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pubmed_428_20186
Recent experimental advances are producing an avalanche of data on both neural connectivity and neural activity. To take full advantage of these two emerging datasets we need a framework that links them, revealing how collective neural activity arises from the structure of neural connectivity and intrinsic neural dynamics. This problem of structure-driven activity has drawn major interest in computational neuroscience. Existing methods for relating activity and architecture in spiking networks rely on linearizing activity around a central operating point and thus fail to capture the nonlinear responses of individual neurons that are the hallmark of neural information processing. Here, we overcome this limitation and present a new relationship between connectivity and activity in networks of nonlinear spiking neurons by developing a diagrammatic fluctuation expansion based on statistical field theory. We explicitly show how recurrent network structure produces pairwise and higher-order correlated activity, and how nonlinearities impact the networks' spiking activity. Our findings open new avenues to investigating how single-neuron nonlinearities-including those of different cell types-combine with connectivity to shape population activity and function.
10.1371/journal.pcbi.1005583
pubmed_383_15775
The SARS-CoV-2 virus causes severe acute respiratory syndrome (COVID-19) and has rapidly created a global pandemic. Patients that survive may face a slow recovery with long lasting side effects that can afflict different organs. SARS-CoV-2 primarily infects epithelial airway cells that express the host entry receptor Angiotensin Converting Enzyme 2 (ACE2) which binds to spike protein trimers on the surface of SARS-CoV-2 virions. However, SARS-CoV-2 can spread to other tissues even though they are negative for ACE2. To gain insight into the molecular constituents that might influence SARS-CoV-2 tropism, we determined which additional host factors engage with the viral spike protein in disease-relevant human bronchial epithelial cells (16HBEo - ). We found that spike recruited the extracellular proteins laminin and thrombospondin and was retained in the endoplasmatic reticulum (ER) by the proteins DJB11 and FBX2 which support re-folding or degradation of nascent proteins in the ER. Because emerging mutations of the spike protein potentially impact the virus tropism, we compared the interactome of D614 spike with that of the rapidly spreading G614 mutated spike. More D614 than G614 spike associated with the proteins UGGT1, calnexin, HSP7A and GRP78/BiP which ensure glycosylation and folding of proteins in the ER. In contrast to G614 spike, D614 spike was endoproteolytically cleaved, and the N-terminal S1 domain was degraded in the ER even though C-terminal 'S2 only' proteoforms remained present. D614 spike also bound more laminin than G614 spike, which suggested that extracellular laminins may function as co-factor for an alternative, 'S2 only' dependent virus entry. Because the host interactome determines whether an infection is productive, we developed a novel proteome-based cell type set enrichment analysis (pCtSEA). With pCtSEA we determined that the host interactome of the spike protein may extend the tropism of SARS-CoV-2 beyond mucous epithelia to several different cell types, including macrophages and epithelial cells in the nephron. An 'S2 only' dependent, alternative infection of additional cell types with SARS-CoV-2 may impact vaccination strategies and may provide a molecular explanation for a severe or prolonged progression of disease in select COVID-19 patients.
10.1101/2021.02.16.431318
pubmed_437_23083
OBJECTIVES The definition of hypertension in children is too complex to be used by medical professionals and children and their parents because of the age-, gender-, and height-specific blood pressure (BP) algorithm. The aim of this study was to simplify the pediatric BP percentile references using BP to height ratio (BPHR, equal to BP/height) for screening for prehypertension and hypertension in Chinese children. METHODS Data were obtained from the China Health and Nutrition Survey, which was conducted from 1991 to 2009 and included 11 661 children aged 6 to 17 years with complete data on age, gender, height, and BP values. Receiver operating characteristic curve analysis was performed to assess the performance of systolic BPHR (SBPHR) and diastolic BPHR (DBPHR) for screening for pediatric prehypertension and hypertension. RESULTS The optimal thresholds for defining prehypertension were 0.81 in children aged 6 to 11 years and 0.70 in adolescents aged 12 to 17 years for SBPHR and 0.52 in children and 0.46 in adolescents for DBPHR, respectively. The corresponding values for hypertension were 0.84, 0.78, 0.55, and 0.50, respectively. The negative predictive values were much higher (all ≥99%) for prehypertension and hypertension, although the positive predictive values were relatively lower, ranging from 13% to 75%. CONCLUSIONS BPHR index is simple and accurate for screening for prehypertension and hypertension in Chinese children aged 6 to 17 years and can be used for early screening or treating Chinese children with hypertension.
