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pubmed_106_677 | Two strains of microorganisms that both use sugar as energy resource, but which may choose between two different pathways of ATP production, are studied from a game-theory point of view. We consider these pathways as distinct strategies to which we assign payoffs that are proportional to the expected steady-state number of individuals sustainable on the basis of these strategies. In a certain parameter range, we find that the payoffs fulfil the conditions for the prisoner's dilemma. Therefore, cooperative behaviour is unlikely to occur, unless additional factors intervene. In fact, the yeast Saccharomyces cerevisiae uses a competitive strategy by fermenting sugars even under aerobic conditions, thus wasting its own resource. The simple quantifiable structure of the model should enable access to an experimentally determined payoff matrix. | 10.1007/s00114-003-0434-3 |
pubmed_120_5521 | Ileal pouch-anal anastomosis (IPAA) is the preferred surgical therapy for chronic ulcerative colitis (CUC) and familial adenomatous polyposis (FAP). Previous studies have demonstrated morphologic changes in pouch mucosa such as villous atrophy and crypt hyperplasia. These changes have been labeled "colonic metaplasia." The aims of this study were to determine whether these changes represent "normal" long-term adaptation of the nondiseased pouch or instead are present only in the setting of inflammation. Twenty-four patients were identified, greater than 5 years status post-IPAA for CUC, who underwent pouchoscopy for surveillance and had no history of pouchitis. Thirty-one patients were identified greater than 5 years status post-IPAA for CUC, who had a history of pouchitis and had undergone pouchoscopy at least 5 years status post-IPAA. Eight patients status post-IPAA for FAP were also identified. Biopsy specimens were reevaluated by a single, blinded pathologist for degree of inflammation, the presence of villous atrophy and crypt hyperplasia, and evidence of dysplasia. Among the patients with CUC, the inflammation score was greater in the pouchitis group, 13.2 +/- 1.2, compared to the nonpouchitis group, 4.0 +/- 0.5 (P < 0.0001). Median colonic metaplasia score was greater in the pouchitis group (4 [range 2 to 6]) vs. 2 (9 [range 0 to 6]; P < 0.0001). The colonic metaplasia score correlated with the inflammation score (Spearman coefficient r = 0.83; P < 0.0001). In the eight patients with FAP, the inflammation score was 5.1 +/- 0.9 and the median colonic metaplasia score was 1 (range 0 to 4). There was no evidence of dysplasia in any of the biopsy specimens. Patients without a history of pouchitis or symptoms of pouchitis have only a minimal degree of villous atrophy and crypt hyperplasia. These morphologic changes in the ileal pouch are found primarily in the setting of inflammation, and likely represent a reparative response. | 10.1016/s1091-255x(02)00191-9 |
pubmed_714_7992 | Primary orbital intraosseous angiomas are rare. The authors report the case of a 55-year-old man who harbored a multifocal cavernous angioma in an unusual sphenoorbital location. The lesion was responsible for unilateral exophthalmos and blindness. Characteristic imaging findings, which included a honeycomb pattern on plain x-ray films and computerized tomography scans, a heterogeneous high signal intensity on T2-weighted magnetic resonance images, and slowly flowing venous lakes on power Doppler ultrasonograms and angiograms, are presented and discussed. | 10.3171/jns.1999.91.6.1034 |
pubmed_1104_10507 | We present the results of a 4-month field investigation of positional behavior, vertical ranging, and species differences in limb proportions and body mass in a mixed-species troop of Saguinus fuscicollis, Saguinus labiatus, and Callimico goeldii in northwestern Brazil. Despite certain similarities in overall positional repertoire, patterns of positional behavior varied significantly between species. Travel in Callimico occurred principally in the lowest levels of the canopy, and was characterized by an exaggerated form of hindlimb-dominated bounding (bounding-hop), and leaping to and from vertical trunks (55.1% of leaps). In contrast, saddle-back tamarins traveled in the lower and middle levels of the canopy, and engaged in a range of leaping behaviors, including stationary leaps (37.3%), acrobatic leaps (31.3%), and trunk-to-trunk leaps (20%). Red-bellied tamarins exploited the highest levels of the arboreal canopy. Travel in this species was dominated by quadrupedal bounding and acrobatic leaps (67% of leaps) that began and ended on thin, flexible supports. Species differences in positional behavior correlated with species differences in limb proportions and locomotor anatomy, and provide a framework for understanding niche partitioning in mixed-species troops of Saguinus and Callimico. | 10.1002/ajp.1009 |
pubmed_182_7600 | We present a rare case of rasburicase-induced methemoglobinemia and hemolytic anemia in the setting of presumed glucose-6-phosphate dehydrogenase (G6PD) deficiency. A 78-year-old male with a known history of chronic lymphocytic leukemia presented to the clinic with fever of unknown origin. Laboratory results were significant for hyperuricemia. He was empirically started on levofloxacin and rasburicase. He then presented to the emergency department with shortness of breath and syncope. Physical examination was remarkable for a fever of 102.8 °F, conjunctival pallor, and scleral icterus. An infiltrate was observed on his computed tomography (CT) angiogram of the chest. Arterial blood gas on 50% fraction of inspired oxygen was significant for an arterial oxygen level of 222 millimeters mercury and oxyhemoglobin of 85.9%. Co-oximetry was then obtained and methemoglobin level was 13.4%. Laboratory results were noteworthy for a drop-in hemoglobin, indirect hyperbilirubinemia, low haptoglobin and elevated lactate dehydrogenase; depicting hemolytic anemia. The patient received two units of packed red blood cells, intravenous broad-spectrum antibiotics and he clinically improved. | 10.7759/cureus.3084 |
pubmed_628_18972 | A high-dispersion spectrum of Comet C/1999S4 (LINEAR) was obtained in the optical region with the high-dispersion spectrograph on the Subaru telescope when the comet was 0.863 astronomical units from the Sun before its disintegration. We obtained high signal-to-noise ratio emission lines of the cometary NH2 bands from which an ortho-to-para ratio (OPR) of 3.33 +/- 0.07 was derived on the basis of a fluorescence excitation model. Assuming that cometary NH2 mainly originates from ammonia through photodissociation, the derived OPR of NH2 molecules should reflect that of ammonia, which provides information on the environment of molecular formation or condensation and of the thermal history of cometary ices. Assuming that the OPR of ammonia in comets was unchanged in the nucleus, the derived spin temperature of ammonia (28 +/- 2 kelvin) suggests that a formation region of the cometary ammonia ice was between the orbit of Saturn and that of Uranus in the solar nebula. | 10.1126/science.1064339 |
pubmed_695_4293 | PURPOSE
This retrospective study compared effectiveness between ≤4 cycles and ≥5 cycles of L-asparaginase/pegaspargase-based chemoradiation in newly diagnosed low-risk extranodal natural killer/T-cell lymphoma (ENKTL), nasal type classified according to the Prognostic Index of Natural Killer (PINK) lymphoma model.
PATIENTS AND METHODS
Patients were categorized into ≤4-cycle (2-4 chemotherapy cycles, n = 166) and ≥5-cycle groups (5-6 cycles, n = 86). Propensity score matching analysis was used to reduce potential confounding bias between the two groups. Treatment responses, adverse events, and survival outcomes between the two groups were analyzed.
RESULTS
No matter before or after matching (65 in the ≤4-cycle group, 65 in the ≥5-cycle group), response rates and survival outcomes were similar between the ≤4-cycle and ≥5-cycle groups. Incidences of grade 1-2 anemia and transaminase elevation were higher in the ≥5-cycle group. After matching, for stage IE disease, there were no differences in response rates and survival outcomes between the two groups. For stage IIE disease, the complete response rate was higher in the ≥5-cycle group (72.4% vs 92.6%, p = 0.049), and the 3-year overall survival (65.5% vs 85.2%, p = 0.024) and 3-year progression-free survival (58.6% vs 81.5%, p = 0.027) rates were significantly extended in the ≥5-cycle group.
CONCLUSION
When chemoradiotherapy strategies with L-asparaginase/pegaspargase-based regimens are applied to modern low-risk ENKTL patients classified according to the PINK model, it may be better to moderately extend chemotherapy courses in patients with stage IIE disease. | 10.2147/TCRM.S254246 |
pubmed_815_2652 | Worldwide, squamous cell cervical cancer and intraepithelial lesions (SIL) are a major source of morbidity and mortality. Compared to women in general, women with human immunodeficiency syndromes (HIV) are at higher risk of developing SIL. With the HIV epidemic escalating among women, prevalence, morbidity, and mortality related to SIL are likely to increase unless adequate prevention and detection programs are mounted. Consequently, this article provides background information for the design of such programs, focusing on selected biochemical risk factors and natural history of SIL in women infected with HIV (HIV+) and women in general (HIV-). Current screening policies are described, and implications for nursing research and policy are discussed. | pubmed_815_2652 |
pubmed_52_18541 | Wetlands are important sinks for nutrients and constructed wetlands are current practice for stormwater treatment. For nitrogen, the main removal process is denitrification (microbial reduction of nitrate to nitrogen gas). The bacteria responsible for this process are mostly found in the sediments and in epiphytic biofilms growing on wetland macrophytes. This paper reports on a project which aimed at measuring denitrification potential in sediments and epiphyton in urban wetlands. This study showed that wetland sediments could support high rates of denitrification. Interestingly, the most polluted of the wetlands studied had the highest denitrification potential. The management implication from this result is that indicators of pollution, such as hydrocarbon levels, will not necessarily reflect the ability of a wetland to denitrify. Two of the wetlands were studied in more detail. Here the denitrification potential of the epiphyton on dominant macrophytes and sediments were measured. The results indicated that the potential denitrification activity of the epiphyton was comparable to those measured in the sediments. Hence, biofilms could play a significant part in removing nitrogen loads. This work contributes to a better knowledge of the functioning of wetlands. This will lead to improved design and management of wetlands used for treating stormwater. | 10.2166/wst.2007.107 |
pubmed_206_16835 | The higher expression of methionine cycle genes in melanoma cells than in normal melanocytes may be related with increased protein synthesis and transmethylation reactions and the subsequent need for high levels of methionine. 3-O-(3,4,5-trimethoxybenzoyl)-(-)-epicatechin (TMECG), a trimethoxy derivative of epicatechin-3-gallate (ECG), effectively suppressed proliferation of melanoma cells in cultures by inducing apoptosis. TMECG modulates the expression of genes involved in methionine metabolism, cellular methylation and glutathione synthesis in melanoma cells. TMECG treatment of melanoma cells resulted in the downregulation of antiapoptotic Bcl-2, the upregulation of proapoptotic Bax and the activation of caspase-3; however, it did not induce the expression of the apoptosis protease-activating factor-1 (Apaf-1). Having elucidated the effects of TMECG on the melanoma methionine cycle, we designed therapeuthical strategies to increase its effectiveness. Combinations of TMECG with S-adenosylmethionine or compounds that modulate the intracellular concentration of adenosine strongly increase the antiproliferative effects of TMECG. The ability of TMECG to target multiple aspects related with melanoma survival, with a high degree of potency, points to its clinical value in melanoma therapy. | 10.1002/ijc.23813 |
pubmed_1059_6904 | Hexobarbital sleeping time was observed in isolated and nonisolated rats with lesioned locus coeruleus (LC). Isolated animals were divided into 2 groups: aggressive (killers) and indifferent (nonkillers). Each group included rats with no lesion, with sham lesion and with LC lesion. Hexobarbital sleeping time was prolonged in nonisolated male, but not female, rats with lesioned LC (7 and 14 days after the lesion). This effect was not observed in animals previously isolated for 3 weeks. These results suggest that the LC plays an important role in the mechanisms of barbiturate sleep, but this effect may be related to the emotionality of animals. | pubmed_1059_6904 |
pubmed_251_20389 | RNA substrates which form relatively short helices I and III with hammerhead ribozymes are generally cleaved more rapidly than substrates which create longer binding helices. We speculated that for optimum cleavage rates, one of the helices needed to be relatively weak. To identify this helix, a series of ribozymes and substrates of varying lengths were made such that in the complex, helices I and III consisted of 5 and 10 bp respectively or vice versa. In two independent systems, substrates in the complexes with the shorter helix I and longer helix III were cleaved one to two orders of magnitude more rapidly than those in the complexes with the longer helix I and shorter helix III. Similar results were obtained whether the numbers of base pairs in helices I and III were limited either by the length of the hybridizing arms of the ribozyme or the length of the substrate. The phenomenon was observed for both all-RNA and DNA armed ribozymes. Thus, a relatively short helix I is required for fast cleavage rates in pre-formed hammer-head ribozyme-substrate complexes. When helix III has 10 bp, the optimum length for helix I is approximately 5 bp. | 10.1093/nar/24.14.2679 |
pubmed_583_19552 | The dopamine transporter (DAT) is a membrane glycoprotein responsible for dopamine (DA) uptake, which has been involved in the degeneration of DA cells in Parkinson's disease (PD). Given that DAT activity depends on its glycosylation status and membrane expression, and that not all midbrain DA cells show the same susceptibility to degeneration in PD, we have investigated a possible relationship between DAT glycosylation and function and the differential vulnerability of DA cells. Glycosylated DAT expression, DA uptake, and DAT V(max) were significantly higher in terminals of nigrostriatal neurons than in those of mesolimbic neurons. No differences were found in non-glycosylated DAT expression and DAT K(m), and DA uptake differences disappeared after deglycosylation of nigrostriatal synaptosomes. The expression pattern of glycosylated DAT in the human midbrain and striatum showed a close anatomical relationship with DA degeneration in parkinsonian patients. This relationship was confirmed in rodent and monkey models of PD, and in HEK cells expressing the wild-type and a partially deglycosylated DAT form. These results strongly suggest that DAT glycosylation is involved in the differential vulnerability of midbrain DA cells in PD. | 10.1016/j.nbd.2009.09.002 |
pubmed_203_4719 | BACKGROUND
Treatment satisfaction of patients with primary immunodeficiency diseases receiving hospital-based intravenous (IVIG) or home-based subcutaneous (SCIG) immunoglobulin infusions requires investigation.
OBJECTIVE
Evaluation of the properties and suitability of the Life Quality Index (LQI), as an instrument to assess treatment satisfaction.
METHODS
Patients received weekly SCIG and completed the LQI, two global treatment satisfaction questions and the CHQ-PF50 (children) or the SF-36 (adults) at baseline and 10 months. The LQI was psychometrically evaluated.
RESULTS
The LQI comprised four scales: treatment interference (I), therapy related problems (II), therapy setting (III), treatment costs (IV). Convergent/discriminant validity for scales I, II, III was acceptable, for scale IV moderate. CHQ-PF50 scales behavior, bodily pain, global behavior, global health, mental health, parental impact-emotion significantly correlated with LQI scale II, the family activity scale with LQI scales I, III. SF-36 scale bodily pain significantly correlated with scale III. Internal consistency was good for scales I, II, III, but poor for scale IV. Score values significantly increased for scales I, III, IV in patients switching from IVIG to SCIG.
CONCLUSIONS
Three valid LQI scales were determined. Cost-related questions should be removed due to low reliability. Patients-perceived therapy effectiveness and patient-physician/nurse interaction should be included in the instrument. | 10.1007/s11136-005-1746-x |
pubmed_142_17507 | BACKGROUND
The Diagnostic Criteria for Psychosomatic Research (DCPR) are a set of 12 psychosomatic syndromes and are provided with a reliable diagnostic structured interview. The DCPR have been proposed 20 years ago as an integrative assessment strategy that supplements the traditional psychiatric nosography for identifying patients within a given illness population whose psychosocial factors have clinical significance. This paper reviews their clinical utility, conceived as the degree and the amount of influence that the instrument has on multiple decisions and outcomes in clinical practice.
