caused by mismatched population samples. To take advantage of this study design for further investigation of M235T, we collected from the Joslin Diabetes Center in Boston 148 IDDM patients with diabetic nephropathy, 62 nephropathy-free patients with long-duration IDDM, and, very importantly, parents of all these individuals. We found that among males (but not females) the T allele of the M235T polymorphism was transmitted preferentially to those with nephropathy compared with IDDM patients without nephropathy (P=.05). Moreover, the T allele was transmitted preferentially to patients with the most severe manifestation of nephropathy, end-stage renal disease (P=.04). In conclusion, results obtained in our family-based study support a role of the angiotensinogen gene M235T polymorphism, and specifically the T allele, in the development of diabetic nephropathy in IDDM. | 10.1161/01.hyp.31.2.627 |
pubmed_234_3389 | Glutamate is believed to be an excitatory amino acid neurotransmitter in the retina. Enzymes for glutamate metabolism, such as glutamate dehydrogenase, ornithine aminotransferase, glutaminase, and aspartate aminotransferase (AAT), exist mainly in the mitochondria. The abnormal increase of intracellular calcium ions in ischemic retinal cells may cause an influx of calcium ions into the mitochondria, subsequently affecting various mitochondrial enzyme activities through the activity of mitochondrial calpain. As AAT has the highest level of activity among enzymes involved in glutamate metabolism, we investigated the change of AAT activity in ischemic and hypoxic rat retinas and the protection against such activity by calpain inhibitors. We used normal RCS (rdy+/rdy+) rats. For the in vivo studies, we clamped the optic nerve of anesthetized rats to induce ischemia. In the in vitro studies, the eye cups were incubated with Locke's solution saturated with 95% N2/5% CO2. The activity of cytosolic AAT (cAAT) was about 20% of total activity, whereas mitochondrial AAT (mAAT) was about 75% in rat retina. Ninety minutes of ischemia or hypoxia caused a 20% decrease in mAAT activity, whereas cAAT activity remained unchanged. To examine the contribution of intracellular calcium ions to the degradation of mAAT, we used Ca2+-free Locke's solution containing 1 mM EGTA, ryanodine (Ca2+ channel blocker), and thapsigargin (Ca2+-ATPase inhibitor). In the present study, thapsigargin in Ca2+-free Locke's solution, but not ryanodine in this solution, was found to prevent AAT degradation. AAT degradation was also prevented by calpain inhibitors (Ca2+-dependent protease inhibitor) such as calpeptin at 1 nM, 10 nM, 0.1 microM, 1 microM and 10 microM, and by calpain inhibitor peptide, but not by other protease inhibitors (10 microM leupeptin, pepstatin, chymostatin). Additionally, we determined the subcellular localization of calpain activity and examined the change of calpain activity in ischemic rat retinas. Our results suggest that decreased activity of mAAT in ischemic and hypoxic rat retinas might be evoked by the degradation by calpain-catalyzed proteolysis in mitochondria. | 10.1016/s0167-4889(99)00062-2 |
pubmed_161_2355 | Polyvinyl alcohol is rigid foam used in pressed or unpressed form for the purpose of embolisation. It is suitable for both micro-embolisation in the vascular periphery and for central vascular occlusion. Polyvinyl alcohol will result in permanent vascular occlusion. Basing on the experience collected with 71 embolizations, the article reports on the technique applied and on the results obtained with craniofacial, thoracic, abdominal, pelvic and peripheral embolisation. | pubmed_161_2355 |
pubmed_924_4862 | The thymidine analog bromodeoxyuridine (BrdU) is incorporated into newly synthesized DNA and has been shown to increase the susceptibility of incorporating cells to ionizing radiation. However, in the absence of secondary stressors, BrdU is thought to substitute relatively benignly for thymidine and is commonly used to "birth-date" proliferative cells. We report a novel antiproliferative effect of BrdU on cancer cells, which is independent of its role in radiosensitization. A single, brief in vitro exposure to BrdU induces a profound and sustained reduction in the proliferation rate of all cancer cells examined. Cells do not die but variably up-regulate some senescence-associated proteins as they accumulate in the G1 phase of the cell cycle. Bromodeoxyuridine also impairs the proliferative capacity of primary tumor-initiating human glioma cells and may therefore represent a means of targeting cancer stem cells. Finally, conservative in vivo BrdU regimens--in the absence of any other treatment--significantly suppress the progression of gliomas in the highly aggressive, syngeneic RG2 model. These results suggest that BrdU may have an important role as an adjunctive therapeutic for a wide variety of cancers based on new insights into its effect as a negative regulator of cell cycle progression. | 10.1593/neo.08382 |
pubmed_71_15396 | PROBLEM AND BACKGROUND
Vaginal birth after caesarean section is a safe option for the majority of women. Seeking women's views can be of help in understanding factors of importance for achieving vaginal birth in countries where the vaginal birth rates after caesarean is low.
AIM
To investigate women's views on important factors to improve the rate of vaginal birth after caesareanin countries where vaginal birth rates after previous caesarean are low.
METHODS
A qualitative study using content analysis. Data were gathered through focus groups and individual interviews with 51 women, in their native languages, in Germany, Ireland and Italy. The women were asked five questions about vaginal birth after caesarean. Data were translated to English, analysed together and finally validated in each country.
FINDINGS
Important factors for the women were that all involved in caring for them were of the same opinion about vaginal birth after caesarean, that they experience shared decision-making with clinicians supportive of vaginal birth, receive correct information, are sufficiently prepared for a vaginal birth, and experience a culture that supports vaginal birth after caesarean.
DISCUSSION AND CONCLUSION
Women's decision-making about vaginal birth after caesarean in these countries involves a complex, multidimensional interplay of medical, psychosocial, cultural, personal and practical considerations. Further research is needed to explore if the information deficit women report negatively affects their ability to make informed choices, and to understand what matters most to women when making decisions about vaginal birth after a previous caesarean as a mode of birth. | 10.1016/j.wombi.2017.04.009 |
pubmed_827_6318 | To obtain a better understanding of the olfactory processes that allow mosquitoes to identify human hosts, a molecular study has been performed to identify and characterize molecules in the olfactory signalling pathway of the African malaria vector Anopheles gambiae. Using cDNA libraries from antennae of females and males, a collection of cDNAs encoding odorant binding proteins and other novel antennal proteins were isolated and characterized, which represent various families of putative carrier proteins with homologues in other insects. Using filter array hybridizations and quantitative RT PCR, regulation and gender specificity of expression of these genes was investigated. Significant differences in steady-state levels of some of these putative carrier protein genes were detected between the sexes and after blood feeding in females. | 10.1046/j.1365-2583.2003.00443.x |
pubmed_114_4579 | Legionnaires' disease occurred in a 3-year-old boy with Down's syndrome. His illness was characterized by bilateral pneumonia, high fever, and response to erythromycin. The diagnosis was made by demonstrating Legionella pneumophila, serogroup 1, in sputum with a direct fluorescent antibody stain. L pneumophila antigen was detected in urine by an enzyme-linked immunospecific assay. The diagnosis was confirmed by a more than fourfold rise in serum antibody titer. Although Legionnaires' disease appears to be uncommon in children, it should be included in the differential diagnosis of pneumonia in the immunocompromised child. | pubmed_114_4579 |
pubmed_625_7176 | BACKGROUND
This study compared the timing, regulatory marketing authorization decisions, and the final labeling for products submitted to Swissmedic to those submitted to European Medicines Agency (EMA) and the US Food & Drug Administration (FDA).