10.1542/peds.2014-0643
pubmed_1005_13178
A bacterial strain, designated 39S1MBT, isolated from a root nodule of a soybean plant that had been inoculated with root-zone soil of Amphicarpaea bracteata (hog peanut) growing in Canada, was previously characterized and placed in a novel lineage within the genus Bradyrhizobium. The taxonomic status of strain 39S1MBT was verified by genomic and phenotypic analyses. Phylogenetic analyses of individual and concatenated protein-encoding gene sequences (atpD, glnII, recA, gyrB and rpoB) placed 39S1MBT in a lineage distinct from named species. Data for sequence similarities of concatenated genes relative to type strains of named species supported the phylogenetic data. Average nucleotide identity values of genome sequences (84.5-91.7 %) were well below the threshold value for bacterial species circumscription. Based on these data, Bradyrhizobium ottawaense OO99T and Bradyrhizobium shewense ERR11T are close relatives of 39S1MBT. The complete genome of 39S1MBT consists of a single 7.04 Mbp chromosome without a symbiosis island; G+C content is 64.7 mol%. Present in the genome are key photosystem and nitrogen-fixation genes, but not nodulation and type III secretion system genes. Sequence analysis of the nitrogen fixation gene, nifH, placed 39S1MBT in a novel lineage distinct from named Bradyrhizobium species. Data for phenotypic tests including growth characteristics and carbon source utilization supported the sequence-based analyses. Based on the data presented here, a novel species with the name Bradyrhizobium amphicarpaeae sp. nov. is proposed with 39S1MBT (=LMG 29934T=HAMBI 3680T) as the type strain.
10.1099/ijsem.0.003569
pubmed_343_17424
Ergot alkaloids are vasoconstrictors frequently detected in low concentrations in livestock feed. The Canadian Food Inspection Agency permits up to 3,000 μg ergot alkaloids per kg cattle feed. The objective of this study was to examine the effects of feeding low concentrations of ergot alkaloids over 9-weeks on vascular dynamics in the caudal and internal iliac arteries of beef cows. A relationship between ergot alkaloid concentration in feed and hemodynamic changes in the caudal and internal iliac arteries was hypothesized. Periparturient beef cows were randomized into four groups and group fed mixed rations containing <15 μg ergot alkaloids per kg of dry matter intake (Control, n = 9), 48 μg/kg (Low, n = 9), 201 μg/kg (Medium, n = 8), and 822 μg/kg (High, n = 6). Three experimental periods comprised the study: pre-treatment (2 weeks), treatment (9 weeks), and post-treatment (3 weeks). B-mode and Doppler ultrasonography was performed weekly to measure hemodynamic endpoints. Plasma prolactin concentrations and rectal temperatures were measured weekly. Caudal artery diameter decreased (Treatment*Experimental Period i.e., Tx*EP, p < 0.001) by 14% in the High group during the treatment period. Reductions (Tx*EP, p < 0.001) in caudal artery blood flow (37%, 29%) and blood volume per pulse (29%, 11%) were recorded during the treatment period in the High and Medium groups. Internal iliac artery diameter and blood flow decreased (Tx*EP, p ≤ 0.004) by 13% and 40% during the treatment period in the Medium group. Moderate reductions (Tx*EP, p ≤ 0.042; 12-25%) in the mean blood velocity during the treatment and post-treatment periods and decreases (Tx*EP, p ≤ 0.01; 12-17%) in the peak systolic velocity of both arteries during the post-treatment period were also detected. Prolactin did not change in any group during the treatment period (p = 0.462). Rectal temperatures were within the normal physiological range for beef cows. In conclusion, we documented moderate vasoconstriction in the caudal artery and the internal iliac artery in cows fed 201-822 μg ergot alkaloids per kg of dry matter intake for 9-week period near parturition. The pattern of alterations was similar between the caudal and internal iliac arteries. Results of this study suggest that feeding up to 822 μg/kg produce reversible pharmacological changes in beef cow vasculature and warrant reconsideration of current regulations for cattle.