METHODS
Published reports which involved the use of the DCPR were identified by searching electronic databases. Studies which best displayed the clinical utility of the DCPR system were then selected and reviewed.
RESULTS
The DCPR system showed its clinical utility regarding the following clinical issues: (1) subtyping medical patients, (2) identifying subthreshold or undetected syndromes, (3) evaluating the burden of somatic syndromes, and (4) predicting treatment outcomes and identifying risk factors.
CONCLUSIONS
The DCPR may help clinicians during the assessment process to recognize clinical conditions underlying symptom presentation, with important therapeutic and prognostic implications. | 10.1159/000430788 |
pubmed_1074_16739 | BACKGROUND
Self-injurious behavior (SIB) in older adults is defined as harm inflicted on oneself without conscious suicidal intent. SIB as a separate entity distinct from suicidal intent is poorly understood. However, it is of great concern to the patients' families and caregivers and it poses serious clinical challenges for clinicians.
METHODS
We searched the database of PubMed, Ovid Medline, and ScienceDirect for reports published between 1970 and 2009 using combination of the following keywords: "self-injurious behavior", "self-destructive behavior", "self-mutilating behavior", "older adults", "geriatric population", and "nursing homes". The term "self-harm behavior" which also appears in the literature is broader in scope than "self-injurious behavior". It encompasses high suicide intent and failed suicide attempts; therefore, we excluded this term in order to focus purely on "self-injurious behavior". Our search yielded 10 publications concerning SIB in older adults, four of which included studies investigating SIB in nursing homes.
RESULTS
Clinical studies of SIB in older adult nursing home residents are sparse. This limited literature suggests that SIB is a prevalent phenomenon and is reported to be as high as 14% in one study of nursing home subjects aged 65 and older. It is reported to be strongly associated with dementia and a risk of accidental death. It has been suggested that SIB among demented patients occurs in the context of poor impulse control and physical isolation.
CONCLUSION
SIB is likely a common phenomenon in older adult nursing home residents. There is little evidence-based treatment guidance for SIB in older population. | 10.1002/gps.2486 |
pubmed_928_5263 | An experimental study on rats was performed to observe pathogenetic factors causing cancerogenesis in operated stomach. In sets I and II without exogenous carcinogen exposition 450 rats were operated upon by a different methods. In groups I it was B II gastrectomy, B II with Braun's anastomosis, B II in Roux en Y modification, B I and B I with jejunal interposition. In group II non-resective methods were tested: gastroenterostomy, gastroenterostomy with Braun's anastomosis, gastroenterostomy in Roux en Y modification, and vagotomy with pyloroplasty. In the group III 147 rats with different gastric operations were submitted to oral nitrate and nitrate with ascorbic acid exposition. The results confirmed significant pathogenetic influence of enterogastric reflux on cancerogenesis in the operated stomach. Ascorbic acid added to the exogenous cancerogen leads to a suppression of development of gastric cancer in rats. | pubmed_928_5263 |
pubmed_315_4147 | FK506 inhibits the Ca2+/calmodulin-dependent protein phosphatase calcineurin, which plays a critical role in yeast subjected to salt stress. A chemical genetic screen for small molecules that suppress growth inhibition by high NaCl plus FK506 identified a structurally related class of suppressors of FK506 (SFKs) named SFKs 2-4. To identify possible protein targets for these small molecules, a genome-wide screen of approximately 4,700 haploid yeast deletion strains was undertaken for strains showing resistance to high NaCl plus FK506. This screen yielded a number of genes not previously implicated in salt stress, including ALD6, which encodes an NADP(+)-dependent aldehyde dehydrogenase, and UTR1, which encodes an NAD+ kinase. Transcriptional profiling of yeast treated with SFK2 indicated that the SFKs target the Ald6p pathway. In addition, screening of the deletion strains for hypersensitivity to SFK2 yielded ZWF1, encoding glucose-6-phosphate dehydrogenase, which has been shown to play an overlapping role with Ald6p in NADPH production. Furthermore, the SFKs inhibited the activity of Ald6p in vitro. Having established that the SFKs target Ald6p, they were used as tools to implicate systematically other gene products in the Ald6p pathway, including Utr1p, which may function by supplying Ald6p with its NADP+ cofactor. Furthermore, growth improvement by the SFKs on high NaCl plus FK506 was shown to require GPD1, which encodes an NADH-dependent glycerol-3-phosphate dehydrogenase that is important for the production of glycerol in response to osmotic stress. | 10.1073/pnas.0402317101 |
pubmed_733_16751 | OBJECTIVES
To examine the combined effect of social class and weight at birth on cognitive trajectories during school age and the associations between birth weight and educational outcomes through to 33 years.
DESIGN
Longitudinal, population based, birth cohort study.
PARTICIPANTS
10 845 males and females born during 3-9 March 1958 with information on birth weight, social class, and cognitive tests.
MAIN OUTCOME MEASURES
Reading, maths, draw a man, copying designs, verbal and non-verbal ability tests at ages 7, 11, and 16, highest qualifications achieved by 33, and trajectories of maths standardised scores at 7-16 years.
RESULTS
The outcome of all childhood cognitive tests and educational achievements improved significantly with increasing birth weight. Analysis of maths scores at 7 and of highest qualifications achieved by 33 showed that the relations were robust to adjustment for potential confounding factors. For each kilogram increase in birth weight, maths z score increased by 0.17 (adjusted estimate 0.15, 95% confidence interval 0.10 to 0.21) for males and 0.21 (0.20, 0.14 to 0.25) for females. Trajectories of maths z scores between 7 and 16 years diverged for different social class groups: participants from classes I and II increased their relative position on the score with increasing age, whereas classes IV and V showed a relative decline with increasing age. Birth weight explained much less of the variation in cognition than did social class (range 0.5-1.5% v 2.9-12.5%).
CONCLUSIONS
The postnatal environment has an overwhelming influence on cognitive function through to early adulthood, but these strong effects do not explain the weaker but independent association with birth weight. | 10.1136/bmj.325.7359.305 |
pubmed_275_23669 | Our recent studies on breast carcinoma cell lines with differing tumorigenicity/invasiveness (MCF-7<MDA-MB-468<MDAMB-231<MDA-MB-435) had shown significantly decreasing expression levels of MMPs-1,-2,-3,-8,-9,-10,-11 and -13 with increasing cell density while the levels of TIMP-1 and -2 increased. This correlated well with a lower invasiveness of confluent cells. In the present study, we extend our in vitro studies on three-dimensional cultures of breast cancer cell lines MCF-7 and MDAMB-435 and the transcriptional control of MMP and TIMP-expression in two-dimensional cultures of MDA-MB-231 and -435 cells. The tumor spheroid model showed that MMP expression and proteolytic activity were considerably higher in loosely structured tumor groups as compared to densely growing "compact" cell complexes. These data suggested that cell density regulates MMP and TIMP transcription and therefore, we tested whether AP-1, NF kappa B and CRE are involved in this process. Gene silencing of c-jun in sparse cultures had an inhibitory effect on MMP-3, -9 and -13 expression, on proteolytic activity as well as on the invasive potential of the cells, thus confirming a role for AP-1.TIMP-1, and -2 expression was up-regulated as compared to control cells. Consistent with this, overexpression of c-jun and c-fos in confluent breast cancer cell lines leads to up-regulation of MMP expression, proteolytic activity and invasion as well as down-regulation of TIMP-1. In summary, we provide evidence that cell density influences the invasive potential of tumor cells via regulation of MMPs and TIMPs by AP-1, NF kappa B and CRE transcription factors. Overexpression of MMPs in sparse cultures could help explain early dissemination of potentially metastatic cells. | 10.1160/TH04-09-0601 |
pubmed_430_1818 | Tyrosine hydroxylase (TH) activity and the concentrations of norepinephrine (NE), serotonin (5-HT), and cyclic adenosine 3',5'-monophosphate (c-AMP) were measured in the heart, adrenals, and brain stem of paraplegic rats. Following spinal cord transection NE concentration in the heart dropped to 30% within 24 hours and that of 5-HT decreased to 60% of control. Tyrosine hydroxylase activity in the adrenals reached a peak at five days and was still twice that of sham-operated controls thirty days later. Five days following transection the TH activity and c-AMP levels in the brain stem were elevated while NE concentration remained low. At seven days, however, NE and 5-HT levels were higher than in controls while TH activity and c-AMP concentration dropped to control levels. The increase in TH activity in the brain stem may be due to curtailed end-product feedback inhibition and to reduced receptor activation. The sustained induction of the adrenal TH is probably a consequence of a continual stimulation of splanchnic nerves. | 10.1007/BF00966678 |
pubmed_655_18160 | A retrospective analysis of 113 consecutive cases of benign esophageal stricture, all secondary to gastroesophageal reflux, 100 treated conservatively, 13 treated surgically, has been carried out in conjunction with a postal questionnaire of patients. Patients were requested to grade both their swallowing ability and the acceptability of their treatment. Of those responding to questionnaire, 88% of patients treated conservatively found their treatment acceptable or better, and 72% were left with either no or minimal restriction of diet. There was no correlation between either the total number or frequency of dilatations and the result achieved. Similarly, patient satisfaction appears largely independent of these variables. Doctors should be wary of taking recurrence of a stricture after initial dilatation as indicating a poor eventual outcome or a dissatisfied patient. There was no difference in terms of either the result or patient satisfaction between conservatively treated and surgically treated patients. | 10.1093/dote/11.2.109 |
pubmed_1020_3527 | BACKGROUND
COVID-19 disease first appeared in 2019 and quickly spread worldwide, causing a global pandemic. The oral cavity represents a target of SARS-CoV-2, and oral lesions are observed in both non-hospitalized and hospitalized patients. This systematic review aims to investigate the frequency of oral manifestations in COVID-19 hospitalized patients.
METHODS
An electronic search was conducted in PubMed, Scopus, and Web of Science databases, including articles published up to September 2021. The review protocol was based on PRISMA-P. The risk of bias of the studies was assessed using the Joana Briggs Institute. The certainty of evidence was assessed using the GRADE instrument.
RESULTS
Fifty-nine articles were included: 19 case reports, 17 case series, 2 case-control studies, 13 cross-sectional studies, 4 observational studies, and 4 retrospective studies. Oral ulcers, cheilitis, and tongue lesions were more common in patients before hospitalization, while perioral pressure ulcers, macroglossia, blisters, and oral candidiasis were more recurrent in patients during hospitalization. The first could be related directly to COVID-19, while the latter could be caused by medical devices, treatments, prone position, and immunological impairment.
CONCLUSIONS
An accurate oral examination during the hospital admission of all confirmed COVID-19 cases is encouraged to recognize oral early manifestations and to apply appropriate treatments. | 10.3390/ijerph182312511 |
pubmed_266_12399 | Synthetic dendrimer peptides are a promising strategy to develop new FMD vaccines. A dendrimer peptide, termed B2T-3A, which harbors two copies of the major FMDV antigenic B-cell site [VP1 (140-158)], covalently linked to a heterotypic T-cell from the non-structural protein 3A [3A (21-35)], has been shown to protect pigs against viral challenge. Interestingly, the modular design of this dendrimer peptide allows modifications aimed at improving its immunogenicity, such as the replacement of the T-cell epitope moiety. Here, we report that a dendrimer peptide, B2T-3D, harboring a T-cell epitope from FMDV 3D protein [3D (56-70)], when inoculated in pigs, elicited consistent levels of neutralizing antibodies and high frequencies of IFN-γ-producing cells upon in vitro recall with the homologous dendrimers, both responses being similar to those evoked by B2T-3A. Lymphocytes from B2T-3A-immunized pigs were in vitro-stimulated by T-3A peptide and to a lesser extent by B-peptide, while those from B2T-3D- immunized animals preferentially recognized the T-3D peptide, suggesting that this epitope is a potent inducer of IFN-γ producing-cells. These results extend the repertoire of T-cell epitopes efficiently recognized by swine lymphocytes and open the possibility of using T-3D to enhance the immunogenicity and the protection conferred by B2T-dendrimers. | 10.3389/fvets.2020.00498 |
pubmed_238_21229 | INTRODUCTION
Clinical implications of readmission following initial hospitalization for acute ischemic stroke (AIS) are not known. We examined predictors of readmissions and impact of readmissions on subsequent mortality after first-ever AIS.
MATERIALS AND METHODS
Adults aged ≥18 years who survived to discharge after hospitalization for first-ever AIS from 2003 to 2019 were included in the study. For each patient, the overall burden of hospitalizations was measured as total number of hospitalizations and aggregate days spent hospitalized during follow-up. We used Poisson regression to estimate incident rate ratios (IRR) for predictors of re-hospitalization and time-dependent Cox regression to estimate hazard ratios (HR) for mortality.
RESULTS
Of 908 AIS survivors, 537 died, 669 had 2,645 readmissions over 4,535 person-years follow-up. Adjusted independent predictors of cumulative readmission inlcuded being white (IRR 1.21, 95% CI 1.03-1.42), dependency on discharge (IRR 1.27, 95% CI 1.17-1.38), cardio-embolism (IRR 1.35, 95% CI 1.18-1.45), smoking (IRR 1.21, 95% CI 1.08-1.35), anemia (IRR 1.40, 95% CI 1.24-1.57), arthritis (IRR 1.20, 95% CI 1.10-1.31), coronary artery disease (IRR 1.34, 95% CI 1.23-1.47), cancer (IRR 1.96, 95% CI 1.64-2.30), chronic kidney disease (IRR 1.36, 95% CI 1.21-1.57), COPD (IRR 1.18, 95% CI 1.04-1.34), depression (IRR 1.50, 95% CI 1.37-1.66), diabetes mellitus (IRR 1.48, 95% CI 1.36-1.48), and heart failure (IRR 1.17, 95% CI 1.03-1.34). Conversely, hyperlipidemia was associated with a lower risk of readmission (IRR 0.79, 95% CI 0.71-0.88). Mortality was significantly increased with each hospitalization and cumulative days spent in hospital.