METHODS
The Centre for Innovation in Regulatory Science (CIRS) conducted an analysis of a representative cohort of 63 new molecular entities (NMEs) that were submitted to Swissmedic from 2006 through 2010 and that were also submitted to, and approved by, the EMA centralized procedure and FDA. Parameters considered included the outcome and timing of regulatory marketing authorization decisions and the comparison of each product's Summary of Product Characteristics (SPC) from the 3 agencies. The results were presented at the Swissmedic 10th Anniversary Symposium, "The Challenges of Regulation and Changing Regulations Paradigms," and they form the basis of this article.
RESULTS
The median approval times for these NMEs were longer for Swissmedic (480 days) compared with FDA (303 days) and EMA (416 days). However, if an expedited application review procedure (a "priority review" [FDA], "accelerated assessment" [EMA], or "accelerated review" [Swissmedic]) was applied, Swissmedic was faster (207 days) than EMA (300 days) and essentially as fast as FDA (229 days). The main differences were in the nature of the wording of parts of the initial SPC, particularly the "Contraindications" and "Special warnings and precautions" for FDA and "Special warnings and precautions" for EMA.
CONCLUSIONS
Results suggest there is no clear evidence that Swissmedic was substantially different in its initial regulatory decisions or SPC recommendations compared with the EMA or FDA. | 10.1177/2168479016655841 |
pubmed_890_2991 | This study aimed to unravel the molecular mechanism of oral squamous cell carcinoma (OSCC). With microarray dataset GSE30784, differentially expressed genes (DEGs) were identified between OSCC and control samples. The DEGs overlapped with genes obtained from online database MalaCards were determined as OSCCDEG, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. A total of 5177 up-regulated and 6081 down-regulated DEGs were identified between OSCC and control. Out of the DEGs, 451 genes were overlapped with the 704 genes gained from MalaCards and regarded as "OSCCDEG". Up-regulated OSCCDEG were associated with cell cycle pathway, while down-regulated OSCCDEG were linked to ErbB pathway. ANGPT1, ANGPT2 and 3 hub proteins (EGFR, HSP90AA1, RB1) in the PPI network were associated with the survival rates of several tumors. The largest network module with the hub protein EGFR was associated with positive regulation of cell communication. The second largest module with the hub node FN1 was related to angiogenesis. For the third network module in connection with DNA metabolism, the hub protein was PCNA. ErbB and cell cycle pathways were crucial for OSCC. EGFR, FN1, PCNA, ANGPT1 and ANGPT2 might be potential biomarkers for OSCC. These findings help provide guidelines for treating OSCC. | 10.4149/neo_2017_201 |
pubmed_125_22975 | Intimate partner violence (IPV) and sexual violence (SV) are drivers of women's morbidity and mortality yet remain among the most underreported crimes in the United States. Understanding IPV/SV survivors' justice preferences and justice definitions can strengthen violence prevention and response systems. In-depth interviews were conducted with women who experienced past-year IPV (n = 26), to explore their justice preferences and recommendations. Primary themes included accountability, safety, and rehabilitation, with examples within and outside the current justice system, and across restorative and retributive justice frameworks. Women sought accountability through a variety of means. Retributive approaches like incarceration offered accountability as well as fleeting safety, but were critically limited in addressing the root causes of violence and, in some cases, were felt to exacerbate the problem. Women's expressed needs and preferences centered on restorative aspects of justice, including perpetrator's acknowledgment of harm, achieving physical safety and stability, and perpetrator rehabilitation through counseling. Paradoxically, women's safety-related justice goals both encouraged and discouraged their engagement in the formal justice system. The discordance between women's justice preferences and their perceptions and experiences within the current justice system illustrate complex and difficult trade-offs faced by survivors in achieving physical, social, and economic safety. Moreover, they likely contribute to the low levels of IPV/SV reporting to police. Women's goals were aligned with restorative justice principles, illustrating the value of this approach. In an era of unprecedented dialogue on justice reform, results provide direction for integrating restorative justice practices to strengthen the justice response to violence against women. | 10.1177/0886260520943728 |
pubmed_1069_3213 | A manganese-dependent 3,4-dihydroxyphenylactate 2,3-dioxygenase from Arthrobacter globiformis strain CM-2 (MndD) cloned in Escherichia coli has been purified to homogeneity. Sedimentation equilibrium analysis indicates an alpha 4 homotetrameric holoenzyme structure (4 x 38,861 Da). Steady-state kinetic analysis of MndD with a variety of substrates and inhibitors yields very similar relative rates to the known Fe(II)- and Mn(II)-dependent 3,4-dihydroxyphenylacetate 2,3-dioxygenases from Pseudomonas ovalis and Bacillus brevis, respectively. Yet, unlike the Fe(II)-dependent enzyme, MndD retains almost all activity in the presence of H2O2 and CN- and is inactivated by Fe(II). ICP emission analysis confirms the presence of 3.0 +/- 0.2 g-atoms Mn (and only 0.7 +/- 0.2 g-atoms Fe) per tetrameric holoenzyme molecule. Comparison of MndD samples with varying metal content, including an apo and partial-apo enzyme preparation, shows a strong positive correlation between specific activity and Mn content. EPR spectra of MndD as isolated exhibit a nearly isotropic g = 2.0 signal having 6-fold hyperfine splitting (A = 95 G) typical of octahedrally coordinated Mn(II) in a protein. Quantitation of the EPR spin yields 3.4 +/- 0.3 g-atoms of Mn(II) per holoenzyme. When exposed anaerobically to its natural substrate, 3,4-dihydroxyphenylacetate (3,4-DHPA), the EPR spectrum undergoes a dramatic change characterized by the attenuation of the g = 2 signal and the appearance of new signals at g = 1.2, 2.9, 4.3, and 16. The g = 4.3 signal displays 6-fold hyperfine splitting (A = 95 G) that unambiguously assigns it to the Mn(II) center. The appearance of these new signals indicates a large increase in zero-field splitting suggestive of a change in ligand coordination to the Mn(II) center. Similarly perturbed signals are seen in the EPR spectra of MndD complexed with the comparably active substrate analog, D,L-3,4-dihydroxymandelate, or the tight-binding inhibitor, p-nitrocatechol, but not in the complexes with weaker binding substrates and inhibitors. The fact that only strong-binding substrates and inhibitors significantly perturb the Mn(II) EPR signal strongly suggests that the substrate coordinates to the Mn(II) center in the catalytic pathway. | 10.1021/bi951979h |
pubmed_486_8603 | We discuss large animal translational models of arrhythmia susceptibility and sudden cardiac death, focusing on important considerations when interpreting the data derived before applying them to human trials. The utility of large animal models of arrhythmia and the pros and cons of specific translational large animals used will be discussed, including the necessary tradeoffs between models designed to derive mechanisms vs. those to test therapies. Recent technical advancements which can be applied to large animal models of arrhythmias to better elucidate mechanistic insights will be introduced. Finally, some specific examples of past successes and challenges in translating the results of large animal models of arrhythmias to clinical trials and practice will be examined, and common themes regarding the success and failure of translating studies to therapy in man will be discussed. | 10.3389/fcvm.2019.00135 |
pubmed_239_14032 | BACKGROUND
Aspirin has antipyretic and anti-inflammatory properties and is frequently used by pregnant and lactating women. However, its transfer in human milk when administered at low dose has not been reported. Research aim: This study aimed to evaluate the transfer of acetylsalicylic acid and its metabolite, salicylic acid, into human milk following the use of low dose aspirin.