10.3389/fvets.2019.00262
pubmed_992_25564
BACKGROUND Few studies have quantified cardiorespiratory fitness among individuals seeking bariatric surgery. Treadmill testing allows researchers to determine exercise capacity through metabolic equivalents. These findings can assist clinicians in understanding patients' capabilities to carry out various activities of daily living. The purpose of this study was to determine exercise tolerance and the variables associated with fitness, among individuals seeking bariatric surgery. METHODS Bariatric surgery candidates completed submaximal treadmill testing and provided ratings of perceived exertion. Each participant also completed questionnaires related to history of exercise, mood, and perceived barriers/benefits of exercise. RESULTS Over half of participants reported that exercise was "hard to very hard" before reaching 70% of heart rate reserve, and one-third of participants reported that exercise was "moderately hard" at less than 3 metabolic equivalents (light activity). Body mass index and age accounted for the majority of the variance in exercise tolerance, but athletic history, employment status, and perceived health benefits also contributed. Perceived benefit scores were higher than barrier scores. CONCLUSION Categories commonly used to describe moderate-intensity exercise (3-6 metabolic equivalents) do not coincide with perceptions of intensity among many bariatric surgery candidates, especially those with a body mass index of 50 or more.
10.1123/jpah.2017-0128
pubmed_235_20664
OBJECTIVES An inhaled corticosteroid (ICS)-long-acting beta-2 agonist (LABA) combination has become the standard of care in asthma. Various ICS-LABAs are commercially available providing the clinician with many choices. A thorough understanding of the clinical efficacy and safety of various formulations will immensely benefit the prescribing doctor to decide the choice of agent. The present systematic review was undertaken to compare the clinical efficacy and safety of formoterol fluticasone (FF) to other ICS/LABA combinations in asthmatics. METHODS The review adhered to the general principles mentioned in the CRD guidance and the PRISMA statement. We searched Medline, Embase, and Cochrane Controlled Trials Register databases on the efficacy of FF in treating asthma compared with other ICS-LABAs. A total of 138 trials identified initially. Only trials comparing the efficacy and safety of FF in comparision with Salmeterol/fluticasone (SF) or Budesonide/Formoterol (BF) were selected. The outcomes compared were onset of bronchodilator action, improvement in lung function, asthma control, asthma-related quality of life and risk of pneumonia. RESULTS Sixteen studies were included in the final analysis. FF therapy provided faster onset of bronchodilatation than SF. A better improvement in lung function was seen with FF inhaler use as compared with comparators in two studies. Patients using the FF inhaler had a non-inferior asthma control and asthma-related quality of life. Pneumonia risk was least with FF usage. CONCLUSION FF provides faster onset of action, numerically superior improvement in lung function and comparable asthma control than other ICS-LABA formulations. FF has better safety evidenced by lower occurrence of pneumonia.
10.1080/02770903.2021.1900864
pubmed_1018_15400
An 8-year-old, female mongrel dog had granulomatous lesions in the skull skin and gingiva of the left mandible. The lesions were macroscopically seen as grayish white papular granulomas, and microscopically consisted to numerous swollen macrophages and a few neutrophils without fibrocaseous necrosis. Macrophages contained many small oval or round-shaped yeast-like cells and a few rod-shaped organisms indicating a narrow based budding in their cytoplasm. The yeast-like cells were 2-5 microns (average 3.5 microns) in diameter, and appeared as a central, spherical, lightly basophilic body surrounded by a clear zone or "halo". The cell wall and central body were stained by the periodic acid-Shiff, Grocott's methenamine silver impregnation, or Gridley fungus method. Immunohistochemically, yeast-like cells were positive to anti-histoplasma yeast antibody, and rod-shaped organisms were positive to anti-histoplasma mycelial antibody. The present paper describes the first case of canine histoplasmosis in Japan.
10.1292/jvms.60.863
pubmed_1048_21357
Intensive forest management, together with fire suppression, have decreased structural complexity and altered dynamics of boreal forests profoundly. Such management threatens forest biodiversity and can reduce the provision of ecosystem services. Although the importance of ecosystem services is widely acknowledged, conservation strategies are hindered by poor knowledge about diversity patterns of service provider species as well as on mechanisms affecting these assemblages at different spatial and temporal scales. In this study, we assessed the effect of disturbance management on forest pollinator communities. To do so, we used a large-scale ecological experiment conducted in the year 2000, where forest complexity was manipulated with different harvest regimes and prescribed fire. Results were consistent with a positive response of pollinators to increasing habitat heterogeneity driven by past disturbances. Harvested sites harbored a diverse pollinator community, and showed higher spatial and temporal turnover in species richness. Conversely, old-growth forest communities were a nested subset of harvested sites and contained half of their total diversity. Variation in community composition (β diversity) was primarily affected by species temporal turnover. Throughout the season, β diversity was controlled by fire and harvesting legacies, which provide environmental heterogeneity in the form of flowering and nesting resources over space and time. Conservation strategies may undervalue ecosystem services in dynamic, naturally disturbance-driven, landscapes when relying solely on undisturbed forests areas. However, maintaining natural dynamics in early successional forests, by emulating natural disturbances at harvesting, hold promise for the conservation of both biodiversity and ecosystem services in boreal forests.