CONCLUSIONS
Among survivors of AIS hospitalization, certain sociodemographic indicators, stroke-specific features, and several key comorbid conditions were associated with increased risk of readmissions, which in turn correlated with increased mortality. Therefore, lifestyle modification and optimal treatment of comorbidities are likely to improve the outcome after AIS. | 10.1080/21548331.2022.2128575 |
pubmed_250_12907 | Amyloid-beta (Abeta) is the core component of senile plaques, which are the pathological markers for Alzheimer's disease and cerebral amyloid angiopathy. DNA methylation/demethylation plays a crucial role in gene regulation and could also be responsible for presentation of senescence. Oxidative stress, which may be induced by Abeta, is thought to be an important contributor of DNA hyper-methylation; however, contradicting this is the fact that global DNA hypo-methylation has been found in aging brains. It therefore remains largely unknown as to whether Abeta does in fact cause DNA methylation/demethylation. Neprilysin (NEP) is one of the enzymes responsible for Abeta degradation, with its expression decreasing in both Alzheimer and aging brains. Using high-performance liquid chromatography (HPLC), we explore whether Abeta is responsible for alteration of the global DNA methylation status on a murine cerebral endothelial cells model, and also use methylation-specific PCR (MSPCR) to examine whether DNA methylation status is altered on the NEP promoter region. We find that Abeta reduces global DNA methylation whilst increasing NEP DNA methylation and further suppressing the NEP expression in mRNA and protein levels. Our results support that Abeta induces epigenetic effects, implying that DNA methylation may be part of a vicious cycle involving the reduction in NEP expression along with a resultant increase in Abeta accumulation, and that Abeta may induce global DNA hypo-methylation. | 10.1016/j.bbrc.2008.10.173 |
pubmed_1067_3397 | We and others have shown that the fetal pulmonary arterial smooth muscle potential for contraction and relaxation is significantly reduced compared with the adult. Whether these developmental changes relate to age differences in the expression and/or activity of key enzymes regulating the smooth muscle mechanical properties has not been previously evaluated. Therefore, we studied the catalytic activities and expression of myosin light chain kinase (MLCK) and myosin light chain phosphatase (MLCP) catalytic (PP1cdelta) and regulatory (MYPT) subunits in late fetal, early newborn, and adult rat intrapulmonary arterial tissues. In keeping with the greater force development and relaxation of adult pulmonary artery, Western blot analysis showed that the MLCK, MYPT, and PP1cdelta contents increased significantly with age and were highest in the adult rat. In contrast, their specific activities (activity/enzyme content) were significantly higher in the fetal compared with the adult tissue. The fetal and newborn pulmonary arterial muscle relaxant response to the Rho-kinase inhibitor Y-27632 was greater than the adult tissue. In addition to the 130-kDa isoform of MLCK, we documented the presence of minor higher-molecular-weight embryonic isoforms in the fetus and newborn. During fetal life, the lung pulmonary arterial MLCK- and MLCP-specific activities are highest and appear to be related to Rho-kinase activation during lung morphogenesis. | 10.1152/ajplung.00145.2005 |
pubmed_244_25053 | Hypoglycaemia in children is a major risk factor for adverse neurodevelopment with rates as high as 50% in hyperinsulinaemic hypoglycaemia (HH). A key part of management relies upon timely identification and treatment of hypoglycaemia. The current standard of care for glucose monitoring is by infrequent fingerprick plasma glucose testing but this carries a high risk of missed hypoglycaemia identification. High-frequency Continuous Glucose Monitoring (CGM) offers an attractive alternative for glucose trend monitoring and glycaemic phenotyping but its utility remains largely unestablished in disorders of hypoglycaemia. Attempts to determine accuracy through correlation with plasma glucose measurements using conventional methods such as Mean Absolute Relative Difference (MARD) overestimate accuracy at hypoglycaemia. The inaccuracy of CGM in true hypoglycaemia is amplified by calibration algorithms that prioritize hyperglycaemia over hypoglycaemia with minimal objective evidence of efficacy in HH. Conversely, alternative algorithm design has significant potential for predicting hypoglycaemia to prevent neuroglycopaenia and consequent brain dysfunction in childhood disorders. Delays in the detection of hypoglycaemia, alarm fatigue, device calibration and current high cost are all barriers to the wider adoption of CGM in disorders of hypoglycaemia. However, machine learning, artificial intelligence and other computer-generated algorithms now offer significant potential for further improvement in CGM device technology and widespread application in childhood hypoglycaemia. | 10.1111/pedi.13029 |
pubmed_335_6155 | PURPOSE
To study the dynamics and clinical determinants of chronic retinal nerve fiber layer thickness (RNFL) loss after methanol-induced optic neuropathy.
DESIGN
Prospective cohort study.
METHODS
All patients underwent complete ophthalmic evaluation including spectral-domain optical coherence tomography 3 times during 4 years of observation: 4.9 (±0.6), 25.0 (±0.6), and 49.9 (±0.5) months after discharge.
PARTICIPANTS
Eighty-four eyes of 42 survivors of methanol poisoning, mean age (standard deviation) of 45.7 (±4.4) years; and 82 eyes of 41 controls, mean age 44.0 (±4.2) years.
MAIN OUTCOME MEASURES
Global and temporal RNFL loss.
RESULTS
Abnormal RNFL thickness was registered in 13 of 42 (31%) survivors of methanol poisoning and chronic axonal loss in 10 of 42 (24%) patients. Significant decrease of global/temporal RNFL thickness during the observation period was found in the study population compared to the controls (P < .001). The risk estimate of chronic global RNFL loss for arterial blood pH < 7.3 at admission was 11.65 (95% confidence interval 1.91-71.12) after adjusting for age and sex. The patients with chronic axonal degeneration demonstrated progressive visual loss in 7 of 10 cases. The patients with abnormal RNFL thickness had magnetic resonance signs of brain damage in 10 of 13 vs 8 of 29 cases with normal RNFL thickness (P = .003). Signs of brain hemorrhages were present in 7 of 13 patients with abnormal RNFL thickness vs 5 of 29 cases with normal RNFL thickness (P = .015).
CONCLUSIONS
Methanol-induced optic neuropathy may lead to chronic retinal axonal loss during the following years. Arterial blood pH on admission is the strongest predictor of chronic RNFL thickness decrease. Chronic retinal neurodegeneration is associated with the progressive loss of visual functions and necrotic brain lesions. | 10.1016/j.ajo.2018.04.015 |
pubmed_909_5704 | Intravesical instillation of chemotherapeutic agents is a well-established treatment strategy to decrease recurrence following transurethral resection in non-muscle invasive bladder cancer. Gemcitabine is a recently developed treatment option. However, the curative effects of gemcitabine are far from satisfactory due to de novo or acquired drug resistance. In a previous study, we reported that intravesical administration of the c-Myc inhibitor KSI-3716 suppresses tumor growth in an orthotopic bladder cancer model. Here, we explored whether KSI-3716 inhibits gemcitabine-resistant bladder cancer cell proliferation. As expected from the in vitro cytotoxicity of gemcitabine in several bladder cancer cell lines, gemcitabine effectively suppressed the growth of KU19-19 xenografts in nude mice, although all mice relapsed later. Long-term in vitro exposure to gemcitabine induced gemcitabine-specific resistance. Gemcitabine-resistant cells, termed KU19-19/GEM, formed xenograft tumors even in the presence of 2 mg/kg gemcitabine. Interestingly, KU19-19/GEM cells up-regulated c-Myc expression in the presence of the gemcitabine and resisted to the gemcitabine, however was suppressed by the KSI-3716. The sequential addition of gemcitabine and KSI-3716 inhibited gemcitabine-resistant cell proliferation to a great extent than each drug alone. These results suggest that sequential treatment with gemcitabine and KSI-3716 may be beneficial to bladder cancer patients. | 10.18632/oncotarget.1545 |
pubmed_477_7636 | Of 65 adult class III patients with retropositioned maxillae subjected to Le Fort I Osteotomy, 16 were selected at random for a clinical and cephalometric examination of postoperative stability. Lateral head plates prior to treatment, 6 weeks post-treatment and 1 year post-treatment were compared. In 9 out of the 16 cases 5 year post-treatment head plates were available. Statistical evaluation of the longitudinal differences revealed the repositioned maxilla to remain stable. The upper lip, however, lost 44% of its postoperative advanced position within the 1st year subsequent to the operation. In the period between 1 year and 5 years postoperatively no further cephalometric changes of any significance were recorded. | 10.1016/s0301-0503(82)80017-9 |
pubmed_707_10985 | Pharmaceutical companies regularly fund patient organizations. It is important for patient organizations' credibility that there be transparency regarding this financial support. In Europe, the pharmaceutical industry promises to deliver transparency through self-regulation, as opposed to legally binding provisions, but self-regulation's effectiveness is contested. We compared the industry's transparency of funding in four Nordic countries that, given their general reputation for high transparency, offered a critical test of self-regulation's ability to deliver on its transparency promise. For 2017-2019, we compared: national rules regarding funding disclosure; disclosure practices as evidenced by the availability, accessibility, and format of company transparency reports; and disclosure data, including payment descriptions and sums. Transparency problems differed in kind and magnitude between countries. In Norway and Finland, unlike in Sweden and Denmark, data on funding were difficult to access and analyze and sometimes seemed incomplete or missing. We explain that a key factor allowing for country differences is the freedom given to a country's pharmaceutical industry trade associations to form self-regulatory rules, provided they do not fall below the weak, European-level minimum requirements. Transparency could be improved by aligning rules and practices with the FAIR data principles: that is, corporate disclosures should be findable, accessible, interoperable, and reusable. | 10.1177/00207314221083871 |
pubmed_668_1027 | 1. Two populations of morphologically intact mitochondria were isolated from embryonic, neonatal and adult chick liver by isopycnic centrifugation. 2. The protein/phospholipid ratio of the total mitochondrial fraction, the low-density mitochondria (B2, d1.176) and the high-density mitochondria (B3, d1.206) did not differ significantly. 3. During development there is a marked increase in the B2 fraction in relation to the B3 fraction. 4. Cytochrome oxidase and malate dehydrogenase activities as well as respiratory control increased during the embryonic development of the chick, though their rates of increase were not correlated. 5. In the three different embryonic stages that were investigated, as well as in the neonatal and adult chick, the protein/lipid as well as the protein/phospholipid ratio stayed constant and showed no progressive increase, as had been previously reported. 6. It was shown that forces greater than 18400g(av.) for 2h have to be used before chick liver mitochondria reach isopycnic equilibrium. 7. As for rat liver mitochondria, the constant protein/phospholipid ratio of the B2 and B3 fractions and their apparent morphological intactness leads one to conclude that the matrix space of B2 mitochondria is inaccessible to sucrose, whereas B3 mitochondria possess an inner membrane that is permeable to sucrose. | 10.1042/bj1230347 |
pubmed_526_5318 | The most common malignancy of biliary tract is gallbladder cancer (GBC) which is the third most common cancer in gastrointestinal tract. It is a lethal disease for most patients in spite of growing awareness and improved diagnostic techniques. GBC has a very poor prognosis and the 5 year survival rate is < 10%. Although etiology of the carcinoma of the gallbladder is still obscure, various factors have been implicated, cholelithiasis being the most frequent. The incidence of GBC worldwide is based on the gender, geography and ethnicity which suggest that both genetic and environmental factors can cause GBC. The major route of spread of gallbladder cancer (GC) is loco-regional rather than distant. It spreads by lymphatic, vascular, neural, intraperitoneal, and intraductal routes. Sonography is usually the most common imaging test to evaluate symptoms of biliary tract disease including suspected GC. With recent advances in imaging modalities like multi-detector computed tomography (CT) scanners, magnetic resonance imaging-positron emission tomography/CT diagnosis of gallbladder cancer has improved. Studies have also targeted molecular and genetic pathways. Treatment options have included extended and radical surgeries and adjuvant chemotherapy. This review article deals in detail with important aspects of carcinoma gallbladder and its manifestations and challenges. Role of various imaging modalities in characterization and accurate staging has been discussed. The loco-regional spread of this aggressive malignancy is dealt explicitly. | 10.12998/wjcc.v3.i3.231 |
pubmed_758_4289 | Bone mass has been proposed as a marker of cumulative exposure to oestrogen in women. We have studied the association between bone mass and breast cancer in postmenopausal women. In 126 cases of breast cancers and 126 controls, the bone mineral density (BMD) of the lumbar spine (L2-L4), femoral neck, trochanter and Ward's triangle was measured by dual-energy X-ray absorptiometry. All cases of cancer were confirmed by pathological reports. A questionnaire including information on reproductive history and other variables was collected. BMD was significantly higher among breast cancer patients than controls at all sites, except at the femoral neck where BMD was increased in the cancer group, but not significantly. After adjustment for potential confounding factors, the estimated relative risk of breast cancer in the highest quartile of BMD compared to the lowest quartile ranged from 2.5 to 4.8 for various sites of measurement. These results confirm that bone-mass density is a strong predictor for breast cancer in postmenopausal women. Women in the lowest quartile of bone mass appear to be protected against breast cancer. The mechanisms underlying this relation may be explained by cumulative exposure to oestrogen. | 10.1054/brst.2000.0247 |
pubmed_1033_1749 | BACKGROUND
This study sought to determine the impact of methicillin resistance on clinical features and outcomes in patients with Staphylococcus aureus (SA) infective endocarditis (IE).
METHODS
Retrospective chart review. Univariate and forward stepwise logistic regressions were conducted to determine which factors significantly affected death and systemic embolism.
RESULTS
From October 1995 to April 2002, 57 patients with a definite diagnosis of IE caused by SA were included: 28 cases of methicillin-sensitive SA infection and 29 methicillin-resistant SA (MRSA) infection. Patients with MRSA infection are more likely to have old age, underlying diseases, history of hospitalization within the last 6 months, nosocomial infection, and antibiotic use within the last 3 months. Patients with MRSA infection had clinical presentation of less systemic embolism and more sepsis and had a higher 3-month mortality rate. Methicillin resistance is an independent positive predictor of death and a negative predictor of systemic embolism.