METHODS
In this study, milk samples were collected at 0, 1, 2, 4, 8, 12, and 24 hours from seven breastfeeding women after a steady-state daily dose of 81 mg of aspirin. Milk levels of acetylsalicylic acid and salicylic acid were determined by liquid chromatography-tandem mass spectrometry.
RESULTS
Acetylsalicylic acid levels were below the limit of quantification (0.61 ng/ml) in all the milk samples, whereas salicylic acid was detected at very low concentrations. The average concentration of salicylic acid observed was 24 ng/ml and the estimated relative infant dose was 0.4%.
CONCLUSION
Acetylsalicylic acid transfer into milk is so low that it is undetectable even by highly sophisticated methodology. Salicylic acid does appear in the human milk in comparatively low amounts, which are probably subclinical in infants. Thus, the daily use of an 81-mg dose of aspirin should be considered safe during lactation. | 10.1177/0890334417695207 |
pubmed_615_15325 | Cladistics is a biological philosophy that uses genealogical relationship among species and an inferred sequence of divergence as the basis of classification. This review critically surveys the chronological development of biological classification from Aristotle through our postgenomic era with a central focus on cladistics. In 1957, Julian Huxley coined cladogenesis to denote splitting from subspeciation. In 1960, the English translation of Willi Hennig's 1950 work, Systematic Phylogenetics, was published, which received strong opposition from pheneticists, such as numerical taxonomists Peter Sneath and Robert Sokal, and evolutionary taxonomist, Ernst Mayr, and sparked acrimonious debates in 1960-1980. In 1977-1990, Carl Woese pioneered in using small subunit rRNA gene sequences to delimitate the three domains of cellular life and established major prokaryotic phyla. Cladistics has since dominated taxonomy. Despite being compatible with modern microbiological observations, i.e. organisms with unusual phenotypes, restricted expression of characteristics and occasionally being uncultivable, increasing recognition of pervasiveness and abundance of horizontal gene transfer has challenged relevance and validity of cladistics. The mosaic nature of eukaryotic and prokaryotic genomes was also gradually discovered. In the mid-2000s, high-throughput and whole-genome sequencing became routine and complex geneologies of organisms have led to the proposal of a reticulated web of life. While genomics only indirectly leads to understanding of functional adaptations to ecological niches, computational modeling of entire organisms is underway and the gap between genomics and phenetics may soon be bridged. Controversies are not expected to settle as taxonomic classifications shall remain subjective to serve the human scientist, not the classified. | 10.1007/s13238-013-3050-9 |
pubmed_82_7439 | The objectives of this study was to compare electrovaporization (EVAP) of the prostate to transurethral resection of the prostate (TURP). A prospective evaluation of 60 patients treated for benign prostatic hypertrophy (BPH) was carried out between November 1994 and November 1996. Twenty five patients were treated with TURP and 35 patients with EVAP. All patients had a minimum 12 month follow-up. The results obtained were comparable in terms of surgical procedure time with a bloodless surgical field using EVAP. EVAP was advantageous in reducing the time with indwelling urinary catheter postoperatively and reducing hospital stay. At 12 month follow-up results of flow rates and symptom scores were similar for both TURP and EVAP. Reoperation rate for residual BPH in the EVAP group was higher than for TURP, suggesting that EVAP should probably be limited to smaller sized glands. This study suggests that EVAP is a viable alternative to TURP in selected patients. It requires no specialized equipment and may allow a reduction in catheterization and hospital stay. | pubmed_82_7439 |
pubmed_279_19115 | We previously reported monoclonal antibodies (MAbs) specific to S. typhi 52 kDa antigen which do not cross react with related protein antigens from 11 bacteria causing enteric fever and enteric fever-like illness. Using the combination of these specific MAbs and recombinant DNA technology, expression plasmids containing the antigen gene producing substantial amount of the S. typhi protein antigen have been established. Plasmid pSKM-T7 containing the specific 52 kDa antigen gene was cloned and the antigen expressed was detectable by immunoblotting using specific mAbs. The complete nucleotide sequence of this gene was compared with other bacterial sequences and found to be highly homologous with the flagellin gene H1-d of S. muenchen except in the hypervariable region in the central portion. The specific 52 kDa antigen of S. typhi detected by our MAbs is thus a flagellin. | pubmed_279_19115 |
pubmed_871_12883 | The NADH methemoglobin-reductase (EC 1.6.2.2) is mainly responsible for the maintenance of hemoglobin in its reduced and active state. The present study reveals the comparative status of this enzyme in normal Beagle dogs, rats, mice, mastomys and hamsters erythrocytes. The spectrophotometric and electrophoretic determinations showed that the above mentioned enzyme was deficient in the Beagle dog's erythrocytes. Furthermore, in vitro studies on the sensitivity of these rodents and Beagle dogs hemolysate towards oxidants, like primaquine and sodium nitrate, depicted a higher level of methemoglobin formation in the Beagle dogs hemolysate as compared to that of the rodent species. The deficiency of methemoglobin reductase in Beagle dogs erythrocytes could be responsible for their increased sensitivity towards oxidant induced methemoglobinemia. | 10.1023/a:1014853421871 |
pubmed_868_15357 | OBJECTIVE
To estimate the effect of age, period and birth cohort on mortality from breast cancer in Brazil and regions.
METHODS
Data on mortality from breast cancer were analyzed for women aged > 30 years in Brazil and regions from 1980 to 2009. The effect of age, period, and birth cohort was calculated by Poisson regression model using estimable functions: deviations, curvatures and drift through the Epi library of R statistical software version 3.2.1.
RESULTS
The mean mortality rate for the period was 22.3 per 100 000 women in Brazil. The highest rate was 32.4 deaths per 100 000 women in the South, and the lowest, 8.6 deaths per 100 000 women in the North. The analysis of birth cohorts showed a progressive increase in the risk of death in women born after the 1930s, except in the Southeast, where a decrease in relative risk was noted for this group.