10.1002/eap.1468
pubmed_83_9668
BACKGROUND Calcium channel blockers (CCBs) are used to manage hypertension which is highly prevalent among people with chronic kidney disease (CKD). The treatment for hypertension is particularly challenging in people undergoing dialysis. OBJECTIVES To assess the benefits and harms of calcium channel blockers in patients with chronic kidney disease requiring dialysis. SEARCH METHODS We searched the Cochrane Kidney and Transplant Register of Studies to 27 April 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA All randomised controlled trials (RCTs) and quasi-RCTs that compared any type of CCB with other CCB, different doses of the same CCB, other antihypertensives, control or placebo were included. The minimum study duration was 12 weeks. DATA COLLECTION AND ANALYSIS Two authors independently assessed study quality and extracted data. Statistical analyses were performed using a random-effects model and results expressed as risk ratio (RR), risk difference (RD) or mean difference (MD) with 95% confidence intervals (CI). MAIN RESULTS This review included 13 studies (24 reports) randomising 1459 participants treated with long-term haemodialysis. Nine studies were included in the meta-analysis (622 participants). No studies were performed in children or in those undergoing peritoneal dialysis. Overall, risk of bias was assessed as unclear to high across most domains. Random sequence generation and allocation concealment were at low risk of bias in eight and one studies, respectively. Two studies reported low risk methods for blinding of participants and investigators, and outcome assessment was blinded in 10 studies. Three studies were at low risk of attrition bias, eight studies were at low risk of selective reporting bias, and five studies were at low risk of other potential sources of bias. Overall, the certainty of the evidence was low to very low for all outcomes. No events were reported for cardiovascular death in any of the comparisons. Other side effects were rarely reported and studies were not designed to measure costs. Five studies (451 randomised adults) compared dihydropyridine CCBs to placebo or no treatment. Dihydropyridine CCBs may decrease predialysis systolic (1 study, 39 participants: MD -27.00 mmHg, 95% CI -43.33 to -10.67; low certainty evidence) and diastolic blood pressure level (2 studies, 76 participants; MD -13.56 mmHg, 95% CI -19.65 to -7.48; I2 = 0%, low certainty evidence) compared to placebo or no treatment. Dihydropyridine CCBs may make little or no difference to occurrence of intradialytic hypotension (2 studies, 287 participants; RR 0.54, 95% CI 0.25 to 1.15; I2 = 0%, low certainty evidence) compared to placebo or no treatment. Other side effects were not reported. Eight studies (1037 randomised adults) compared dihydropyridine CCBs to other antihypertensives. Dihydropyridine CCBs may make little or no difference to predialysis systolic (4 studies, 180 participants: MD 2.44 mmHg, 95% CI -3.74 to 8.62; I2 = 0%, low certainty evidence) and diastolic blood pressure (4 studies, 180 participants: MD 1.49 mmHg, 95% CI -2.23 to 5.21; I2 = 0%, low certainty evidence) compared to other antihypertensives. There was no evidence of a difference in the occurrence of intradialytic hypotension (1 study, 92 participants: RR 2.88, 95% CI 0.12 to 68.79; very low certainty evidence) between dihydropyridine CCBs to other antihypertensives. Other side effects were not reported. Dihydropyridine CCB may make little or no difference to predialysis systolic (1 study, 40 participants: MD -4 mmHg, 95% CI -11.99 to 3.99; low certainty evidence) and diastolic blood pressure (1 study, 40 participants: MD -3.00 mmHg, 95% CI -7.06 to 1.06; low certainty evidence) compared to non-dihydropyridine CCB. There was no evidence of a difference in other side effects (1 study, 40 participants: RR 0.13, 95% CI 0.01 to 2.36; very low certainty evidence) between dihydropyridine CCB and non-dihydropyridine CCB. Intradialytic hypotension was not reported. AUTHORS' CONCLUSIONS The benefits of CCBs over other antihypertensives on predialysis blood pressure levels and intradialytic hypotension among people with CKD who required haemodialysis were uncertain. Effects of CCBs on other side effects and cardiovascular death also remain uncertain. Dihydropyridine CCBs may decrease predialysis systolic and diastolic blood pressure level compared to placebo or no treatment. No studies were identified in children or peritoneal dialysis. Available studies have not been designed to measure the effects on costs. The shortcomings of the studies were that they recruited very few participants, had few events, had very short follow-up periods, some outcomes were not reported, and the reporting of outcomes such as changes in blood pressure was not done uniformly across studies. Well-designed RCTs, conducted in both adults and children with CKD requiring both haemodialysis and peritoneal dialysis, evaluating both dihydropyridine and non-dihydropyridine CCBs against other antihypertensives are required. Future research should be focused on outcomes relevant to patients (including death and cardiovascular disease), blood pressure changes, risk of side effects and healthcare costs to assist decision-making in clinical practice.