CONCLUSIONS
MRSA became a dominant cause of SA IE. Although it caused a lower incidence of systemic embolism, MRSA infection had a higher mortality rate because of sepsis. | 10.1097/00000441-200409000-00003 |
pubmed_567_21657 | The burden of HIV in stable relationships places emotional, economic and physical stresses on families. We compared the influence of HIV notification on marital partnerships in northern Thailand among a cohort of HIV discordant couples, and identified factors associated with marital disruption. Data were collected using in-depth interviews with both members of six separated or divorced couples and 13 couples whose relationship remained intact. Five factors influenced marital stability following HIV notification: longer duration of relationship; economic constraints, extended family members' opinions, especially parents; the existence of children from the marriage; and fear of stigmatization by community members. Social influences, both overt and perceived, are important in shaping marital behaviour and decision-making in HIV epidemic areas. HIV counselling needs to be extended beyond the individual seeking testing to include stable partners (and perhaps further, to include the extended family), although it is recognized that this is not the norm for most HIV testing centres. | 10.1080/09540129947677 |
pubmed_158_11261 | There are three ethical ideas that undergird a Jewish approach to allocating scarce health care resources: the unique and absolute importance of every single human being, justice, and love. These three ideas are examined in light of the legal discussions that provide the context for health care decision making. Two classical sources are used, one that adjudicates the apportionment of a single flask of water between two men in the desert, and the other that creates an order of precedence when there are certain threatening situations. In the development of the legal tradition, several issues determine who receives care: ownership of resources, equitable distribution of resources, and effectiveness of treatment options. The obligation to provide access to medical care is reinforced by the values of tzedakah (justice) and love. | pubmed_158_11261 |
pubmed_862_11660 | The purpose of this study was to investigate the formation of drug nanoparticles from binary and ternary mixtures, consisting of dihydroartemisinin (DHA), a poorly water-soluble antimalarial drug, with water-soluble polymer and/or surfactant. Binary mixtures of drug/polyvinyl pyrrolidone K30 (PVP K30), binary mixtures of drug/sodium deoxycholate (NaDC), and ternary mixtures of drug/PVP K30/NaDC were prepared at different weight ratios and then ground by vibrating rod mill to obtain ground mixtures. Nanosuspension was successfully formed after dispersing ternary ground mixtures or DHA/NaDC ground mixtures in water. The ternary ground mixtures did not give superior nanosuspension in terms of particle size reduction and recovery of drug nanoparticles, but they provided more physically stable nanosuspensions than DHA/NaDC ground mixtures. The size of drug nanoparticles was decreased with increasing grinding time and lowering amount of PVP K30 and NaDC. About 95% of drug nanoparticles were found in the nanosuspension from ternary ground mixtures. Zeta potential measurement suggested that stable nanosuspension was attributable to adsorption of NaDC and PVP K30 onto surface of drug particles. Atomic force microscopy and transmission electron microscopy with selected area diffraction indicated that DHA in nanosuspension was existed as nanocrystals. The obtained nanosuspensions had higher in vitro antimalarial acitivity against Plasmodium falciparum than microsuspensions. The results suggest that co-grinding of DHA with PVP K30 and NaDC seems to be a promising method to prepare DHA nanosuspension. | 10.1080/03639040701662388 |
pubmed_694_1437 | We have identified a region of chromosome 1p31.1 that shows high frequency loss of heterozygosity (LOH) in human breast cancer. This region forms part of a 7 Mb YAC/BAC contig. In order to identify candidate sequences, mutation of which might contribute to the development of disease, we have carried out mapping studies of ESTs localized to 1p31.1. This analysis, coupled with library screening and a modified 5' RACE-PCR strategy, resulted in the identification and characterization of a novel gene (LPHH1) which is located adjacent to the smallest region of overlapping loss (SRO) seen in tumours. The 4209 bp open reading frame of the 7 kb LPHH1 transcript encodes a peptide which shows approximately 65% identity to rat latrophilin, a G-coupled, seven span transmembrane protein, which binds alpha-latrotoxin. In the human sequence, whilst conservation of the transmembrane domain is high, the intra- and extracellular domains show two regions of variable structure, which are presumably generated by alternative splicing. Surprisingly, while expression of the rat gene is tightly restricted to neurological and perhaps some endocrine cells, the human sequence appears to be expressed very widely in all normal tissues tested. Northern and RT-PCR analysis of a panel of tumour cell lines showed that LPHH1 expression was variable, apparently elevated in some lines and absent or markedly reduced in others. Furthermore, characterization of the range of transcripts encoded in a breast tumour cell line, compared to normal breast, suggested that gene product variability was higher in the tumour. | 10.1038/sj.onc.1202487 |
pubmed_132_23807 | To investigate the chemical constituents of Saussurea deltoidea, 10 compounds were isolated from the title plant by various chromatography methods such as silica gel, RP-18 silica gel, Sephadex LH-20 column chromatography, HPLC, et al. Their structures were elucidated by spectral analysis. Five isoprenoids and Five phenylpropanoids were isolated and elucidated as (3R, 6R, 7E) -3-hydroxy-4, 7-megastigmadien-9-one (1), (3S, 5R, 6S, 7E) -5, 6-epoxy-3-hydroxy-7-megastigmen-9-one (2), 3-hydroxy-beta-damascone (3), S-(+) -dehydrovomifoliol (4), megastigman-5-ene-3beta, 9R-diol (5), coniferaldehyde (6), beta-hydroxypropiovanillone (7), 3-hydroxy-1-(4-hydroxy-3, 5-dimethoxyphenyl) -1-propanone (8), dihydrosyringenin (9), 4-[(1S) -3-hydroxy-1-methoxypropyl]-2, 6-dimenthoxyphenol (10). All the compounds were isolated from S. deltoidea for the first time. | pubmed_132_23807 |
pubmed_743_23424 | Tilletia laevis Kühn (syn. Tilletia foetida (Wallr.) Liro.) causes wheat common bunt, which is one of the most devastating plant diseases in the world. Common bunt can result in a reduction of 80% or even a total loss of wheat production. In this study, the characteristics of T. laevis infection in compatible wheat plants were defined based on the combination of scanning electron microscopy, transmission electron microscopy and laser scanning confocal microscopy. We found T. laevis could lead to the abnormal growth of wheat tissues and cells, such as leakage of chloroplasts, deformities, disordered arrangements of mesophyll cells and also thickening of the cell wall of mesophyll cells in leaf tissue. What's more, T. laevis teliospores were found in the roots, stems, flag leaves, and glumes of infected wheat plants instead of just in the ovaries, as previously reported. The abnormal characteristics caused by T. laevis may be used for early detection of this pathogen instead of molecular markers in addition to providing theoretical insights into T. laevis and wheat interactions for breeding of common bunt resistance. | 10.5423/PPJ.OA.05.2021.0082 |
pubmed_900_14337 | OBJECTIVE
Medical education programs across the country are now required to conduct meaningful assessments of trainees' competencies, although uniform standards for conducting these evaluations have yet to be established. In 1999, the Indiana University School of Medicine introduced a comprehensive competency-based undergraduate curriculum. The overall goal of the curriculum is to make medical students' day-to-day experiences of training a source of learning about professionalism, communication, and aspects of medicine beyond factual knowledge. We sought to examine free-text comments by parents of pediatric inpatients as substrate for competency evaluation and feedback for third-year students on their pediatrics rotation.
METHODS
The study was conducted from June 2001 to February 2004. Parents of hospitalized children completed a short medical student evaluation form that included 2 questions inviting free-text response. We used narrative analysis, a qualitative research technique, to describe both the content and meaning of the parents' responses.
RESULTS
We collected 573 evaluations with narrative comments about 412 students. The most common aspect of medical student performance commented on by parents related to communication (53.8%). The next most common narrative comment was some form of affirmation of the student as a health care professional (26.0%). Other themes included establishing context for the comment, perceptions of the health care system, criticizing medical student performance, perceptions of the role of medical students, physical approach to the patient, expression of humility by the student, holistic approach to the patient, physical appearance of the student, superlative description of student, and advocating for the patient. Multiple themes were identified in 232 narrative comments (40.4%). Examples of each theme are provided.
CONCLUSIONS
Family members of pediatric inpatients are a valuable source of information about medical student performance in at least 2 of the Accreditation Council for Graduate Medical Education competency areas (Communication and Professionalism). Themes identified in this study could be used to inform the design of a comprehensive 360-degree student evaluation strategy. | 10.1016/j.ambp.2007.03.001 |
pubmed_983_10157 | OBJECTIVE
Total joint replacement has been proposed as an endpoint in disease modifying osteoarthritis drug (DMOAD) randomized clinical trials (RCTs); however, disparities have generated concerns regarding this outcome. A combined Osteoarthritis Research Society International (OARSI)/Outcome Measures in Rheumatology (OMERACT) initiative was launched in 2004 to develop a composite index ['virtual total joint replacement' (VJR)] as a surrogate outcome for osteoarthritis (OA) progression in DMOAD RCTs. Our objective was to evaluate the prevalence of patients fulfilling different thresholds of sustained pain, reduced function, and X-ray change in existing DMOAD RCTs.
DESIGN
Post hoc analysis of summary data from the placebo arm of eight DMOAD RCTs.
RESULTS
Eight OA RCTs representing 1379 patients were included. Pain was assessed by WOMAC and/or VAS and function by WOMAC and/or Lequesne. Among six knee and two hip studies, 248 (22%) and 132 (51%) patients respectively had X-ray progression [decrease joint space width (JSW) ≥0.5 mm]. The prevalence of patients fulfilling clinical and radiographic criteria was highest (n = 163, 12%) in the least stringent scenario (pain + function ≥80 at ≥2 visits); with few patients (n = 129, 2%) in the most stringent scenario (pain + function ≥80 at ≥4 visits). Using these prevalence data, a sample size of 352-2144 per group would be needed to demonstrate a 50% difference between groups.
CONCLUSIONS
The prevalence of patients with sustained symptomatic OA of at least a moderate degree with X-ray progression is low. Even using lenient criteria to define VJR, large patient numbers would be required to detect differences between groups in DMOAD RCTs. Investigation of the optimal cutoff threshold and combination of symptoms and radiographic change should be pursued. | 10.1016/j.joca.2011.11.013 |
pubmed_476_5094 | New lineages of SARS-CoV-2 are constantly emerging. They contain mutations in the spike glycoprotein that can affect virus infectivity, transmissibility, or sensitivity to vaccine-elicited antibodies. Here we show that the emergence of new spike variants is accurately predicted by patterns of amino acid variability (volatility) in small virus clusters that phylogenetically-precede or chronologically-predate such events. For each spike position, volatility within the virus clusters, volatility at adjacent positions on the three-dimensional structure of the protein, and volatility across the network of co-volatile sites describe its likelihood for mutations. By combining these variables, early-pandemic sequences accurately forecasted mutations in lineages that appeared 6-13 months later. The patterns of mutations in variants Alpha and Delta, as well as the recently-appearing variant Omicron were also predicted remarkably well. Importantly, probabilities assigned to spike positions for within-lineage mutations were lineage-specific, and accurately forecasted the observed changes. Sufficient antecedent warning of the imminent changes in SARS-CoV-2 lineages will allow design of immunogens that address their specific antigenic properties.
SIGNIFICANCE
New variants of SARS-CoV-2 continue to emerge in the population. Due to mutations in the spike protein, some variants exhibit partial resistance to therapeutics and to the immunity provided by COVID-19 vaccines. Thus, there is a need for accurate tools to forecast the appearance of new virus forms in the population. Here we show that patterns of amino acid variability across the spike protein accurately predict the mutational patterns that appeared within SARS-CoV-2 lineages with considerable advance warning time. Interestingly, mutation probabilities varied greatly between lineages, most notably for critical sites in the receptor-binding domain of spike. The high predictive capacity of the model allows design of vaccines that address the properties of variants expected to emerge in the future. | 10.1101/2022.02.01.478697 |
pubmed_269_14278 | BACKGROUND
The proportion of energy from free sugars and saturated fat currently exceeds the UK-recommended intake across all age groups. Recognising the limits of reformulation programmes, the government in England has announced their intention to introduce legislation to restrict the promotion of foods high in free sugars, salt, and saturated fats in prominent store locations. Here, we evaluated a grocery store intervention to remove seasonal confectionery from prominent locations within a major UK supermarket.
METHODS AND FINDINGS
A nonrandomised controlled intervention study with interrupted time series (ITS) analysis was used. Data were analysed from 34 intervention stores located in 2 London boroughs and 151 matched control stores located elsewhere in the UK owned by the same retailer. Stores were matched based on store size and overall sales during the previous year. Between 15 February 2019 and 3 April 2019 (before Easter), stores removed free-standing promotional display units of seasonal confectionery from prominent areas, although these products were available for purchase elsewhere in the store. Store-level weekly sales (units, weight (g), and value (£)) of seasonal chocolate confectionery products were used in primary analyses, with data from 1 January 2018 to 24 November 2019. Secondary outcomes included total energy, fat, saturated fat, and sugars from all in-store purchases. Multivariable hierarchical models were used to investigate pre/post differences in weekly sales of confectionery in intervention versus control stores. ITS analyses were used to evaluate differences in level and trends after intervention implementation. Over a preintervention baseline period (15 February 2018 to 3 April 2018), there were no significant differences in sales (units, weight, and value) of all chocolate confectionery between intervention versus control stores. After intervention implementation, there was an attenuation in the seasonal increase of confectionery sales (units) in intervention stores compared to control (+5% versus +18%; P < 0.001), with similar effects on weight (g) (+12% versus +31%; P < 0.001) and value (£) (-3% versus +10%; P < 0.001). ITS analyses generally showed statistically significant differences in the level at the point of intervention (P ranges 0.010 to 0.067) but also in the trend afterwards (P ranges 0.024 to 0.053), indicating that the initial difference between intervention and control stores reduced over time. There was a significant difference in level change in total energy sold, adjusted for the total weight of food and drink (kcal/g, P = 0.002), and total fat (fat/g) (P = 0.023), but no significant changes in saturated fat or sugars from total sales in ITS models. There was no evidence that the main results varied across store deprivation index. The limitations of this study include the lack of randomisation, residual confounding from unmeasured variables, absolute differences in trends and sales between intervention versus control stores, and no independent measures of intervention fidelity.
CONCLUSIONS
Removal of chocolate confectionery from prominent locations was associated with reduced purchases of these products, of sufficient magnitude to observe a reduction in the energy content of total food purchases. These results from a "real-world" intervention provide promising evidence that the proposed legislation in England to restrict promotions of less healthy items in prominent locations may help reduce overconsumption.
TRIAL REGISTRATION
https://osf.io/br96f/. | 10.1371/journal.pmed.1003951 |
pubmed_623_6206 | The world is facing a new pandemic in progress due to a mosquito-borne flavivirus popularly known as Zika virus. The emergence of this new virus is really alarming with the sudden increment in the cases of microcephaly reported from Brazil. The findings attributing the involvement of Zika virus as the reason for congenital deformations in the babies born in afflicted areas have really shocked the world. The present knowledge about this virus is very limited and in the absence of further studies the precautions seems to be the best way of protection from this virus. The present article is a short review about this new virus. | 10.7860/JCDR/2016/19170.8133 |
pubmed_670_662 | Vasopressin (VP) was administered in the lateral cerebral ventricles of homozygous rats with congenital diabetes insipidus of Brattleboro (BB) strain as well as of normal animals of Long Evans strain (LE). The following parameters were studied: the latent period for achievement of maximal pressor response in seconds (LP), absolute value of the increase in arterial pressure in comparison with the initial V mmHg (delta AP) and cardiac frequency (CF). The initial values of AP in BB were lower than those values found in LE (BB-9, 10 +/- 0.57 kPa; LE-11, 31 +/- 0.53 kPa; p less than 0.01, while CF showed higher values in BB (350 +/- 8.5 min-1); LE (321 +/- 10 min-1); p less than 0.05. VP, administered intraventricularly, induced quick transitory elevation of AP in both groups, which did not differ substantially both in respect to LP (BB-55 +/- 11 s; LE-43 +/- 6.9) and also in respect to delta AP (BB-3.64 +/- 0.34; LE-3.14 +/- 0.62). CF was not changed in BB (347 +/- 8.9), while it was slightly increased in LE (334 +/- 11). The data show that exogenously administered VP affect the central VP-dependent mechanisms for regulation of AP in the same way in both groups of rats. | pubmed_670_662 |
pubmed_174_2608 | Surface preparations of the stria vascularis from guinea pigs exposed to wide-band noise or intoxicated with quinine monohydrochloride dihydrate were studied by light microscopy and computerized image analysis in order to evaluate quantitatively the effects of these agents on two characteristics of the strial vasculature: vascular density and erythrocyte distribution. An image analyzer was used to measure the area of strial vessel lumen and erythrocyte distribution as a fraction of the total area of strial tissue under observation. The results demonstrate that changes in the strial vessels do occur in guinea pigs exposed to noise or given large doses of quinine. Localized vessel narrowings caused by swollen endothelial cells and possibly by contraction of pericytes were found in both experimental groups, but there was no apparent tonotopical relationship between these effects and the reduction in cochlear potentials. A significant reduction in the number of erythrocytes was found in all turns of the cochlea in both experimental groups. Although a significant difference in vascular density was found among turns of the cochlea in both experimental and control animals, there was no widespread change in vascular density as a result of either noise exposure or quinine treatment. | 10.1016/s0196-0709(85)80056-9 |
pubmed_851_23092 | Fetal right ventricular (RV) prominence is a known indicator of possible left-sided structural heart disease with a low positive predictive value for aortic coarctation. There is a paucity of data on identifying which fetuses with RV prominence will have postnatal arch obstruction. Our study objectives were to create a clinical prediction tool for coarctation and to describe the diagnostic outcomes of our cohort with fetal RV prominence. We performed a retrospective review of patients referred with fetal RV prominence from January 2009 to October 2015. Recorded fetal echocardiographic variables included gestational age, semilunar and atrioventricular valve dimensions, left and right ventricular mid-cavitary dimensions, foramen ovale and aortic arch flow direction, and isthmal diameter. Postnatal cardiac and non-cardiac diagnoses were documented. We performed descriptive analysis for postnatal outcomes and classification tree analysis to create a clinical prediction tool. Eighty-eight patients were reviewed; 58 (66%) had abnormal postnatal echocardiograms, 45 (51%) had left-sided lesions, including 26 (30%) with coarctation, and 6 (7%) had pulmonary hypertension. Our clinical prediction tool employs gestational age, RV mid-cavitary dimension z-score, and isthmal diameter z-score to predict coarctation with 85% accuracy, 95% confidence interval [75.3, 92.4%]. Our model correctly classified 45/54 non-coarctation and 19/21 coarctation cases, with 90% sensitivity and 83% specificity. Developing an accurate prediction tool for coarctation in cases of fetal RV prominence is an important first step in improving our management of these challenging cases. | 10.1007/s00246-017-1686-6 |
pubmed_1048_20222 | INTRODUCTION
Medications that interfere with sympathetic neuronal norepinephrine uptake and storage, such as neuropsychiatrics (NP) and sympathomimetic amines, are most likely to affect cardiac uptake of iodine-123 metaiodobenzylguanidine (I-mIBG). The present study examined these and other medications reported to affect I-mIBG uptake using measurements of cardiac I-mIBG uptake on the heart failure (HF) patients in the ADMIRE-HF extension (X) study.