CONCLUSIONS
The analyses revealed a reduction in the risk of death from breast cancer in Brazil and in most regions for birth cohorts starting in the 1930s, and an increased in the risk of death starting in the 1990s until the period from 2000 to 2005. | pubmed_868_15357 |
pubmed_624_16694 | The role of histamine in brain function is discussed. A brief review is presented on the three types of histamine receptors with regard to their biochemistry and functions, as well as on specific ligands, both agonists and antagonists. It is concluded that several aspects of the pharmacology of histamine in the central nervous system are still a matter of empirism and speculations. The recent publications on the brain-penetrating H2 antagonist zolantidine and the selective H3 agonists and antagonists are expected to contribute to the knowledge of the histaminergic pathways in the brain. Therapeutical areas within the central nervous system are related to behaviour (including wake-sleep), neuroendocrinal processes, the control of muscle activity and cerebral circulation. | 10.1007/BF01959461 |
pubmed_847_4115 | INTRODUCTION
Ubiquitin-specific protease 7 (USP7) plays a critical role in multiple signaling pathways, and many recent studies have proved its association with many diseases. The USP7-murine double minute 2-p53 pathway and the relationship between USP7 and the important immune protein PD-L1 in cancer progression and metastasis have been clarified. Recently, USP7 has emerged as a promising and potent therapeutic target for cancer and has attracted both academic and industrial attention.
AREAS COVERED
This review focuses on the structure, activity, and applications of USP7 inhibitors in cancer therapy. It also focuses on patents reported since 2014.
EXPERT OPINION
Recently, USP7 has attracted considerable attention owing to its physiological and pathophysiological roles in cancer progression, and few studies have focused on the development of USP7 inhibitors. Compared with micromolar first-generation USP7 inhibitors, second-generation USP7 inhibitors exhibit higher potency (at nanomolar level for both USP7 and cell inhibitory activities), higher selectivity, and better pharmacokinetic properties, and they largely broaden the range of candidates for further clinical tests. However, there is still a need for a more precise description of compounds with receptors, the structural diversity of these compounds, and screening methods. | 10.1080/13543776.2022.2058873 |
pubmed_630_2694 | Current combinations of antiretroviral drugs for the treatment of HIV infection can successfully achieve and maintain long-term suppression of HIV-1 replication in plasma. Still, none of these therapies is capable of eradicating the virus from the long-lived cellular reservoir that represents the major barrier to HIV cure. | pubmed_630_2694 |
pubmed_475_4710 | A recent flurry of reports correlates replication timing (RT) with mutation rates during both evolution and cancer. Specifically, point mutations and copy number losses correlate with late replication, while copy number gains and other rearrangements correlate with early replication. In some cases, plausible mechanisms have been proposed. Point mutation rates may reflect temporal variation in repair mechanisms. Transcription-induced double-strand breaks are expected to occur in transcriptionally active early replicating chromatin. Fusion partners are generally in close proximity, and chromatin in close proximity replicates at similar times. However, temporal enrichment of copy number gains and losses remains an enigma. Moreover, many conclusions are compromised by a lack of matched RT and sequence datasets, the filtering out of developmental variation in RT, and the use of somatic cell lines to make inferences about germline evolution. | pubmed_475_4710 |
pubmed_311_18415 | Osteosarcoma (OS) is the commonest malignant bone tumor in the world. High incidence of OS has gradually become a social problem. Recent years, numerous studies have revealed that long non-coding RNAs (lncRNAs) are crucial regulators in the tumor progression. As a member of lncRNA family, MIR100HG has been reported to be an oncogene in breast cancer and acute megakaryoblastic leukemia. Nevertheless, the specific role of MIR100HG in osteosarcoma is still unclear. In this study, we investigated the biological function and molecular mechanism of MIR100HG in the progression of osteosarcoma. At first, we measured the high expression of MIR100HG in OS tissues and cell lines by qRT-PCR. Kaplan-Meier method revealed that high expression of MIR100HG is a factor for the poor prognosis of OS patients (P = 0.004). To explore the effect of MIR100HG on the biological processes of OS, loss-of-function assays were conducted in OS cells. Functionally, MIR100HG knockdown suppressed cell proliferation, cell cycle progression while promoted cell apoptosis. Mechanistically, MIR100HG was upregulated by the transcription factor ELK1. The upregulation of MIR100HG led to the inactivation of Hippo pathway. Furthermore, we found that MIR100HG inactivated Hippo pathway in OS cells by epigenetically silencing LATS1 and LATS2. Rescue assays demonstrated that LATS1/2 involved in MIR100HG-mediated OS progression. In summary, our study indicated that ELK1-induced upregulation of MIR100HG promoted OS progression by epigenetically silencing LATS1 and LATS2 and inactivating Hippo pathway. | 10.1016/j.biopha.2018.10.029 |
pubmed_416_20791 | Acute lung injury is marked by damage to alveolar-capillary barrier. High pulmonary levels of matrix-degrading serine proteinase trypsin and matrix metalloproteinases (MMP)-2, -8, and -9 have been shown in preterm infants with respiratory distress syndrome (RDS). We studied expression of trypsin and MMP-2, -8, and -9 in rats exposed to >95% oxygen for 24, 48, or 60 h. As demonstrated by zymography and Western immunoblotting, levels of trypsin and MMP-2, -8, and -9 in bronchoalveolar lavage fluid (BALF) sharply increased after 48 h of hyperoxia relative to normoxia controls. This coincided with increase in alveolar-capillary permeability, as indicated by increased protein concentration in BALF. Both neutrophil-derived 80-kD and mesenchymal cell-derived 60-kD MMP-8 isoforms were detected in BALF. Of them, mesenchymal-type MMP-8 predominated. In immunohistochemistry, alveolar epithelium showed strong trypsin expression at 48 and 60 h of hyperoxia, whereas it was predominantly negative in controls. MMP-8 was mostly expressed in macrophages. Marked up-regulation of trypsin and MMP-8 early during hyperoxic lung injury suggests that these enzymes play a role in the pathogenesis of acute lung injury and may therefore be potential targets for therapy of lung injury. | 10.1203/01.pdr.0000238342.16081.f9 |
pubmed_142_19328 | A target sound can become more audible and may "pop out" from a simultaneously presented masker if the masker is presented first by itself, as a precursor. This phenomenon, known as auditory enhancement, may reflect the general perceptual principle of contrast enhancement, which facilitates adaptation to ongoing acoustic conditions and the detection of new events. Little is known about the mechanisms underlying enhancement, and potential confounding factors have made the size of the effect and its time course a point of contention. Here we measured enhancement as a function of precursor duration and delay between precursor offset and target onset, using 2 single-interval pitch comparison tasks, which involve either same-different or up-down judgments, to avoid the potential confounds of earlier studies. Although these 2 tasks elicit different levels of performance and may reflect different underlying mechanisms, they produced similar amounts of enhancement. The effect decreased with decreasing precursor duration, but remained present for precursors as short as 62.5 ms, and decreased with increasing gap between the precursor and target, but remained measurable 1 s after the precursor. Additional conditions, examining the effect of precursor/masker similarity and the possible role of grouping and cueing, suggest multiple sources of auditory enhancement. | 10.1037/xhp0000115 |
pubmed_150_3301 | OBJECTIVE
To develop and describe a technique for percutaneous radiologic gastrojejunostomy tube placement in the dog.
DESIGN
Prospective technique development study.
SETTING
University teaching hospital.
ANIMALS
Six healthy adult male Beagles.