10.1002/14651858.CD011064.pub2
pubmed_859_2897
Child maltreatment and harsh parenting both include harmful actions by parents toward children that are physical (e.g., spanking, slapping) or emotional (e.g., threatening, yelling). The distinction between these two constructs, in meaning and measurement, is often unclear, leading to inconsistent research and policy. This study systematically identified, reviewed, and compared parent-reported child maltreatment (N = 7) and harsh parenting (N = 18) instruments. The overlap in parenting behaviors was 73%. All physical behaviors that were measured in harsh parenting instruments (e.g., spanking, beating up) were also measured in child maltreatment instruments. Unique physical behaviors measured in maltreatment instruments include twisting body parts and choking. All emotional behaviors in maltreatment instruments were included in harsh parenting instruments, and vice versa. Our findings suggest similar, but not identical, operationalizations of child maltreatment and harsh parenting. Our findings can help guide discussions on definitions, operationalizations, and their consequences for research on violence against children.
10.1177/15248380221134290
pubmed_716_3165
BACKGROUND Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. Bone marrow computed tomography (CT) attenuation may increase in patients with myeloproliferative disorders; however, the actual threshold CT attenuation value predictive of myeloproliferative has not been reported. PURPOSE To determine whether the unenhanced CT attenuation value of the bone marrow may be useful for predicting AML. MATERIAL AND METHODS We retrospectively analyzed patients with AML (n = 56) who underwent unenhanced CT before treatment, and age- and sex-matched controls without any hematologic disease. For each patient, the CT attenuation value (HU) of the iliac bone was measured and compared between the two groups. Receiver operating characteristic (ROC) curve analysis was used to define the cutoff value for predicting AML on all patients, and only on late elderly patients (aged ≥75 years). RESULTS Patients with AML showed higher bone marrow CT attenuation value (131.4 ± 58.3 vs. 53.9 ± 67.2 HU; P < 0.001), compared to the controls. The sensitivity and specificity for the diagnosis of AML in all patients were 78.6% and 80.4%, respectively, at a threshold value of 90 HU, whereas they were 83.3% and 91.7%, respectively, at 40 HU in late elderly patients. CONCLUSION The iliac bone CT attenuation value was elevated in patients with AML and may be useful for predicting AML.
10.1177/02841851221135154
pubmed_936_25757
OBJECTIVE Rescuing severe trauma cases is extremely demanding. The present study purposed to analyze the efficiency of trauma management at Emergency Centre, University Clinical Centre of Serbia, Belgrade, included outcome within 28 days. METHODS This retrospective study involved 131 intensive care unit trauma cases with total Injury Severity Score ≥16, in terms of administrating the two strategies: (i) definitive surgical repair and (ii) damage control laparotomy. RESULTS The damage control laparotomy cases revealed statistically higher Injury Severity Score and APACHE II scores, significant brain dysfunction, and hemorrhagic shock on arrival (p<0.001). In addition, the damage control laparotomy had a higher rate of respiratory complications, multiple organ deficiency syndrome, and surgical wound complications (p=0.017, <0.001, and 0.004, respectively), with more days on mechanical ventilation (p=0.003). Overall mortality was 29.8%. Although higher early mortality within ≤24 h in the damage control laparotomy (p=0.021) had been observed, no difference between groups (p=0.172) after the 4th day of hospitalization was detected. CONCLUSIONS Trauma patients have a high mortality rate in the 1st hours after the incident. Compelling evidence linking host and pathogen factors, such as mitochondrial apoptosis pathways, appears to correlate with loss of organ dysfunction, both cytopathologically and histopathologically. Adequate selection of patients necessitating damage control laparotomy, allowed by the World Society of Emergency Surgery, abdominopelvic trauma classifications, and improvements in resuscitation, may improve the results of severe trauma treatment.