METHODS
Baseline concomitant medications taken by the 961 HF patients were categorized into five groups: calcium channel blockers, NP medications, β agonists and sympathomimetics, α antagonists, and other antihypertensives. NP medications were further subcategorized into those expected to have high and low impact on norepinephrine transporter (NET) function. Myocardial I-mIBG heart/mediastinum (H/M) uptake ratios on 4 h planar images were compared among the groups. Impact of medication group on the prognostic value of the H/M ratio for all-cause (AC) and cardiac death during a median 2-year follow-up was also examined.
RESULTS
A total of 283 (29%) patients were using at least one calcium channel blocker, NP medication, or β agonist or sympathomimetic. These patients had a lower mean H/M ratio than the other study patients (1.42±0.20 vs. 1.45±0.20; P=0.022). However, the 2-year AC mortality rates in the two groups were the same [11.3% (95% confidence interval: 7.5-15.2%) vs. 11.8% (95% confidence interval: 9.2-14.4%)]. In terms of medication categories, there were no significant differences in the mean H/M ratios between patients who did and did not use NP medications, β agonists, calcium channel blockers, and α antagonists. Across all categories, patients with H/M ratio greater than or equal to 1.60 had lower AC and cardiac mortality. Patients using higher potency (for NET inhibition) NP medications had significantly lower H/M ratio values, but the prognostic significance of H/M ratio greater than or equal to 1.60 was unchanged.
CONCLUSION
Only a small number of higher potency NET-inhibiting NP medications have a measurable effect on the results of I-mIBG myocardial imaging. There appears to be no basis for restricting the use of calcium channel blockers and β agonist respiratory medications in HF patients referred for cardiac I-mIBG imaging. | 10.1097/MNM.0000000000000619 |
pubmed_964_5107 | We examined the relationship between the amino acid sequences of the V2 and V3 regions of the envelope protein and the biological properties of ten human immunodeficiency virus type 1 (HIV-1) primary isolates. The infectivity, cytopathic effect (CPE), and syncytium forming activity of these primary isolates were tested against three T cell lines (CEM, MT2, and MOLT4/CL.8 cells), CD8-depleted peripheral blood mononuclear cells (PBMC), and primary monocyte-derived macrophages (MDM) from seronegative donors. In addition to the viral groups which had the syncytium inducing/T-cell line tropic (SI/TT) phenotype or non-syncytium inducing/non-T cell line tropic (NSI/NT) phenotype (including the NSI/macrophage tropic (NSI/MT) phenotype), there was a group of viruses that infected one or two T cell lines and PBMC but could not mediate syncytium formation. We therefore classified this group of viruses as a non-syncytium inducing/partial T-cell line tropic (NSI/pTT) virus. To investigate the relationship between these viral phenotypes and the sequence variability of the V2 and V3 regions of the envelope, we cloned the viral gene segment and sequenced the individual isolates. The sequence data suggested that the SI/TT type changes in the V3 sequence alone mediate a partial T cell line tropism and mild cytopathic effect and that an isolate became more virulent (SI/TT phenotype) if there were additional changes in the V2 or other regions. On the other hand, sequence changes in the V2 region alone could not mediate phenotypic changes but some additional changes in the other variable regions (for example, V3) might be required for the phenotypic changes in combination with changes in V2. These findings also suggested that amino acid changes in both the V2 and V3 region are required for the development of virulent variants of HIV-1 that outgrow during advanced stages of the disease. | 10.1111/j.1348-0421.1996.tb03347.x |
pubmed_596_2488 | This study examined the local structural properties of CuI at low temperatures of 10-300 K by x-ray diffraction (XRD) and extended x-ray absorption fine structure (EXAFS) measurements at the Cu K edge. The XRD data were refined using two models, split (distorted zinc-blende structure) and non-split (zinc-blende structure), using a conventional Rietveld refinement combined with a maximum entropy method (MEM). MEM/Rietveld analyses showed that both the split and non-split models could fit the data. EXAFS revealed the split model fit to be better than the non-split model. The split distance of Cu-I pairs was approximately 0.03 Å at 15 K and increased to 0.07 Å at 300 K. XRD and EXAFS combined together suggested that the CuI crystal was in a metastable state with a distorted zinc-blende structure at low temperatures. | 10.1088/0953-8984/23/17/175402 |
pubmed_794_12205 | Damping performance of the plates with constrained layer damping (CLD) treatment mainly depends on the layout of CLD material and the material physical properties of the viscoelastic damping layer. This paper develops a concurrent topology optimization methodology for maximizing the modal loss factor (MLF) of plates with CLD treatment. At the macro scale, the damping layer is composed of 3D periodic unit cells (PUC) of cellular viscoelastic damping materials. At the micro scale, due to the deformation of viscoelastic damping material affected by the base and constrained layers, the representative volume element (RVE) considering a rigid skin effect is used to improve the accuracy of the effective constitutive matrix of the viscoelastic damping material. Maximizing the MLFs of CLD plates is employed as the design objectives in optimization procedure. The sensitivities with respect to macrodesign variables are formulated using the adjoint vector method while considering the contribution of eigenvectors, while the influence of macroeigenvectors is ignored to improve the computational efficiency in the mesosensitivity analysis. The macro and meso scales design variables are simultaneously updated using the Method of Moving Asymptotes (MMA) to find concurrently optimal configurations of constrained and viscoelastic damping layers at the macro scale and viscoelastic damping materials at the micro scale. Two rectangular plates with different boundary conditions are presented to validate the optimization procedure and demonstrate the effectiveness of the proposed concurrent topology optimization approach. The effects of optimization objectives and volume fractions on the design results are investigated. The results indicate that the optimized layouts of the macrostructure are dependent on the objective mode and the volume fraction on the meso scale. The optimized designs on the meso scale are mainly related to the objective mode. By varying the volume fraction on the macro scale, the optimized designs on the meso scale are different only in their detailed size, which is reflected in the values of the equivalent constitutive matrices. | 10.3390/ma15103512 |
pubmed_440_6850 | Are small molecules or biologics the drugs of the future? Small-molecule drugs have historically been the pillars of traditional medicine. However, recently, we seem to be amidst a scientific revolution with the rise of many FDA-approved biologic drugs. This opinion article looks at the current state of small molecules and biologics and assesses what the future holds for these two broad classes of drugs. | 10.1039/c8md90019a |
pubmed_157_5487 | BACKGROUND
Smoking is a global public health problem. For this reason, experts have called smoking dependence a global epidemic. Over the past 5 years, sales of electronic cigarettes, or e-cigarettes, have been growing strongly in many countries. Yet there is only partial evidence that e-cigarettes are beneficial for smoking cessation. In particular, although it has been proven that nicotine replacement devices may help individuals stop smoking and tolerate withdrawal symptoms, e-cigarettes' power to increase the quitting success rate is still limited, ranging from 5% to 20% dependent on smokers' baseline conditions as shown by a recent Cochrane review. Consequently, it is urgent to know if e-cigarettes may have a higher success rate than other nicotine replacement methods and under what conditions. Furthermore, the effects of the therapeutic setting and the relationship between individual characteristics and the success rate have not been tested. This protocol is particularly innovative, because it aims to test the effectiveness of electronic devices in a screening program (the COSMOS II lung cancer prevention program at the European Institute of Oncology), where tobacco reduction is needed to lower individuals' lung cancer risks.
OBJECTIVE
This protocol was designed with the primary aim of investigating the role of tobacco-free cigarettes in helping smokers improve lung health and either quit smoking or reduce their tobacco consumption. In particular, we aim to investigate the impact of a 3-month e-cigarettes program to reduce smoking-related respiratory symptoms (eg, dry cough, shortness of breath, mouth irritation, and phlegm) through reduced consumption of tobacco cigarettes. Furthermore, we evaluate the behavioral and psychological (eg, well-being, mood, and quality of life) effects of the treatment.
METHODS
This is a prospective, randomized, placebo-controlled, double-blind, three-parallel group study. The study is organized as a nested randomized controlled study with 3 branches: a nicotine e-cigarettes group, a nicotine-free e-cigarettes group, and a control group. The study is nested in a screening program for early lung cancer detection in heavy smokers.
RESULTS
The study is open and is still recruiting.
CONCLUSIONS
Stopping or reducing tobacco consumption should be a main goal of any health organization. However, traditional antismoking programs are expensive and not always effective. Therefore, favoring a partial or complete shift to e-cigarettes in heavy smokers (eg, persons at high risk for a number of diseases) could be considered a moral imperative. However, before following this path, sound and reliable data on large samples and in a variety of contexts are required.
TRIAL REGISTRATION
Clinicaltrials.gov NCT02422914; https://clinicaltrials.gov/ct2/show/NCT02422914 (Archived by WebCite at http://www.webcitation.org/6etwz1bPL). | 10.2196/resprot.4805 |
pubmed_859_10649 | BACKGROUND/OBJECTIVES
Exome sequencing may identify pathogenic variants unrelated with the purpose of the analysis. We investigated the frequency of secondary and incidental findings (SF/IF) in cancer susceptibility genes (CSG), their clinical actionability and the psychological impact in individuals with an SF/IF (cases) compared with individuals tested due to their cancer history (controls).
METHODS
This study analysed 533 exomes ordered for non-cancer conditions. Medical records were reviewed for clinical actionability of SF/IF. Psychological impact was analysed using the Multidimensional Impact of Cancer Risk Assessment (MICRA) scale and compared between cases and controls with a propensity score weighting method.
RESULTS
The frequency of SF/IF in CSG was 2.1% (95% CI 1.1% to 3.8%): three BRCA2, three PMS2, two SDHB, and one each in BRCA1, MLH1 and RAD51C. Among the relatives, 18 were carriers. Twenty enrolled for surveillance, and a neoplasm was diagnosed in 20%: three paragangliomas and one breast cancer. Cases presented higher MICRA mean scores than controls (21.3 vs 16.2 in MICRA total score, 6.3 vs 4.2 in the distress subscale, and 8.3 vs 6.6 in the uncertainty subscale; all p<0.001).