INTERVENTIONS
Following anesthetic induction, fluoroscopic and ultrasound guidance were used to identify an appropriate gastropexy site on the left lateral abdomen. Gastropexy was performed using gastrointestinal suture anchors. An over-the-wire catheter technique using fluoroscopic guidance was used to achieve jejunal access. An 18F/8F, 58 cm, dual-lumen gastrojejunal feeding tube was placed via serial over-the-wire dilation of the body wall using an 18F peel-away introducer kit. Tube location was determined radiographically immediately following placement and on days 2, 4, after emesis on day 4, and at time of gastrojejunal feeding tube removal (day 16-18).
MEASUREMENTS AND MAIN RESULTS
Percutaneous radiologic gastrojejunostomy (PRGJ) tube placement was successful in all dogs. Median time to pyloric passage with the guide wire was 23.5 minutes (range, 9-93 minutes). Median total procedure time was 53 minutes (range, 49-113 minutes). Significant tube migration was not observed at any point during the study. One dog developed linear foreign body obstruction secondary to the tube on day 5 that was relieved by release of the jejunal component. Other complications were minor and included mild-to-moderate peristomal inflammation in all dogs and removal of the feeding tube on day 3 by 1 dog. Feedings were well tolerated in all dogs.
CONCLUSIONS
PRGJ tube placement in the dog is a safe and minimally invasive technique that allows for jejunal feeding without surgery or endoscopy. The high success rates, acceptable procedural times, and minimal complications are appealing for use in critically ill patients. Although additional evaluations are needed, PRGJ tube placement may be considered for dogs that require postpyloric feeding with or without gastric decompression. | 10.1111/vec.12506 |
pubmed_22_14056 | AIM
To provide evidence regarding the postoperative treatment of patients with T4bN1-3M0/TxN3bM0 gastric cancer, for which guidelines have not been established.
METHODS
Patients who had undergone curative resection between 1996 and 2014 with a pathological stage of T4bN1-3M0/TxN3bM0 for gastric cancer were retrospectively analyzed; staging was based on the 7th edition of the American Joint Committee on Cancer staging system. The clinicopathological characteristics, administration of adjuvant chemotherapy, and patterns of recurrence were studied. Univariate and multivariate analyses of prognostic factors were conducted. The chemotherapeutic agents mainly included fluorouropyrimidine, platinum and taxanes, used as monotherapy, doublet, or triplet regimens. Patterns of first recurrence were categorized as locoregional recurrence, peritoneal dissemination, or distant metastasis.
RESULTS
The 5-year overall survival (OS) of the whole group (n = 176) was 16.8%, and the median OS was 25.7 mo (95%CI: 20.9-30.5). Lymphovascular invasion and a node positive rate (NPR) ≥ 0.8 were associated with a poor prognosis (P = 0.01 and P = 0.048, respectively). One hundred forty-seven (83.5%) of the 176 patients eventually experienced recurrence; the most common pattern of the first recurrence was distant metastasis. The prognosis was best for patients with locoregional recurrence and worst for those with peritoneal dissemination. Twelve (6.8%) of the 176 patients did not receive adjuvant chemotherapy, while 164 (93.2%) patients received adjuvant chemotherapy. Combined chemotherapy, including doublet and triplet regimens, was associated with a better prognosis than monotherapy, with no significant difference in 5-year OS (17.5% vs 0%, P = 0.613). The triplet regimen showed no significant survival benefit compared with the doublet regimen for 5-year OS (18.5% vs 17.4%, P = 0.661). Thirty-nine (22.1%) patients received adjuvant chemotherapy for longer than six months; the median OS in patients who received adjuvant chemotherapy for longer than six months was 40.2 mo (95%CI: 30.6-48.2), significantly longer than the 21.6 mo (95%CI: 19.1-24.0) in patients who received adjuvant chemotherapy for less than six months (P = 0.001).
CONCLUSION
Patients with T4bN1-3M0/TxN3bM0 gastric cancer showed a poor prognosis and a high risk of distant metastasis. Adjuvant chemotherapy for longer than six months improved outcomes for them. | 10.4251/wjgo.v10.i1.31 |
pubmed_794_4806 | Fungi belonging to the genus Trichoderma have received much attention in recent years due to their beneficial effects on crop health and their use as pest control agents. Trichoderma activates direct plant defenses against phytophagous arthropods and reinforces indirect plant defense through the attraction of predators. Although the plant defenses against insect herbivores were demonstrated in laboratory experiments, little attention has been paid to the use of Trichoderma spp. in open field conditions. In the present study, we investigated the effects of the inoculation of the commercial Trichoderma harzianum strain T22 on the arthropod community associated with tomato plants and on the crop performance in an experimental field located in South Italy. Our results showed that inoculation with T. harzianum could alter the arthropod community and reduce the abundance of specific pests under field conditions with respect to the sampling period. The present study also confirmed the beneficial effect of T. harzianum against plant pathogens and on tomato fruit. The complex tomato-arthropod-microorganism interactions that occurred in the field are discussed to enrich our current information on the possibilities of using Trichoderma as a green alternative agent in agriculture. | 10.3390/insects13050418 |
pubmed_911_20544 | The aim of this study was to highlight the important stages of the evolution of limb amputation through the ages through the search of the relevant international literature. Limb amputation is one of the most serious surgical operations, which is associated with high mortality and morbidity. Evidence regarding the execution of limb amputation can be found back in Neolithic times. The most important steps in the evolution of the technique of limb amputation were made in the 16th, 17th, and 18th centuries when A. Pare' introduced the vessel ligation and the French barber surgeon Morell introduced the use of a tourniquet to reduce the bleeding. During the same period, from the ''one-stage circular cut'' the technique evolved to either ''three-stage circular cut'' or to ''flap amputation'', single or double. Limb amputation represents one of the oldest and most serious surgical operations. Its evolution parallels the maturation process of surgery, with the major developments in the technique to have been made from the 16th to the 18th century. In the beginning of the 21st century, limb amputation appears to be a safe operation ending up with a functional stump. | pubmed_911_20544 |