10.1590/1806-9282.20220216
pubmed_306_17276
Although high-risk sport participants are typically considered a homogenous risk-taking population, attitudes to risk within the high-risk domain can vary considerably. As no validated measure allows researchers to assess risk taking within this domain, we validated the Risk Taking Inventory (RTI) for high-risk sport across four studies. The RTI comprises seven items across two factors: deliberate risk taking and precautionary behaviors. In Study 1 (n = 341), the inventory was refined and tested via a confirmatory factor analysis used in an exploratory fashion. The subsequent three studies confirmed the RTI's good model-data fit via three further separate confirmatory factor analyses. In Study 2 (n = 518) and in Study 3 (n = 290), concurrent validity was also confirmed via associations with other related traits (sensation seeking, behavioral activation, behavioral inhibition, impulsivity, self-esteem, extraversion, and conscientiousness). In Study 4 (n = 365), predictive validity was confirmed via associations with mean accidents and mean close calls in the high-risk domain. Finally, in Study 4, the self-report version of the inventory was significantly associated with an informant version of the inventory. The measure will allow researchers and practitioners to investigate risk taking as a variable that is conceptually distinct from participation in a high-risk sport.
10.1123/jsep.35.5.479
pubmed_431_18169
BACKGROUND We report a patient-centered intervention study in 9 municipalities of rural Nicaragua aiming at a reduction of internalized social stigma in new AFB positive tuberculosis (TB) patients diagnosed between March 2004 and July 2005. METHODS Five out of 9 municipal teams were coached to tailor and introduce patient-centered package. New TB patients were assigned to the intervention group when diagnosed in municipalities implementing effectively at least TB clubs and home visits. We compared the changes in internalized stigma and TB treatment outcome in intervention and control groups. The internalized stigma was measured through score computed at 15 days and at 2 months of treatment. The treatment results were evaluated through classical TB program indicators. In all municipalities, we emphasized process monitoring to capture contextual factors that could influence package implementation, including stakeholders. RESULTS TB clubs and home visits were effectively implemented in 2 municipalities after June 2004 and in 3 municipalities after January 2005. Therefore, 122 patients were included in the intervention group and 146 in the control group. After 15 days, internalized stigma scores were equivalent in both groups. After 2 months, difference between scores was statistically significant, revealing a decreased internalized stigma in the intervention group and not in the control group. CONCLUSION This study provides initial evidences that it is possible to act on TB patients' internalized stigma, in contexts where at least patient centered home visits and TB clubs are successfully implemented. This is important as, indeed, TB care should also focus on the TB patient's wellbeing and not solely on TB epidemics control.
10.1186/1471-2458-8-154
pubmed_304_16591
Zoledronic acid (ZOL) has proved activity in bone metastases from prostate cancer through inhibition of mevalonate pathway and of prenylation of intracellular proteins. We have reported that ZOL synergizes with R115777 farnesyltransferase inhibitor (FTI, Zarnestra) in inducing apoptosis and growth inhibition on epidermoid cancer cells. Here, we have studied the effects of the combination of these agents in prostate adenocarcinoma models and, specifically, on androgen-independent (PC3 and DU145) and -dependent (LNCaP) prostate cancer cell lines. We have found that ZOL and R115777 were synergistic in inducing both growth inhibition and apoptosis in prostate adenocarcinoma cells. These effects were paralleled by disruption of Ras-->Erk and Akt survival pathways, consequent decreased phosphorylation of both mitochondrial bcl-2 and bad proteins, and caspase activation. Finally, ZOL/R115777 combination induced cooperative effects also in vivo on tumor growth inhibition of prostate cancer xenografts in nude mice with a significant survival increase. These effects were paralleled by enhanced apoptosis and inactivation of both Erk and Akt. In conclusions, the combination between ZOL and FTI leads to enhanced anti-tumor activity in human prostate adenocarcinoma cells likely through a more efficacious inhibition of ras-dependent survival pathways and consequent bcl-related proteins-dependent apoptosis.