CONCLUSION
SF/IF in CSG were identified in 2.1% of patients. Despite a numerically higher psychological impact, the identification of SF/IF allowed early detection and cancer prevention in families without cancer history. | 10.1136/jmg-2022-108929 |
pubmed_965_11599 | Antimony(V) is volatilized by reaction with potassium bromide in concentrated sulfuric acid media. After volatilization, the gases can be transported to an inductively coupled plasma spectrometer for atomic emission of antimony and its analytical determination. The influent factors, concentrated sulfuric acid volume, concentration and volume of the potassium bromide aqueous solution and carrier gas flow were investigated and optimized using different alternatives. A detection limit of 48ngml(-1) of Sb was achieved under the optimized conditions with a precision of 7.6% and the calibration graph was linear from 0.10 to 10.0mugml(-1) for a sample injection of 130mul. The study of interferences from common cations and anions revealed a good tolerance for most ions, although there was a significant improvement in Sb(V) volatility when As(III) was present. Furthermore, the As(III) sensitization was only produced with Sb(V) species, while the volatility of the Sb(III) bromide species was unaltered. The method was applied to the determination of Sb in real river waters. The results were checked using alternative atomic spectroscopy methods. | 10.1016/j.talanta.2004.12.063 |
pubmed_651_4135 | MDL 17,043 administered intravenously or orally exerts positive inotropic and vasodilator actions in experimental animal preparations. We studied its acute hemodynamic effects in 15 patients with severe congestive heart failure by right-heart catheterization. Intravenous MDL 17,043 at 10 minutes increased cardiac index (3.4 +/- 0.8 vs 1.9 +/- 0.4 l/min/m2), narrowed arteriovenous oxygen content difference (4.6 +/- 0.8 vs 7.8 +/- 2.0 vol%), increased heart rate (98 +/- 14 vs 89 +/- 18 beats/min), and decreased systemic arterial (67 +/- 10 vs 83 +/- 11 mm Hg), pulmonary capillary wedge (12 +/- 5 vs 24 +/- 5 mm Hg) and right atrial (6 +/- 5 vs 12 +/- 7 mm Hg) mean pressures significantly (p less than 0.001). In 11 patients, hemodynamics were monitored hourly for 6 hours. Compared with baseline, the cardiac index and heart rate were higher and mean systemic arterial pressure was lower for 6 hours; pulmonary capillary and right atrial mean pressures were significantly lower for 5 hours. No serious arrhythmias or side effects occurred. These data suggest that MDL 17,043 may be useful for treating congestive heart failure. | 10.1161/01.cir.67.4.823 |
pubmed_336_8336 | Biotic and abiotic factors have been proposed to explain patterns of reproductive character displacement, but which factor is most important to character displacement of acoustic signals is not clear. Male vocalizations of the frog Pseudacris feriarum are known to undergo reproductive character displacement in areas of sympatry with P. brimleyi and P. nigrita. Despite evidence for reinforcement as an important mechanism, local adaptation via sensory drive might explain this pattern because Pseudacris breed in different habitat types and mating signals are exposed to a variety of environments. We tested the sensory drive hypothesis by playing synthesized vocalizations representing the spectrum of variation in P. feriarum at 12 different study sites. If sensory drive has occurred, then vocalizations should transmit better in the site of origin or at ecologically similar sites. We found that variation in acoustic signals did not produce better transmission in particular sites, the effect of site was uniform, and acoustic signals often transmitted better in habitats external to their origin. Ecological variation among habitats did not explain signal degradation. Our playback experiments, ecological analyses, and comparisons of different habitat types provide no support for sensory drive as a process promoting reproductive character displacement in this system. Reinforcement is the more likely primary mechanism. | 10.1111/evo.12366 |
pubmed_1046_2710 | Pride is a status-related self-conscious emotion. The present study aimed to investigate the nature of status behind pride in four studies with using the two-facet model of pride, status maintenance strategies and with differentiating subjective social status (SSS) and objective social status (OSS). In Studies 1 and 2, we used questionnaire methods with structural equation modeling (SEM) in order to identify the relationship patterns between SSS, OSS, status maintenance strategies and pride. In Studies 3 and 4, we used vignette method and SEM to identify these links. All four studies gave evidence for the SSS → prestige status maintenance strategy → authentic pride relationship pattern. Similarly consistent result was found regarding the dominance status maintenance strategy → hubristic pride link. Depending on the assessment method (questionnaire vs. vignette) and the evaluative frame of reference (self vs. other), OSS was related to either authentic and hubristic pride, only hubristic pride, or neither of them. Based on these results, one thing can be taken for granted: pride is a subjective status-related emotion. However, the present results suggest that it is not necessarily true for OSS. | 10.3389/fpsyg.2018.01979 |
pubmed_353_726 | The National Animal Germplasm Program (NAGP) is developing a national repository for germplasm (semen, oocytes, embryos, blood, DNA, tissue) for all agricultural species in the US. Currently, the swine collection consists of 127,479 samples from 886 boars representing 20 major, minor and composite populations. Cryopreservation per se is not an impediment to program success. Rather, the greatest difficulties encountered are in determining the quality of the samples pre- and post-thaw. Robust, broadly applicable, and cost effective quality control methodologies need to be developed and implemented. This overview of the NAGP will discuss the approaches used for cryopreserving boar semen samples, overcoming the challenges of assessing sample quality, and moving toward a quality control strategy. | 10.1016/j.theriogenology.2008.06.012 |
pubmed_590_5199 | Hypoglycemia in apparently healthy adults is a rare finding in clinical practice requiring a thorough investigation of the cause. During the investigation, identification of hypoglycemia associated with inappropriately high levels of insulin and C-peptide should prompt the exclusion of rare causes of hypoglycemia, including pancreatic islet-cells disease and autoimmune hypoglycemia. In this paper, we describe two cases of hypoglycemia associated with endogenous hyperinsulinism, whose causes are uncommon in clinical practice, and review important aspects of the diagnosis and treatment of hyperinsulinemic hypoglycemia. | pubmed_590_5199 |
pubmed_494_2796 | Retroviral vectors are transcriptionally silent in pluripotent stem cells. This feature has been potently applied in studies that reprogram somatic cells into induced pluripotent stem (iPS) cells. By delivering the four Yamanaka factors in retroviral vectors, high expression is obtained in fibroblasts to induce the pluripotent state. Partial reprogramming generates Class I iPS cells that express the viral transgenes and endogenous pluripotency genes. Full-reprogramming in Class II iPS cells silences the vectors as the endogenous genes maintain the pluripotent state. Thus, retroviral vector silencing serves as a beacon marking the fully reprogrammed pluripotent state. Here we review known silencer elements, and the histone modifying and DNA methylation pathways, that silence retroviral and lentiviral vectors in pluripotent stem cells. Both retroviral and lentiviral vectors are influenced by position effects and often exhibit variegated expression. The best vector designs facilitate full-reprogramming and subsequent retroviral silencing, which is required for directed-differentiation. Current retroviral reprogramming methods can be immediately applied to create patient-specific iPS cell models of human disease, however, future clinical applications will require novel chemical or other reprogramming methods that reduce or eliminate the integrated vector copy number load. Nevertheless, retroviral vectors will continue to play an important role in genetically correcting patient iPS cell models. We anticipate that novel pluripotent-specific reporter vectors will select for isolation of high quality human iPS cell lines, and select against undifferentiated pluripotent cells during regenerative medicine to prevent teratoma formation after transplantation. | 10.1002/jcb.21912 |
pubmed_202_14567 | While it is no longer possible to imagine the treatment of an acute transmural myocardial infarction without the use of thrombolytic agents, some discussion still exists as to the choice of the thrombolytic agent. Our study concerns a group of 160 patients with an acute transmural myocardial infarction, 60 of whom were treated with anistreplase, 52 with streptokinase and 48 with alteplase. Statistically, the administration of anistreplase was associated with a significantly higher frequency of ventricular arrhythmias in comparison to the other thrombolytic agents, whereas after subsequent coronary angiography, the anistreplase group revealed a significantly lower number of completely occluded coronary arteries. The data from this study demonstrate that anistreplase is a very valuable thrombolytic agent. It may even be more effective than streptokinase and alteplase in the treatment of acute myocardial infarction when the patency of the coronary arteries 1 month after the acute coronary event is considered the primary endpoint. | 10.1536/ihj.33.413 |
pubmed_379_3786 | The clinical, radiographic and endoscopic findings in 16 patients with ischaemic colitis, all of whom were < 45 years of age, were analysed. The clinical features were characterized by an acute onset of abdominal pain and rectal bleeding, and persistent constipation prior to the onset of symptoms. Twelve of the 16 patients did not have any known predisposing factors. Barium enema examination and colonoscopy revealed longitudinal ulcers and oedema of the left side of the colon of these patients. These features were then compared with those found in patients with ischaemic colitis, who were > 70 years of age. Although the clinical symptoms, the site of involvement and the initial radiographic or endoscopic findings were similar between the two groups, the transient form of ischaemic colitis and constipation prior to the onset of symptoms were more frequently present in the young patients than in the old patients. These findings suggest that ischaemic colitis, which is not a rare condition even in young adults, is less severe in young patients than in old patients, and that constipation may be related to the pathogenesis of this disease in young adults. | 10.1111/j.1440-1746.1994.tb01563.x |
pubmed_115_7724 | We present a probabilistic framework--namely, multiscale generative models known as Dynamic Trees (DT)--for unsupervised image segmentation and subsequent matching of segmented regions in a given set of images. Beyond these novel applications of DTs, we propose important additions for this modeling paradigm. First, we introduce a novel DT architecture, where multilayered observable data are incorporated at all scales of the model. Second, we derive a novel probabilistic inference algorithm for DTs--Structured Variational Approximation (SVA)--which explicitly accounts for the statistical dependence of node positions and model structure in the approximate posterior distribution, thereby relaxing poorly justified independence assumptions in previous work. Finally, we propose a similarity measure for matching dynamic-tree models, representing segmented image regions, across images. Our results for several data sets show that DTs are capable of capturing important component-subcomponent relationships among objects and their parts, and that DTs perform well in segmenting images into plausible pixel clusters. We demonstrate the significantly improved properties of the SVA algorithm--both in terms of substantially faster convergence rates and larger approximate posteriors for the inferred models--when compared with competing inference algorithms. Furthermore, results on unsupervised object recognition demonstrate the viability of the proposed similarity measure for matching dynamic-structure statistical models. | 10.1109/TPAMI.2005.219 |
pubmed_840_17387 | Magnetic resonance imaging of the breast is useful in assessing breast lesions. An understanding of the pathologic characteristics of the tumors may help to understand these magnetic resonance imaging observations.Large lesional size (>10 mm), ill-defined margin, and irregular outlines are associated with malignancy. These correlate with the pathological features of breast tumor, characterized by rapid growth rate, large size, and infiltrative growth pattern, invasion into stroma resulting in desmoplasia, and hence irregular outline and margin. The detection and estimation of tumor extent of invasive lobular carcinoma is problematic, even with magnetic resonance imaging, which is considered the most sensitivity. This inaccuracy likely derives from the characteristic linear, single cells infiltration growth pattern of the tumor, which is also often underestimated by clinical examination. Estimation of tumor extent after neoadjuvant chemotherapy is also essential but problematic by imaging, as the shrunken tumor becomes fibrotic, with stromal hyalinization, diminished microvasculature and tumor break up causing size underestimation. Non-enhancement of breast tumors occurs in about 8% of cases correlates with diffuse growth pattern, particularly of infiltrative lobular carcinoma. The observation of disproportionately high non-enhancing ductal carcinoma in situ remains an enigma. Finally, early rim enhancement correlates with small cancer nests, low ratio of peripheral to central fibrosis and high ratio of peripheral to central microvessel density. These may be related to increased vascular endothelial growth factor mediated increased microvessel density as well as increased permeability, which manifest as increased rapid contrast uptake and dissipation. | 10.1007/s10549-006-9352-3 |
pubmed_876_11846 | X-ray absorption fine structure (XAFS) measurements unambiguously establish the structure of the active centers in high-performance Ti-SiO2 epoxidation catalysts. Subtleties in structural changes in proceeding from the dispersed titanocene dichloride precursor to the anchored Ti(IV) centers are charted, in situ, by both near-edge (XANES) and extended-edge (EXAFS) measurements. The active centers are tripodally attached titanol groups: (Si-O)3-TiOH. These permit facile expansion of the coordination shell (also monitored by in situ XAFS studies) during catalysis, and thereby lead to the formulation of a plausible mechanism of epoxidation of alkenes that is consonant with recent DFT computations. Previously proposed mechanisms, based on a three-coordinated titanyl group (as well as possible five- or six-coordinated active sites), are discounted. Comparable XAFS studies of soluble catalytically active four-coordinated Ti(IV)-containing molecular entities establish that the heterogeneous Ti-SiO2 catalyst has "single-site" active centers. Equipped with such information, minute changes in hydrophobicity and local composition (e.g., replacement of one Si by a Ge) can be wrought so as to boost the performance of the catalyst. The merits of using combined in situ X-ray absorption spectroscopic and X-ray diffractometric measurements are also highlighted. | 10.1021/ar010003w |
pubmed_631_25454 | Handedness and brain asymmetry are widely regarded as unique to humans, and associated with complementary functions such as a left-brain specialization for language and logic and a right-brain specialization for creativity and intuition. In fact, asymmetries are widespread among animals, and support the gradual evolution of asymmetrical functions such as language and tool use. Handedness and brain asymmetry are inborn and under partial genetic control, although the gene or genes responsible are not well established. Cognitive and emotional difficulties are sometimes associated with departures from the "norm" of right-handedness and left-brain language dominance, more often with the absence of these asymmetries than their reversal. | 10.1371/journal.pbio.1001767 |
pubmed_61_20008 | In this paper, molecularly imprinted polymer (MIP) of isoniazid is synthesized through thermal radical copolymerization of metharylic acid (MAA) and ethylene glycol dimethacrylate (EGDMA) in the presence of isoniazid template molecules. A novel flow injection chemiluminescence sensor for isoniazid determination is developed by packing the isoniazid-MIP into the flow cell as recognition elements. Isoniazid could be selectively adsorbed by the MIPs and the adsorbed isoniazid was sensed by its great enhancing effect on the weak CL reaction between luminol and periodate which were mixed in the flow cell. The enhanced CL intensity is linear in the range 2x10(-9) to 2x10(-7) g/mL and the detection limit is 7x10(-10) g/mL (3sigma) isoniazid with a relative standard deviation 2.8% (n=9) for 8x10(-8) g/mL. The sensor is reversible and reusable. It has a great improvement in sensitivity and selectivity for CL analysis. As a result, the sensor has been successfully applied to determination of isoniazid in human urine. At the same time, the binding characteristic of the polymer to isoniazid was evaluated by batch method and the dynamic method, respectively. | 10.1016/j.saa.2006.03.001 |
pubmed_490_22682 | Aquablation is a novel technique for the surgical management of bladder outlet obstruction secondary to benign prostatic hyperplasia. Following first-in-man studies, a multicenter trial was conducted with results now out to 1 year. Aquablation resulted in a mean International Prostate Symptom Score improvement of 16 points (p < 0.01) and a mean maximum urinary flow rate increase from 8.7 to 18.3 ml/s (p < 0.01) at 12 months. Due to the precise prostate mapping, aquablation has also demonstrated favorable sexual and urinary outcomes with no new erectile dysfunction, retrograde ejaculation, or urinary incontinence as often experienced with other techniques. These improvements in functional outcomes at 12 months confirm that aquablation is a safe and effective alternative for BPH treatment. | 10.1007/s11934-017-0743-2 |
pubmed_173_22046 | Studies of expression quantitative trait loci (eQTLs) offer insight into the molecular mechanisms of loci that were found to be associated with complex diseases and the mechanisms can be classified into cis- and trans-acting regulation. At present, high-throughput RNA sequencing (RNA-seq) is rapidly replacing expression microarrays to assess gene expression abundance. Unlike microarrays that only measure the total expression of each gene, RNA-seq also provides information on allele-specific expression (ASE), which can be used to distinguish cis-eQTLs from trans-eQTLs and, more importantly, enhance cis-eQTL mapping. However, assessing the cis-effect of a candidate eQTL on a gene requires knowledge of the haplotypes connecting the candidate eQTL and the gene, which cannot be inferred with certainty. The existing two-stage approach that first phases the candidate eQTL against the gene and then treats the inferred phase as observed in the association analysis tends to attenuate the estimated cis-effect and reduce the power for detecting a cis-eQTL. In this article, we provide a maximum-likelihood framework for cis-eQTL mapping with RNA-seq data. Our approach integrates the inference of haplotypes and the association analysis into a single stage, and is thus unbiased and statistically powerful. We also develop a pipeline for performing a comprehensive scan of all local eQTLs for all genes in the genome by controlling for false discovery rate, and implement the methods in a computationally efficient software program. The advantages of the proposed methods over the existing ones are demonstrated through realistic simulation studies and an application to empirical breast cancer data from The Cancer Genome Atlas project. | 10.1080/01621459.2015.1038449 |
pubmed_240_9157 | Sol-gel entrapment is an efficient immobilization technique that allows preparation of robust and highly stable biocatalysts. Lipase from Candida antarctica B was immobilized by sol-gel entrapment and by sol-gel entrapment combined with adsorption on Celite 545, using a ternary silane precursor system. After optimization of the immobilization protocol, the best enzyme loading was 17.4 mg/g support for sol-gel entrapped lipase and 10.7 mg/g support for samples obtained by entrapment and adsorption. Sol-gel immobilized enzymes showed excellent values of enantiomeric ratio E and activity when ionic liquid 1-octyl-3-methyl-imidazolium tetrafluoroborate was used as additive. Immobilization increased the stability of the obtained biocatalysts in several organic solvents. Excellent operational stability was obtained for the immobilized lipase, maintaining unaltered catalytic activity and enantioselectivity during 15 reuse cycles. The biocatalysts were characterized using scanning electron microscopy (SEM) and fluorescence microscopy. The improved catalytic efficiency of entrapped lipases recommends their application for large-scale kinetic resolution of optically active secondary alcohols. | 10.3390/molecules171113045 |
pubmed_348_24965 | BACKGROUND AND PURPOSE
The reported MR imaging characteristics of cavernous sinus cavernous hemangiomas (CSCHs) in the literature are nonspecific. The purpose of our study was to explore dynamic enhancement features of CSCHs on conventional contrast-enhanced MR imaging and to correlate these features with histopathologic subtypes.
MATERIALS AND METHODS
Twenty-one patients (8 male and 13 female; age range, 13-63 years; average age, 42.6 years) with surgically confirmed CSCHs were retrospectively investigated. Preoperative MR study was performed in all cases, consisting of T1-weighted axial imaging, T2-weighted axial imaging, T1-weighted sagittal imaging, and contrast-enhanced T1-weighted axial, sagittal, and coronal images.