pubmed_6_7035 | Autism spectrum disorder (ASD) is a complex set of neurodevelopmental pathologies characterized by impoverished social and communicative abilities and stereotyped behaviors. Although its genetic basis is unquestionable, the involvement of environmental factors such as exposure to pesticides has also been proposed. Despite the systematic analyses of this relationship in humans, there are no specific reviews including both human and preclinical models. The present systematic review summarizes, analyzes, and discusses recent advances in preclinical and epidemiological studies. We included 45 human and 16 preclinical studies. These studies focused on Organophosphates (OP), Organochlorine (OC), Pyrethroid (PT), Neonicotinoid (NN), Carbamate (CM), and mixed exposures. Preclinical studies, where the OP Chlorpyrifos (CPF) compound is the one most studied, pointed to an association between gestational exposure and increased ASD-like behaviors, although the data are inconclusive with regard to other ages or pesticides. Studies in humans focused on prenatal exposure to OP and OC agents, and report cognitive and behavioral alterations related to ASD symptomatology. The results of both suggest that gestational exposure to certain OP agents could be linked to the clinical signs of ASD. Future experimental studies should focus on extending the analysis of ASD-like behaviors in preclinical models and include exposure patterns similar to those observed in human studies. | 10.3390/ijerph18105190 |
pubmed_856_23176 | Pseudarthrosis is a feared complication of spinal fusion procedures. Currently, the gold standard in prevention or treatment of pseudarthrosis is placement of nonvascularized iliac crest bone autograft. While rates of fusion are significantly higher in patients with use of nonvascularized bone autografts than with allografts, patients who have previously failed lumbar arthrodesis or those at a high risk for pseudarthrosis may benefit from a more robust, vascularized bone graft with enhanced osteogenicity. In this article, we discuss the use of iliac crest vascularized bone grafts as an adjunct for high-risk patients undergoing lumbosacral spine arthrodesis. | 10.1055/s-0041-1725986 |
pubmed_315_19266 | The relation of cardiac troponin-I (cTnI) to clinical outcomes was examined in patients with decompensated heart failure and concomitant acute coronary syndrome enrolled into the Randomized Intravenous TeZosentan 4 (RITZ-4) study. RITZ-4 was a multicenter, randomized, double-blind, placebo-controlled trial of the endothelin receptor antagonist tezosentan in patients admitted with acute heart failure and concomitant acute coronary syndrome. One hundred ninety-two patients were enrolled in this study. Patients with baseline cTnI values were included in this analysis, and the relation between cTnI and the composite clinical primary end point of RITZ-4 was evaluated. | 10.1016/j.amjcard.2004.02.051 |
pubmed_36_7087 | Doxazosin, a commonly prescribed treatment for patients with benign prostatic hyperplasia, serves as an α1-blocker of the adrenergic receptors. In this study, we calculated its effect on the ovarian carcinoma cells. Doxazosin induces dose-dependent growth suppression and is additively activated through IFN-α or IFN-γ stimulation. They both enhanced G1 phase arrest, as well as the activity of caspase-3, and the reduction of cyclin D1 and CDK4 protein levels. Doxazosin growth suppression was abolished either by the Janus family of tyrosine kinase (JAK) or the signal transducer and activator of transcription (STAT) inhibitor treatment. The activity of JAK/STAT was dependent on the level of doxazosin, suggesting a requirement of doxazosin for the activation of JAK/STAT. Furthermore, doxazosin plus IFN-α or doxazosin plus IFN-γ additively suppressed the activation of the JAK/STAT signals through phosphorylation of JAK and STAT, thus affecting the activation of subsequent downstream signaling components PI3K, mTOR, 70S6K, and PKCδ. In vivo study demonstrated that doxazosin significantly suppressed tumor growth in an ovarian cancer cell xenograft mouse model, inducing apoptotic cell death by up-regulating the expression of p53, whereas c-Myc expression was markedly reduced. Our data indicate that doxazosin can modulate the apoptotic effects of IFN-α- and IFN-γ through the JAK/STAT signaling pathways. Collectively, we indicate that this action may be a potent chemotherapeutic property against ovarian carcinoma. | 10.18632/genesandcancer.37 |
pubmed_134_2948 | The role of protein kinase C (PKC) isoforms in the neural cell adhesion molecule (NCAM)-mediated neurite outgrowth was tested using a co-culture system consisting of fibroblasts with or without NCAM expression upon which either primary cerebellar granular neurones (CGN) or pheochromocytoma (PC12-E2) cells were grown. The latter transiently expressed various PKC isoforms and domains derived from selected PKCs. PKC inhibitors of various specificity inhibited NCAM-stimulated neuritogenesis from CGN, indicating that PKC is involved in this process. Moreover, stimulation by the NCAM-mimetic peptide, C3d, elicited phosphorylation of PKC in CGN. Expression of kinase-deficient forms of PKCalpha, betaI and betaII blocked NCAM-mediated neurite extension, but had no effect on nerve growth factor (NGF)-mediated neurite outgrowth. Expression of two PKCepsilon constructs: (i) a fragment from PKCepsilon encompassing the pseudosubstrate, the C1a domain (including the actin-binding site, ABS), and parts of the V3 region, or (ii) the PKCepsilon-specific ABS blocked NCAM-mediated neurite extension in both cases. These two constructs also partially inhibited NGF-stimulated neuritogenesis indicating that PKCepsilon is a positive regulator of both NCAM- and NGF-mediated differentiation. We suggest that PKCepsilon is a common downstream mediator for several neuritogenic factors, whereas one or more conventional PKCs are specifically involved in NCAM-stimulated neurite outgrowth. | 10.1111/j.1471-4159.2004.02919.x |
pubmed_983_23152 | Hibernating mammals cease feeding during the winter and rely primarily on stored lipids to fuel alternating periods of torpor and arousal. How hibernators manage large fluxes of lipids and sterols over the annual hibernation cycle is poorly understood. The aim of this study was to investigate lipid and cholesterol transport and storage in ground squirrels studied in spring, summer, and several hibernation states. Cholesterol levels in total plasma, HDL and LDL particles were elevated in hibernators compared with spring or summer squirrels. Hibernation increased plasma apolipoprotein A-I expression and HDL particle size. Expression of cholesterol 7 alpha-hydroxylase was 13-fold lower in hibernators than in active season squirrels. Plasma triglycerides were reduced by fasting in spring but not summer squirrels. In hibernators plasma β-hydroxybutyrate was elevated during torpor whereas triglycerides were low relative to normothermic states. We conclude that the switch to a lipid-based metabolism during winter, coupled with reduced capacity to excrete cholesterol creates a closed system in which efficient use of lipoproteins is essential for survival. | 10.1371/journal.pone.0029111 |
pubmed_506_23032 | OBJECTIVE
Use a standardized system to code parent-child interactions during respiratory treatments for cystic fibrosis (CF) and analyze relations between behaviors during treatments and medical regimen adherence.
METHODS
A total of 15 families (53% girls; M age = 8.9 years; SD = 1.8) had three respiratory treatments recorded in the home environment and coded. Families provided six 24-hr recalls of child medical regimen activities, and electronic airway clearance time was recorded over 3 months to measure medical regimen adherence.
RESULTS
Parent positive attention, instructions, and avoidance of negative statements were significantly related to child cooperation during respiratory treatments. Parental presence, positive attention, instructions, and child cooperation during treatments were related to higher respiratory adherence rates.