10.1002/jcp.20960
pubmed_527_8384
AIM The benefit of direct, as opposed to calculated, low density lipoprotein -cholesterol (LDL-C) measurement remains unclear. This study compared the biological variability of direct LDL in patients with type 2 diabetes (T2DM) on equivalent doses of the short half-life statin, simvastatin or the longer half-life statin, atorvastatin. METHODS A cross-over study of biological variation of lipids in 26 patients with T2DM taking either simvastatin 40 mg (n = 10) or atorvastatin 10 mg. After 3 months on one statin, fasting lipids were measured on 10 occasions over a 5-week period. The same procedure was then followed on the other statin. The variability of LDL-C was established using a Beckman direct assay. RESULTS As a group, mean LDL was no different between statins (mean +/- s.d.) (1.69 +/- 0.60 mmol/l simvastatin vs. 1.67 +/- 0.60 mmol/l atorvastatin, p = 0.19). However, in all patients, the intraindividual biological variability of LDL while taking simvastatin was markedly higher than with atorvastatin (average s.d. = 0.17 mmol /l simvastatin vs. 0.01 mmol/l, p < 0.0001). Friedewald calculated LDL variability was no different between statins (average s.d. = 0.34 mmol /l simvastatin vs. 0.21 mmol/l atorvastatin, p = 0.19). CONCLUSIONS In contrast to calculated values, direct measurement revealed LDL to be much more stable (the s.d. being an order of magnitude) in T2DM patients taking atorvastatin rather than simvastatin. This means LDL targets can be consistently met with less lipid monitoring using atorvastatin rather than simvastatin. Direct LDL measurement may therefore have a particular role in monitoring patients on statin treatment.
10.1111/j.1463-1326.2009.01190.x
pubmed_522_5177
BACKGROUND Whilst many authors have previously suggested that older people are under-represented in the investigation and management of lung cancer, few data are available as to the effect of age on the subsequent investigation and management of a patient with an abnormal chest radiograph. METHODS During a 3-month period in a university teaching hospital, all abnormal chest radiographs suggestive of a possible diagnosis of lung cancer were identified, and patients subsequently followed to determine investigation, management and date of death over a 5-year period. RESULTS Thirty-seven younger (</=69 years, median age 62 years) and 43 older patients (>/=70 years, median age 80 years) were identified. Of the 80 patients with a possible bronchial carcinoma only 59% had a further chest radiograph performed. Bronchoscopy was performed in 34% of patients, but a biopsy of the lesion was undertaken in only 24% of patients. Sixteen of the 80 patients, irrespective of what investigations had been undertaken, were referred for an oncological or surgical opinion. During the study period (3 months), 24% of the patients died. At 6, 24 and 60 months, respectively, the total deaths were 40, 78 and 88%. CONCLUSION Older patients compared with those aged less than 70 years were less likely to be investigated, further, were more likely to be managed differently (i.e., less aggressively) and more likely to die within each time interval. In more of the older group a presumed death certificate diagnosis of pneumonia was made. When an abnormal chest radiograph raises the possibility of an underlying bronchial carcinoma, the finding of this study suggests that an ageist attitude influences the subsequent management of some patients.
10.1159/000081427
pubmed_611_13438
CAAT/enhancer-binding proteins (C/EBPs) play an important role in the regulation of gene expression in insulin-responsive tissues. We have found that a complex containing C/EBPbeta interacts with an insulin response sequence in the insulin-like growth factor-binding protein-1 (IGFBP-1) gene and that a C/EBP-binding site can mediate effects of insulin on promoter activity. Here, we examined mechanisms mediating this effect of insulin. The ability of insulin to suppress promoter activity via a C/EBP-binding site is blocked by LY294002, a phosphatidylinositol 3-kinase inhibitor, but not by rapamycin, which blocks activation of p70(S6 kinase). Dominant negative phosphatidylinositol 3-kinase and protein kinase B (PKB) block the effect of insulin, while activated PKB suppresses promoter function via a C/EBP-binding site, mimicking the effect of insulin. Coexpression studies indicate that insulin and PKB suppress transactivation by C/EBPbeta, but not C/EBPalpha, and that N-terminal transactivation domains in C/EBPbeta are required. Studies with Gal4 fusion proteins reveal that insulin and PKB suppress transactivation by the major activation domain in C/EBPbeta (AD II), located between amino acids 31 and 83. Studies with E1A protein indicate that interaction with p300/CBP is required for transactivation by AD II and the effect of insulin and PKB. Based on a consensus sequence, we identified a PKB phosphorylation site (Ser(1834)) within the region of p300/CBP known to bind C/EBPbeta. Mammalian two-hybrid studies indicate that insulin and PKB disrupt interactions between this region of p300 and AD II and that Ser(1834) is critical for this effect. Signaling by PKB and phosphorylation of Ser(1834) may play an important role in modulating interactions between p300/CBP and transcription factors and mediate effects of insulin and related growth factors on gene expression.