RESULTS
There were 4.8% (1/21) that showed homogeneous enhancement on all 3 contrast-enhanced sequences, whereas 95.2% (20/21) demonstrated heterogeneous enhancement on the first contrast-enhanced sequence. Among the 20 lesions, on subsequent contrast-enhanced sequences, 55.0% (11/20) showed homogeneous enhancement, whereas 35.0% (7/20) of lesions showed progressive contrast "filling in." The remaining 10% (2/20) exhibited no apparent enhancement changes. The 95.2% (20/21) of lesions with heterogeneous enhancement on the first contrast-enhanced sequence correlated with type B or type C pathologic findings, whereas 4.8% (1/21) with homogeneous enhancement correlated with type A pathologic findings. Among the 20 type B or type C lesions, 80% (16/20) achieved total or near-total resection.
CONCLUSION
Progressive contrast "filling in" in the tumors on conventional contrast-enhanced MR images can aid in differentiating between cavernous sinus lesions and suggest the diagnosis of cavernous hemangiomas. | 10.3174/ajnr.A0845 |
pubmed_215_16534 | BACKGROUND & AIMS
Animal studies have shown that more than half of the dietary protein intake is used by the gut and that a large proportion of this utilization is devoted to (glyco-)protein synthesis. Recycling of these secretions may play a critical role in the regulation of overall dietary amino acid bioavailability.
METHODS
Four piglets (age 32 days, 8-10 kg) bearing portal, arterial, and duodenal catheters and a portal flow probe were infused with a complete diet via the duodenum for 12 hours, followed by 12 hours of fasting. The portal balance of glucose and amino acids was measured throughout the 24-hour period. The animals also received duodenal and intravenous infusions of different lysine and threonine tracers. Measurements of intestinal tracer utilization and reappearance in the portal blood were used to calculate intestinal amino acid utilization and recycling.
RESULTS
From 0 to 6 hours, one third of the protein intake appeared in the portal blood. As feeding continued, the portal glucose balance (60% of intake) was constant, but the net amino acid portal balance became progressively more positive. Significant net amino acid absorption continued for at least 6 hours after the cessation of feeding. Over 24 hours, 52% of the dietary protein intake appeared in the circulation and one third of this derived from recycled intestinal secretions.
CONCLUSIONS
Intestinal recycling of amino acids contributes significantly to their systemic availability and may be a critical factor in amino acid nutrition. | 10.1053/gast.2002.37062 |
pubmed_504_9276 | The detection and identification of road anomalies and obstacles in the road infrastructure has been investigated by the research community using different types of sensors. This paper evaluates the detection and identification of road anomalies/obstacles using the data collected from the Inertial Measurement Unit (IMU) installed in a vehicle and in particular from the data generated by the accelerometers' and gyroscopes' components. Inspired by the successes of the application of deep learning to various identification problems, this paper investigates the application of Convolutional Neural Network (CNN) to this specific problem. In particular, we propose a novel approach in this context where the time-frequency representation (i.e., spectrogram) is used as an input to the CNN rather than the original time domain data. This approach is evaluated on an experimental dataset collected using 12 different vehicles driving for more than 40 km of road. The results show that the proposed approach outperforms significantly and across different sampling rates both the application of CNN to the original time domain representation and the application of shallow machine learning algorithms. The approach achieves an identification accuracy of 97.2%. The results presented in this paper are based on an extensive optimization both of the CNN algorithm and the spectrogram implementation in terms of window size, type of window, and overlapping ratio. The accurate detection of road anomalies/obstacles could be useful to road infrastructure managers to monitor the quality of the road surface and to improve the accurate positioning of autonomous vehicles because road anomalies/obstacles could be used as landmarks. | 10.3390/s20226425 |
pubmed_672_11424 | During a 10-year period between 1978 and 1987, there were 25 confirmed cases of herpes esophagitis with positive esophageal brushings, biopsies, and/or cultures for the herpes simplex virus. Eighteen of those patients had double-contrast esophagrams, but two were excluded from our study because they had combined fungal and viral esophagitis. All of the remaining 16 patients were symptomatic, and 14 were immunocompromised. Herpes esophagitis was diagnosed on the original radiographic reports in nine (56%) of those 16 patients. In all nine, double-contrast radiographs revealed discrete, superficial ulcers on a relatively normal background mucosa without significant plaque formation. In the remaining seven patients, double-contrast esophagrams revealed plaquelike lesions that were indistinguishable from those of Candida esophagitis (four cases), thickened folds (two cases), and a giant esophageal ulcer (one case). During the same period, herpes esophagitis was diagnosed on seven other double-contrast esophagrams in which histologic, cytologic, and virologic studies were negative for the herpes simplex virus. However, the endoscopic findings were also suspicious for herpes esophagitis in six of those cases, suggesting that they may represent true-positive cases in which there was inadequate tissue sampling. Thus, our experience indicates that radiographic abnormalities can almost always be detected on double-contrast esophagrams in patients with herpes esophagitis, and in more than 50% of cases, a specific radiographic diagnosis can be made because of discrete ulcers without significant plaque formation. | 10.2214/ajr.151.1.57 |
pubmed_1121_3795 | BACKGROUND
Although accumulating evidence suggests a more extensive reduction of low-density lipoprotein cholesterol (LDL-C), it is unclear whether a higher statin dose is more effective and cost-effective in the Asian population. This study compared the efficacy, safety, and cost-effectiveness of atorvastatin 20 and 10 mg in high-risk Asian patients with hypercholesterolemia.
METHODS
A 12-week, open-label, parallel, multicenter, Phase IV randomized controlled trial was conducted at ten hospitals in the Republic of Korea between October 2017 and May 2019. High-risk patients with hypercholesterolemia, defined according to 2015 Korean guidelines for dyslipidemia management, were eligible to participate. We randomly assigned 250 patients at risk of atherosclerotic cardiovascular disease to receive 20 mg (n = 124) or 10 mg (n = 126) of atorvastatin. The primary endpoint was the difference in the mean percentage change in LDL-C levels from baseline after 12 weeks. Cost-effectiveness was measured as an exploratory endpoint.
RESULTS
LDL-C levels were reduced more significantly by atorvastatin 20 mg than by 10 mg after 12 weeks (42.4% vs. 33.5%, p < 0.0001). Significantly more patients achieved target LDL-C levels (<100 mg/dL for high-risk patients, <70 mg/dL for very high-risk patients) with atorvastatin 20 mg than with 10 mg (40.3% vs. 25.6%, p < 0.05). Apolipoprotein B decreased significantly with atorvastatin 20mg versus 10 mg (-36.2% vs. -29.9%, p < 0.05). Lipid ratios also showed greater improvement with atorvastatin 20 mg than with 10 mg (total cholesterol/high-density lipoprotein cholesterol ratio, -33.3% vs. -29.4%, p < 0.05; apolipoprotein B/apolipoprotein A1 ratio, -36.7% vs. -31.4%, p < 0.05). Atorvastatin 20 mg was more cost-effective than atorvastatin 10 mg in terms of both the average and incremental cost-effectiveness ratios. Safety and tolerability of atorvastatin 20 mg were comparable to those of atorvastatin 10 mg.
CONCLUSION
In high-risk Asian patients with hypercholesterolemia, atorvastatin 20 mg was both efficacious in reducing LDL-C and cost-effective compared with atorvastatin 10 mg. | 10.1371/journal.pone.0245481 |
pubmed_17_2879 | T-lymphocyte subsets were studied in two patient groups: (1) 50 patients with homozygous sickle cell anaemia (SCA) (mean age 12 (range 3-32) years old) in good health at the time of the study who showed no infectious complication. (2) 50 patients (mean age 13 (range 4-29) years old) with normal haemoglobin rate. The global response revealed a significant increase in levels of CD3+ (P=0.04) and CD8+ (P=0.04) cells when compared with the control group, there was no significant difference in levels of CD4+ cells (P=0.05) between the two groups. However, there was a relationship between T-cell subpopulation levels and spleen status. The average values of T-cell subsets (CD4+ and CD8+) in patients with SCA-induced splenic defects (asplenic, splenomegaly or splenectomized patients) were significantly reduced when compared to SCA patients with normal spleens and the control groups. These data show that T-cell activity was reduced in patients with splenic defects. A correlation between splenic status and a perturbed host defence system in patients with SCA suggests that monitoring T-cell subsets might have prognostic value in the course of sickle cell disease. | 10.1038/sj.thj.6200310 |
pubmed_528_23377 | The interferon-alpha (IFN-alpha) gene family is an important part of the immune system. Recombinant interferon-alpha is widely used to treat viral hepatitis and malignant diseases. Marmota himalayana has been found to be susceptible to woodchuck hepatitis virus, a virus genetically related to hepatitis B virus (HBV), and is suitable as an animal model for studies on HBV infection. Here, the IFN-alpha gene family of M. himalayana (cwIFN-alpha) was characterized. Sequence data indicate that the cwIFN-alpha family consists of at least 8 functional sequences and 6 pseudogenes with high homology within the family and to IFN-alpha of Marmota monax, a related species and well-established animal model. The recombinant cwIFN-alpha subtypes were expressed and tested to be active in viral protection assay and to induce expression of MxA in a species-specific manner. This work provides essential information for future work on testing new therapeutic approaches of HBV infection based on IFN-alpha in M. himalayana. | 10.1016/j.dci.2007.08.003 |
pubmed_129_7027 | The Authors have tested the new Tb-Elisa method to detect specific antibodies, raised against A60 major mycobacterial antigen complex, in patients of groups II, III and IV of CDC classification suffering from acquired immunodeficiency and in HIV-1 negative control subjects. The test results support laboratory diagnosis of acute phase and reactivation of mycobacterial infection. | pubmed_129_7027 |
pubmed_458_16300 | OBJECTIVE
To study the effect of mycophenolate mofetil therapy on the pharmacokinetic parameters of a number of antiretroviral drugs, on intracellular pools of deoxycytidine triphosphate (dCTP) and deoxyguanosine triphosphate (dGTP), and on intracellular concentrations of the triphosphate of lamivudine (3TCTP).
DESIGN
Randomised pharmacokinetic study.
PARTICIPANTS
Nineteen HIV-1-infected patients.
METHODS
Antiretroviral-naive men starting treatment with didanosine 400 mg once daily, lamivudine 150 mg twice daily, abacavir 300 mg twice daily, indinavir 800 mg twice daily, ritonavir 100 mg twice daily and nevirapine 200 mg twice daily were randomised to a group with or without mycophenolate mofetil 500 mg twice daily. After 8 weeks of therapy, the plasma pharmacokinetic profiles of mycophenolic acid (the active metabolite of mycophenolate mofetil), abacavir, indinavir and nevirapine, and triphosphate concentrations (dCTP, dGTP and 3TCTP) in peripheral blood mononuclear cells, were determined.
RESULTS
Nine of the 19 patients received mycophenolate mofetil. There was no difference in plasma clearance of indinavir or abacavir between the two groups. The clearance of nevirapine was higher in patients using mycophenolate mofetil (p = 0.04). In 12 patients, of whom five also received mycophenolate mofetil, intracellular triphosphates were measured. There was no significant difference in intracellular dCTP, dGTP or 3TCTP concentrations between the two groups.
CONCLUSION
In this small cohort of patients, mycophenolate mofetil therapy reduced the plasma concentration of nevirapine but had no effect on plasma concentrations of indinavir and abacavir. There were no consistent effects of mycophenolic acid on the intracellular concentrations of dCTP, dGTP or 3TCTP. | 10.2165/00003088-200443120-00004 |
pubmed_251_10217 | Deafferentation syndromes have in common the existence of a physical injury and/or of a functional impairment of a nerve, either somatosensory afferent (Phantom Limb Pain) and/or sympathetic efferent (Reflex Sympathetic Dystrophy). These progressively debilitating syndromes are the witness of the absence of self-limitation of neuronal sensitization, which is normally the evolution of any painful stimulation of spinal cord neurons. To some extent deafferentation syndromes could be defined as a maladaptive neuronal plasticity. The lack of complete understanding of underlying pathophysiological mechanisms gives account of the wide variety of proposed treatments and of their unpredictable and variable efficacy. This fact is also due in part to the lack of controlled studies of most of the therapeutic propositions, whose purported efficacy is usually based on anecdotal reports. Finally, the role of prevention must be strongly emphasized, focusing, if those syndromes are likely to occur following surgery, on the importance of pre- and postoperative efficient analgesia, and also, possibly, on the preemptive role of regional anaesthetic techniques. | pubmed_251_10217 |
pubmed_192_6296 | Objective
To explore the feasibility of posterior debridement, decompression, bone grafting, and fixation in treatment of thoracic spinal tuberculosis with myelopathy, and investigate the effects of surgical timing on postoperative outcomes.
Methods
The clinical data of 26 patients with thoracic spinal tuberculosis with myelopathy between August 2012 and October 2015 was retrospectively analyzed. All patients underwent posterior unilateral transpedicular debridement, decompression, bone grafting, and fixation and were divided into two groups according to surgical timing. Group A included 11 patients with neurological dysfunction lasting less than 3 months; group B included 15 patients with neurological dysfunction lasting more than 3 months. No significant difference was found between the two groups in gender, age, involved segments, preoperative erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Cobb angle of involved segment, and preoperative American Spinal Injury Association (ASIA) classification ( P>0.05). The operation time, intraoperative blood loss, hospitalization stay, perioperative complications, and bone fusion time were recorded and compared between the two groups. The change of pre- and post-operative Cobb angle of involved segments was calculated. Neurological function was assessed according to ASIA classification.
Results
All patients were followed up 25-60 months (mean, 41.6 months). No cerebrospinal fluid leakage occurred intra- and post-operation. The hospitalization stay and perioperative complications in group A were significantly less than those of group B ( P<0.05). There was no significant difference in operation time, intraoperative blood loss, and bone fusion time between the two groups ( P>0.05). At last follow-up, there was no significant difference in ESR and CRP between groups A and B ( P>0.05), but they were all significantly lower than those before operation ( P<0.05). In group A, 1 patient with T 6, 7 tuberculosis developed sinus that healed after dressing; the implants were removed at 20 months with bony union and no recurrence was found after 36 months of follow-up. One patient with T 4, 5 tuberculosis in group B underwent revision because of recurrence and distal junctional kyphosis of the thoracic spine at 26 months after operation. There was no internal fixation-related complications or tuberculosis recurrence occurred in the remaining patients. At last follow-up, the Cobb angles in the two groups significantly improved compared with those before operation ( P<0.05), but there was no significant difference in the Cobb angle and correction degree between the two groups ( P>0.05). At last follow-up, the ASIA classification of spinal cord function was grade C in 1 case and grade E in 10 cases in group A, and grade D in 2 cases and grade E in 13 cases in group B; the ASIA classification results in the two groups significantly improved compared with preoperative ones ( P<0.05), but no significant difference was found between the two groups ( Z=-0.234, P=1.000).