CONCLUSIONS
Direct observation methodology has led to effective nutritional adherence intervention for children with CF. These preliminary data demonstrate that an observational method could also be used to develop interventions to promote respiratory medication adherence. | 10.1093/jpepsy/jsu074 |
pubmed_934_14609 | The aim of this study is to estimate the frequency of pathologic complete response (pCR) after neoadjuvant treatment with cisplatin chemotherapy in women with breast cancer and a BRCA1 mutation. One hundred and seven women with breast cancer and a BRCA1 mutation, who were diagnosed with stage I to III breast cancer between December 2006 and June 2014, were treated with cisplatin 75 mg/m(2) every 3 weeks for four cycles, followed by mastectomy and conventional chemotherapy. Information was collected on clinical stage, grade, hormone receptor status, and Her2neu status prior to treatment. pCR was determined by review of surgical specimens. One hundred and seven patients were enrolled in the study, including 93 patients who were treated for first primary breast cancer and 14 patients who had previously received treatment for a prior cancer. A pCR was observed in 65 of the 107 patients (61 %). Platinum-based chemotherapy is effective in a high proportion of patients with BRCA1-associated breast cancer. | 10.1007/s10549-014-3100-x |
pubmed_621_16909 | Gut flora and bacterial translocation (BT) play important roles in the pathogenesis of chronic liver disease, including cirrhosis and its complications. Intestinal bacterial overgrowth and increased bacterial translocation of gut flora from the intestinal lumen predispose patients to bacterial infections, major complications and also play a role in the pathogenesis of chronic liver disorders. Levels of bacterial lipopolysaccharide, a component of gram-negative bacteria, are increased in the portal and/or systemic circulation in several types of chronic liver disease. Impaired gut epithelial integrity due to alterations in tight junction proteins may be the pathological mechanism underlying bacterial translocation. Preclinical and clinical studies over the last decade have suggested a role for BT in the pathogenesis of nonalcoholic steatohepatitis (NASH). Bacterial overgrowth, immune dysfunction, alteration of the luminal factors, and altered intestinal permeability are all involved in the pathogenesis of NASH and its complications. A better understanding of the cell-specific recognition and intracellular signaling events involved in sensing gut-derived microbes will help in the development of means to achieve an optimal balance in the gut-liver axis and ameliorate liver diseases. These may suggest new targets for potential therapeutic interventions for the treatment of NASH. Here, we review some of the mechanisms connecting BT and NASH and potential therapeutic developments. | 10.3748/wjg.v18.i21.2609 |
pubmed_1004_4481 | Antivenom antibodies were raised in 24-week-old white leghorn chickens against hemotoxic venoms of Russell's viper and Saw-scaled viper snakes. Booster injections of increasing concentrations of venom were given at 14days of time interval to raise the antivenom level in egg yolk. Antibodies were extracted from immunized chicken egg yolk by Polson et al. (Polson A., Von Wechmar M.B., Van Regenmortel M.H.V. Isolation of viral IgY antibodies from yolks of immunized hens. Immunological Communications 1980; 9:475-493.) and further purified by DEAE cellulose ion exchange column chromatography, which gave pure (180-200kDa) specific antibodies against venom. High titre of more than 1:10,000 antibodies were detected by ELISA at the 135th day of observation. The lethal toxicity and various pharmacological activities like hemorrhagic activity, phospholipase activity, edema and procoagulant activities of venom were carried out by both in vivo and in vitro methods. The effectiveness of antivenom in neutralizing these effects was carried out involving pre-incubation type experiments. The median effective dose (ED50) for Russell's viper venom was 0.96mg/2LD50/18g mice and for Saw-scaled viper venom it was 1.28mg/2LD50/18g mice. One millilitre of specific antivenom was effective in neutralizing 0.110mg of Russell's viper and 0.137mg of Saw-scaled viper venoms respectively (PD50). Antivenom was effective in neutralization assays in a dose dependent manner. The results indicate that antibodies raised in chicken could effectively neutralize the pharmacological effects induced by venoms and chickens therefore present an alternative and cheaper source of specific antibody generation. | 10.1016/j.intimp.2008.03.017 |
pubmed_957_21739 | BACKGROUND
Known as a disease associated with high mortality, disability and a significant financial burden, ischemic stroke ranks as one of the three diseases threatening human health. Recent advances in omics technology created opportunities to uncover the mechanism in ischemic stroke occurrence and treatment. In this study, we aimed to construct the competitive endogenous RNA (ceRNA) networks of ischemic stroke treated by oxymatrine intervention.
METHOD
The middle cerebral artery occlusion (MCAO) mouse model of ischemic stroke was constructed, and oxymatrine was administered. Then RNA-Sequencing was performed and integrated analysis of mRNAs, lncRNAs and circRNAs was conducted to reveal the pharmacology of oxymatrine. Functional enrichment analysis was performed to explore the underlying mechanism of differentially expressed (DE) mRNAs. The protein-protein interaction (PPI) network of neurogenesis-related genes and long noncoding RNAs (lncRNAs)/circular RNAs (circRNAs) based ceRNA networks were constructed.
RESULTS
First, this study revealed the DE-mRNAs, DE-lncRNAs and DE-circRNAs between Oxymatrine treated group and the MCAO group. Then, the common 1231 DE-mRNAs, 32 DE-lncRNAs and 31 DE-circRNAs with opposite trends were identified. The Kyoto Encyclopedia of Genes and Genomes to identify the functional enrichment of 1231 DE-mRNAs were enriched in neurogenesis-related biological processes. Based on neurogenesis-related DE-mRNAs, the PPI network was constructed, and hub genes were identified based on centrality. Finally, both the lncRNA-based and circRNAs-based ceRNA networks were constructed.
CONCLUSION
In summary, this study identified novel coding and noncoding ischemic stroke targets of oxymatrine-treated MCAO. Most importantly, we identified lncRNAs and circRNAs candidates as potential oxymatrine targets and constructed the neurogenesis-related ceRNA networks. | 10.1097/WNR.0000000000001827 |
pubmed_680_3154 | Protein secretion in cancer cells defines tumor survival and progression by orchestrating the microenvironment. Studies suggest the occurrence of active secretion of cytosolic proteins in liver cancer and their involvement in tumorigenesis. Here, we investigated the identification of extended-synaptotagmin 1 (E-Syt1), an endoplasmic reticulum (ER)-bound protein, as a key mediator for cytosolic protein secretion at the ER-plasma membrane (PM) contact sites. Cytosolic proteins interacted with E-Syt1 on the ER, and then localized spatially inside SEC22B+ vesicles of liver cancer cells. Consequently, SEC22B on the vesicle tethered to the PM via Q-SNAREs (SNAP23, SNX3, and SNX4) for their secretion. Furthermore, inhibiting the interaction of protein kinase Cδ (PKCδ), a liver cancer-specific secretory cytosolic protein, with E-Syt1 by a PKCδ antibody, decreased in both PKCδ secretion and tumorigenicity. Results reveal the role of ER-PM contact sites in cytosolic protein secretion and provide a basis for ER-targeting therapy for liver cancer. | 10.1073/pnas.2202730119 |
pubmed_405_14259 | After two decades of frustration, genetic studies of schizophrenia have entered an era of spectacular success. Advances in genotyping technologies and high throughput sequencing, increasing analytic rigour and collaborative efforts on a global scale have generated a profusion of new findings. The broad conclusions from these studies are threefold: (1) schizophrenia is a highly polygenic disorder with a complex array of contributing risk loci across the allelic frequency spectrum; (2) many psychiatric illnesses share risk genes and alleles, specifically, schizophrenia has substantial overlaps with bipolar disorder, intellectual disability, major depressive disorder and autism spectrum disorders; and (3) some convergent biological themes are emerging from studies of schizophrenia and related disorders. In this commentary, we focus on the very recent findings that have emerged in the past 12 months, and in particular, the areas of convergence that are beginning to emerge from multiple study designs. | 10.1038/mp.2014.148 |
pubmed_486_23850 | Millions of individuals in the United States will have their exomes and genomes sequenced over the next 5 years as the use of genomic sequencing technologies in clinical care grows and as initiatives in personalized medicine and precision health move forward. As a result, we will see a shift away from the patient population of early adopters who pursued direct-to-consumer (DTC) testing and paid thousands of dollars to get their genomes sequenced and toward a different and more diverse set of test takers. Early data suggest that these individuals will have different motivations for pursuing genomic sequencing and will be less knowledgeable about and less confident of the benefits of genetic testing. To serve this growing population, genetic counselors must understand our future patients as well as the changing landscape of genomic testing, DTC offerings, and population sequencing initiatives. | 10.1101/cshperspect.a036699 |
pubmed_336_16668 | AIM
The aim of this study was to assess the performance of FDG PET/ceCT simultaneously acquired, contemporary read and finally discussed by the radiologist and the nuclear medicine physician for staging and restaging lung cancer patients.
METHODS
We analysed 17 consecutive patients (7F; 10M; mean age 68). Six patients were in staging, 8 patients were in restaging (1 during therapy, 2 after therapy and 5 during the follow-up) and 2 patients needed to characterise a suspect pulmonary mass. All the patients underwent combined FDG PET/CT and ceCT acquired simultaneously on the same tomograph. The images were read and reported together by the nuclear medicine physician and the radiologist.
RESULTS
None of the patients had adverse reactions nor complained about the procedure. Thirteen FDG PET/ceCT turned out positive, while 4 were completely negative. Among positive patients, a significant SUV max was detected in all the cases (range 1.8-17.5). In the end, 9 patients had a true positive result, 4 true negative, 3 false positive and 1 false negative. Sensitivity, specificity and accuracy of the combined procedure were 90%, 57% and 76% respectively. In 7/17 patients FDG PET/CT and ceCT were completely concordant. FDG PET/CT provided a significant impact on the final interpretation in 7/17 patients while ceCT had a major impact in 3/17 patients.
DISCUSSION
This preliminary study shows that FDG PET/ceCT is a feasible technique for lung cancer patients, providing an optimal sensitivity (90%). From our results it is advisable not to include patients without an histological diagnosis of cancer due to possible false positivity of the two methods, significantly reducing specificity. However, a proper patient selection is not easy and the future of this combined test relies essentially on the capacity to early identify only the subjects who would really benefit from both the procedures. | pubmed_336_16668 |
pubmed_1093_880 | OBJECTIVE
Developmental venous anomalies (DVAs) are benign anatomic variations; therefore, they are usually discovered incidentally. The aim of this article was to describe radiological findings of DVAs.
METHODS
A retrospective search for DVAs of the brain was performed in 1899 patients who had undergone magnetic resonance imaging (MRI) with contrast enhancement between January 1, 2005 and April 25, 2011. We also reviewed the results of computed tomography (CT), magnetic resonance angiography (MRA), CT angiography, and transfemoral cerebral angiography (TFCA) studies performed in patients with DVAs.
RESULTS
Thirty-two DVAs were identified in 31 of the 1899 patients (1.63%). These 31 patients underwent five enhanced CTs, three MRAs, two CT angiographies, and two TFCAs. Thirty of the 32 DVAs were supratentorial (ST) and two were infratentorial (IT). All enhanced MRI studies exhibited excellent resolution of DVAs. All DVAs had only one draining vein. The venous drainage system was an IT vein in three DVAs and an ST vein in 29 DVAs. Two out of five enhanced CTs presented good visualization of the draining vein. None of the MRAs, including the source image, revealed the presence of DVAs. The two CT angiographies exhibited good resolution of DVAs. One of the two TFCAs yielded an excellent illustration of the DVA.
CONCLUSION
CT angiography and MRI with contrast enhancement yielded detailed findings of DVAs. In contrast, MRA did not identify the DVAs. Enhanced CT presented only the draining vein of DVAs. | 10.7461/jcen.2012.14.1.37 |
pubmed_397_10789 | Frogs have one of the most extreme metamorphoses among vertebrates. How did this metamorphosis evolve? By combining the methods previously proposed by Mabee and Humphries (1993) and Velhagen (1997), I develop a phylogenetic method suited for rigorous analysis of this question. In a preliminary analysis using 12 transformation sequence characters and 36 associated event sequence characters, all drawn from the osteology of the skull, the evolution of metamorphosis is traced on an assumed phylogeny. This phylogeny has lissamphibians (frogs, salamanders, and caecilians) monophyletic, with frogs the sister group of salamanders. Successive outgroups used are temnospondyls and discosauriscids, both of which are fossil groups for which ontogenetic data are available. In the reconstruction of character evolution, an unambiguous change (synapomorphy) along the branch leading to lissamphibians is a delay in the lengthening of the maxilla until metamorphosis, in accordance with my previous suggestion (Reiss, 1996). However, widening of the interpterygoid vacuity does not appear as a synapomophy of lissamphibians, due to variation in the character states in the outgroups. From a more theoretical perspective, the reconstructed evolution of amphibian metamorphosis involves examples of heterochrony, through the shift of ancestral premetamorphic events to the metamorphic period, caenogenesis, through the origin of new larval features, and terminal addition, through the origin of new adult features. Other changes don't readily fit these categories. This preliminary study provides evidence that metamorphic changes in frogs arose as further modifications of changes unique to lissamphibians, as well as a new method by which such questions can be examined. | 10.1078/0944-2006-00059 |
pubmed_41_21622 | Phenotypic variability in maturity-onset diabetes of the young (MODY) makes screening criteria for genomic analysis challenging. We describe the clinical spectrum in a large pedigree with HNF1A-MODY; as generations progressed, the course and outcome became poorer. Although uncommon, pancreatic autoantibodies and diabetes ketoacidosis should not exclude the diagnosis of MODY. | 10.1016/j.diabres.2017.10.024 |
pubmed_762_986 | Fibronectin is one of the cell adhesion proteins. Adhesion molecules play an important role in neural and synaptic genesis, and their dysfunction may result in neurodevelopmental abnormalities, which have been assumed to be a factor in the pathogenesis of schizophrenia. To examine the possible involvement of fibronectin in the etiology of schizophrenia, we analyzed six polymorphisms, located in introns 2, 21, 24, and 26, and exons 20 and 28, in the human fibronectin gene (FN1) of schizophrenic patients in the Japanese population (n = 104) and age-and gender-matched controls (n = 104). No significant positive association was observed between either of the polymorphisms and schizophrenia, nor was an association found between either of the polymorphisms and any subtypes of schizophrenia. These data did not provide evidence for a contribution of the FN1 gene to susceptibility to schizophrenia. | 10.1002/ajmg.b.10796 |
pubmed_97_12688 | Mice were immunized with either inactivated whole virus influenza A (H3N2) virus (WV) vaccine or with purified N2 neuraminidase (NA) vaccine then challenged with mouse-adapted homologous infective virus at intervals of 1-141 days later in order to ascertain the optimal vaccine-infection interval for induction of resistance to subsequent infection. Measured by serological or infection suppressing response, this interval was 15 days for both vaccines. Maximal reduction in pulmonary virus replication during initial (postvaccination) infection was achieved with WV vaccine, but in second infection by NA vaccine. This study provides further support for the concept of infection-permissive immunization with NA vaccines and suggests the promise of programmed antigenic stimulation by coupling of non-replicating and replicating antigens in the induction of solid immunity. | 10.1016/0264-410x(91)90059-f |
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