Conclusion
Posterior unilateral transpedicular debridement, decompression, bone grafting, and fixation is effective in treatment of thoracic spinal tuberculosis with myelopathy. Early surgery can reduce the hospitalization stays and incidence of perioperative complications. | 10.7507/1002-1892.201808071 |
pubmed_881_22919 | There is an early rise in secretion of luteinizing hormone (LH) in bull calves between 6 and 20 weeks of age. This study was designed to examine the involvement of opioidergic and dopaminergic neuronal systems in the control of this early rise in gonadotrophin secretion. Four groups of five bull calves were bled every 15 min for 10 h and administered one of the following treatments i.v. at 6, 14 and 24 weeks of age: a) saline; b) 1 mg naloxone/kg body weight every hour for 10 h; c) 0.8 mg pimozide/kg body weight as a single injection, after the first blood sample; d) 1 mg naloxone + 0.8 mg Pimozide/kg body weight. The early rise in LH secretion had started by 6 weeks of age, was at a peak at 14 weeks of age and was complete by 24 weeks of age (P<0.05). Naloxone (an opioid antagonist) treatment resulted in increased basal and mean serum concentrations of LH and LH pulse frequency at 14 weeks of age, increased mean serum LH concentrations of LH pulse frequency at 24 weeks of age, decreased FSH pulse amplitude at 14 weeks of age and increased mean serum concentrations of FSH at 24 weeks of age compared to control calves (P<0.05). Pimozide (a dopamine antagonist) decreased LH pulse amplitude at 24 weeks of age compared to all other groups of calves (P<0.05). Naloxone and pimozide in combination resulted in LH secretory patterns similar to naloxone treated calves or intermediate to naloxone and control calves at 14 weeks of age but similar to control calves at 24 weeks of age. In calves given the combination treatment, parameters of FSH secretion resembled those in the other groups of calves except for basal and mean serum concentrations of FSH at 24 weeks of age, which were similar to control or pimozide treated calves, but lower than in naloxone treated calves (P<0.05). At 14 weeks of age mean serum concentrations of testosterone were greater in calves given naloxone and pimozide in combination compared to controls, but at 24 weeks of age they were greater in the naloxone treated calves and lower in pimozide treated calves compared to the control calves (P<0.05). We concluded that an opioidergic inhibition of LH secretion was seen from the middle of the early rise in LH secretion (14 weeks of age) onwards but inhibition of FSH secretion was only seen at 24 weeks of age. A dopaminergic drive for LH and FSH secretion developed after the completion of the early rise in gonadotrophin secretion (24 weeks of age). Opioidergic inhibition of gonadotrophin secretion largely involved inhibition of a dopaminergic drive at the end of the early rise in LH secretion (24 weeks of age) but not at earlier ages. | 10.1046/j.1365-2826.1997.00306.x |
pubmed_262_2237 | Deeper semantic processing of words leads to enhanced memory encoding (depth of processing effect). The left inferior prefrontal cortex (LIPC) and the left hippocampus are known to be involved in this effect. We tested the hypothesis that different semantic encoding processes contribute qualitatively differently to memory encoding. In a memory experiment using functional magnetic resonance imaging, we compared three different encoding tasks: a nonsemantic alphabetical, an animacy decision, and a size comparison tasks. Recognition memory was tested subsequently. We hypothesized that the size comparison task would activate brain areas involved in the processing of object features and that this would be associated with successful memory encoding. Results showed that the size comparison task led to significantly better memory encoding than the two other tasks. As with the animacy decision task, it led to stronger activation of the LIPC and left hippocampus than the nonsemantic task. Both regions also had stronger activations for later remembered than for nonremembered words. The size comparison task additionally led to stronger activation in the left anterior fusiform gyrus, which was also associated with successful memory encoding. We conclude that different types of semantic processing affect memory encoding based on distinguishable brain processes. | 10.1002/hbm.20969 |
pubmed_923_5642 | To evaluate the usefulness of assessing bone components using magnetic resonance imaging (MRI), the contributions of bone components, including mineral, fat and collagen, to bone mineral density (BMD) and T1 relaxation time (T1) were studied using phantoms. Excised human vertebrae were also evaluated by quantitative computed tomography (QCT) and MRI. T1 was shortened with increasing quantities of fat and collagen. In water, T1 was significantly affected by bone density, while in oil, T1 became slightly longer as bone density increased. The presence of fat and collagen caused under- and overestimations of BMD, respectively. There was good correlation between T1 and BMD in osteoporotic vertebrae and the vertebrae with long T1 showed an increased content of hematopoietic marrow and/or abnormally increased bone mineral. It was concluded that the experimental data showed that MRI can contribute to the assessment of bone quality. | 10.1007/BF00197987 |
pubmed_663_9441 | A novel heterotrophic, marine, strictly aerobic, motile bacterium was isolated from the Red Sea at a depth of 1 m. Analysis of its 16S rRNA gene sequence, retrieved from the whole-genome sequence, showed that this bacterium was most closely related to the genera Oleispira, Oceanobacter and Thalassolituus, each of which contains a single species, within the class Gammaproteobacteria. Phenotypic, genotypic and phylogenetic analyses supported the creation of a novel genus and species to accommodate this bacterium, for which the name Bermanella marisrubri gen. nov., sp. nov. is proposed. The type strain of Bermanella marisrubri is RED65(T) (=CECT 7074(T) =CCUG 52064(T)). | 10.1099/ijs.0.002113-0 |
pubmed_181_7101 | Ceramics are materials of choice for hip joint implants because of their excellent biocompatibility and mechanical properties. Wear of the bearing couple (femoral head and cup) remains one of the main concerns of hip implants. Although ceramics are known for their good tribological properties, shocks due to micro-separation, friction and hydrothermal ageing in physiological environment remain the three main sources of wear. It has been recently suggested that shock effects dominate but the three degradation mechanisms were so far simulated separately. We developed a procedure that combines sequences of shocks, hydrothermal ageing in an autoclave and friction on hip-walking simulator to investigate their combined effects on Zirconia Toughened Alumina (ZTA) implants. Our results confirm that shocks can be considered as the key phenomenon causing wear, and that their effect is independent of friction and hydrothermal degradation. The analysis of retrieved femoral heads reveals wear features comparable to the ones created experimentally by shocks. Standards (ASTM or ISO) could be improved by including shock tests, which are more relevant than wear tests currently performed on hip simulators at least for Ceramic-on- Ceramic couplings. | 10.1016/j.jmbbm.2016.09.019 |
pubmed_55_9512 | PURPOSE
Extranodal natural killer (NK)/T-cell lymphoma is a rare neoplasm and limited data has reported regarding the utilization of fluorine-18, fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) in this disease. The aim of this study was to assess the role of F-FDG PET/CT in the staging of NK/T-cell lymphomas.
PATIENTS AND METHODS
Thirteen newly diagnosed and two recurrent patients with NK/T-cell lymphoma who received F-FDG PET/CT were studied. The lesion with intense F-FDG uptake was suggested as the positive and was measured using maximal standardized uptake values. The results of PET/CT were compared with the conventional staging examinations.
RESULTS
F-FDG PET/CT detected nasal or extranasal lymphoma lesions in at least one site in all of the 15 patients. There was no significant difference of F-FDG uptake in lesions between patients with stage I-II disease and those with stage III-IV disease (maximal standardized uptake values 8.44+/-5.56 vs. 10.32+/-7.80; t=0.757, P>0.05). In two patients with an indeterminate diagnosis, the diagnosis of NK/T-cell lymphomas was established by biopsy guided by PET/CT and the status of stage IV was correctly identified. In 13 patients with definite diagnosis, the stage of disease was changed in six patients on the basis of F-FDG PET/CT. Two patients were down staged, and four patients upstaged.
CONCLUSION
The lesions of the NK/T-cell lymphoma are F-FDG avid and PET/CT seems to be useful in the staging of this disease. | 10.1097/MNM.0b013e32833310fa |
pubmed_112_5913 | A two-part survey was conducted on psychiatrists' contact with the families of patients who have committed suicide. Families of suicide victims were surveyed to see if they had been contacted and whether they wished to be contacted. In one of the 12 cases, the psychiatrist initiated a contact, and in 11 of the 12 cases, the families wished they had been contacted. Reasons for the discrepancy between what the psychiatrists did and what the families wanted are discussed. | 10.1177/070674379203700312 |
pubmed_721_9201 | The results are presented of palliative telecobaltotherapy in patients with metastases to the brain. The patients received a dose of 30 Gy in 10 fractions during 2 weeks. Clinical improvement was achieved in 28 out of 33 treated patients (85%). The survival time after the completion of radiotherapy was from 1 to 15 months, mean 5 months. | pubmed_721_9201 |
pubmed_399_9034 | The posterior interosseous syndrome appears in two forms, a) paralytical, and b) painful. In this investigation the authors report on twelve operated patients with painful posterior interosseous or "radial tunnel" syndrome. The intraoperative findings in the arcade of Frohse are compared with the findings on preparation of ten recently deceased. It was especially significant that in ten of twelve cases there was found intraoperatively a tendinous type of arcade. In the cadaveric studies the authors encountered this type of tendinous arcade in only two of ten specimens. Based on these findings, the authors conclude that the tendinous arcade of Frohse is an important factor in the development of the posterior interosseous syndrome. | pubmed_399_9034 |
pubmed_975_7970 | Cyclosporine recently has become part of the treatment regimen for patients with refractory inflammatory bowel disease, though it is still considered investigational for that purpose. However, little attention has been given to the potential hepatotoxicity associated with cyclosporine administration. This can be especially significant in patients with preexisting abnormalities of liver function, including those induced by total parenteral nutrition. | 10.1097/00007611-199508000-00010 |
pubmed_761_2346 | A new multivariate standard addition strategy applicable to stripping methods was proposed as an extention of the classical univariate standard addition method for the resolution of complex samples involving overlapped peaks and complex matrices. The proposed strategy consists in alternate additions of the considered analytes and the further extrapolation to a simulated blank solution measured by skipping the preconcentration step (deposition time = 0). This calibration approach was successfully tested in tonic water samples spiked with Tl(I) and In(III) using a sensor array based on a SeCyst-SPCNFE and an ex-situ-BiSPCE, providing good concordance between replicates and much better accuracy than the usual multivariate external calibration method. | 10.1016/j.talanta.2018.09.035 |
pubmed_1028_6480 | Cranial CT in 39 patients (23 belonged to 8 families) with four different groups of hereditary ataxia (HA) showed mainly three combinations of atrophic findings: (1) cerebellar ataxia (CA, n = 17) had marked atrophy of the cerebellum and/or the brain stem combined with moderate cerebral atrophy; (2) an intermediate group consisting of hereditary spastic paraplegia (HSP, n = 10) and Friedreich's ataxia (FA, n = 7), both with moderate infra- and supratentorial atrophy; (3) atrophy was hardly demonstrated in the group of Charcot-Marie-Tooth disease (CMT, n = 5). HA cases with atrophy could be distinguished from multiple sclerosis (MS) by CT. | 10.1007/BF00395291 |
pubmed_836_7852 | This study was conducted to determine whether or not exogenous gonadotropin releasing hormone (GnRH) alters the timing or improves the synchrony of estrus, the LH surge, and ovulation following estrous synchronization in dwarf goats, and to assess the effects of season on these parameters. In January and June, estrus was synchronized in 12 Pygmy and Nigerian Dwarf goats with a 10-day progestagen sponge, 125 microg cloprostenol i.m. 48 h before sponge removal, and 300 IU equine chorionic gonadotrophin (eCG) i.m. at sponge removal. Six of the 12 goats were given 50 microg GnRH i.m. 24h after sponge removal. Onset of estrus was monitored using two males. Samples for plasma LH were collected at 2 h intervals beginning 22 h after sponge removal and ending at 48 h in January and at 58 h in June. Time of ovulation time was confirmed by laparoscopy at 36, 50, 60, and 74 h in January and at 50, 60, and 74 h in June. Administration of GnRH had no significant effect on the onset of estrus; however, it reduced the interval from sponge removal to the LH surge and improved the synchrony of the LH surge (P<0.05). Treatment with GnRH also reduced the interval from sponge removal to ovulation and improved the synchrony of ovulation (P<0.05). Season had a significant effect on the timing and the synchrony of estrus with and without GnRH treatment (P<0.05). A seasonal shift was also observed in the timing of the LH surge in the absence of GnRH treatment (P<0.05). Further research is required to determine the optimum time for GnRH administration and the minimum effective dose in dwarf goats. | 10.1016/s0093-691x(03)00037-2 |
pubmed_199_4441 | The development of systemic humoral and cellular immunity following antigen presentation in the inner ear was compared with that seen following middle ear and peritoneal inoculation routes. Antibody developing against keyhole limpet hemocyanin was measured by a sensitive enzyme-linked immunofiltration assay, and cell-mediated immunity was measured by in vitro lymphocyte blastogenesis. The inner ear and peritoneal routes of antigen presentation resulted in a parallel rise in antibody over a 3-week period. In contrast, the middle ear route resulted in a weak, transient antibody response by 2 weeks. The acquisition of cell-mediated immunity occurred earliest (day 14) in the group receiving antigen intraperitoneally. A significant but smaller proliferative response was also seen in the group receiving antigen via the inner ear route on days 14 and 21. In contrast, the middle ear route failed to result in cell-mediated immunity. These studies indicate that the inner ear is an effective route of antigen processing which results in the acquisition of systemic humoral and cellular immunity. The development of systemic immunity, in turn, has been found to be protective of the inner ear. | 10.1016/s0196-0709(85)80077-6 |
pubmed_707_18162 | BACKGROUND
Edema is one of the cardinal clinical features of nephrotic syndrome (NS). It may vary from mild periorbital edema to severe generalized edema (anasarca). In patients where edema does not improve with prednisone therapy, the most common supportive medications are diuretics and albumin. However, due to the complex pathophysiology of edema formation in NS patients resulting in intravascular normovolemia or hypovolemia, optimal therapy for edema is still debated. We conducted a systematic review with the objective of evaluating the change in urine volume and urine sodium excretion after treatment with furosemide only versus furosemide with albumin in edematous patients with NS.
OBJECTIVES
(1) To evaluate efficacy of furosemide alone versus furosemide with albumin in the treatment of nephrotic edema in adults and children. (2) To compare the harms and benefits of different doses of furosemide for treating nephrotic edema.
SEARCH METHODS
The search included all randomized or quasi-randomized controlled trials in English and French using MEDLINE, Embase, and CENTRAL Trials Registry of the Cochrane Collaboration using the Ovid interface.
CLINICALTRIALS
gov and the International Clinical Trials Registry Platform were also searched.
SELECTION CRITERIA
We included all RCTs and randomized cross-over studies in which furosemide and furosemide plus albumin are used in the treatment of children or adults with nephrotic edema. We excluded patients with hypoalbuminemia of non-renal origin and severe chronic kidney disease (CKD) with a glomerular filtration rate below 30 ml/min/1.74 m2 and patients with congenital NS.
DATA COLLECTION AND ANALYSIS
All abstracts were independently assessed by at least two authors to determine which studies met the inclusion criteria. Information on study design, methodology, and outcome data (urine volume, urine sodium excretion, adverse effects) from each identified study was entered into a separate data sheet. The differences in outcomes between the types of therapy were expressed as standardized mean difference (SMD) with 95% confidence intervals (CI).
RESULTS
The search yielded 525 records, and after screening, five studies were included in the systematic review and four of those studies in the meta-analysis. One study had high risk of bias and the remaining three studies were deemed to have some concerns. Urine excretion was greater after treatment with furosemide and albumin versus furosemide (SMD 0.85, 95% CI = 0.33 to 1.38). Results for sodium excretion were inconclusive (SMD 0.37, 95%CI = - 0.28 to 1.02).
AUTHORS' CONCLUSIONS
The current evidence is not sufficient to make definitive conclusions about the role of albumin in treating nephrotic edema. High-quality randomized studies with adequate samples sizes are needed. Including an assessment of intravascular volume status may be helpful.
TRIAL REGISTRATION
Prospero: CRD4201808979. https://www.crd.york.ac.uk/PROSPERO A higher resolution version of the Graphical abstract is available as Supplementary information. | 10.1007/s00467-021-05358-4 |
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