10.1074/jbc.M008542200
pubmed_122_18598
This study examined whether tocotrienol supplementation to corticosterone-treated male rats could prevent foetal loss in females upon their mating. Epididymides of adult male Sprague-Dawley (SD) rats with proven fertility were surgically separated at the testis-caput junction. Twenty-four hours post-surgery, these animals received for 7 days either: tocopherol-stripped corn oil (Control), corticosterone 25 mg/kg s.c. (CORT), CORT 25 mg/kg s.c. and tocotrienol-rich fraction (TRF) 100 mg/kg orally (CORT + TRF) or TRF 100 mg/kg orally (TRF). On day 8, males were cohabited with proestrus females. A spermatozoa-positive vaginal smear indicated pregnancy. Males were euthanised for analysis of testosterone and antioxidant activities. Reproductive organs were weighed. On day 8 of pregnancy, females were laparotomised to count the number of implantation sites. Pregnancy was continued until term. Number of pups delivered and their weights were determined. Data were analysed using ANOVA. Malondialdehyde levels were significantly lower in CORT + TRF group compared with CORT group. Enzymatic antioxidant activities, testosterone level and reproductive organ weights were significantly higher in CORT + TRF group compared with CORT group. Number of implantation sites and live pups delivered, and their birth weights from females mated with CORT + TRF males were significantly higher compared to CORT group. Therefore, TRF prevents foetal loss in females mated with CORT + TRF-treated males.
10.1111/and.13199
pubmed_47_14
Forty-one patients out of a larger series undergoing elective surgery were examined for the presence of venous thrombosis in the legs by means of the (125)I-fibrinogen technique. The radioisotope data were analysed by three different methods. The percentage uptake was calculated and, by the generally accepted difference of 15%, 22 patients had evidence of thrombosis. The statistical index, which takes account of the errors due to radioactivity counting inherent in the percentage uptake calculation, indicated thrombosis in 36 patients. The relative uptake index, which allows for the errors due to unequal distribution of radioactivity throughout the normal limb as well as the errors due to radioactivity counting, provided evidence of thrombosis in a total of 34 patients, compared with only 22 patients when assessed by the "15%" criterion.
10.1136/bmj.3.5825.500
pubmed_770_3491
Rabbit liver (male) microsomal metabolism of 10 microM [4,5,9,10-3H]-1-nitropyrene (1NP) was investigated. The total metabolism was not appreciably different with rates of 4.44 +/- 0.45, 3.98 +/- 0.19, 3.90 +/- 0.16, and 3.75 +/- 0.27 nmol/min/mg protein, respectively, for microsomes from phenobarbital, Aroclor-1254, ethanol-treated, and untreated rabbits. However, a more noticeable difference was found in the formation of specific metabolites. Phenobarbital treatment induced changes which favored 1-nitropyrene-3-ol formation, and Aroclor-1254 and ethanol-induced changes which favored 1-nitropyren-6-ol and 1-nitropyren-8-ol formation. 1NP was incubated with untreated microsomes and alpha-naphthoflavone, an inhibitor of rabbit cytochrome P-450 form 6 at low concentrations (less than 1 microM), and an activator of form 3c at high concentrations. The presence of alpha-naphthoflavone changed the profile of metabolites while not affecting the total metabolism. Using purified isozymes of rabbit P-450, we found the constitutive form 3b metabolized 1NP at the highest rate with a catalytic activity of 26.8 nmol/min/nmol P-450. Forms 2 and 6 exhibited rates of 2 and 2.2 nmol/min/nmol P-450. Forms 3a, 3c, and 4 had rates about 50- to 300-fold lower than form 3b. High performance liquid chromatography was used to identify the metabolites when the incubations were carried out in the presence of purified rabbit epoxide hydrolase. With form 6, 54% of the metabolites were accounted for as 1-nitropyren-3-ol, while with form 3b, 73% of the metabolites were 1-nitropyren-6-ol and 1-nitropyren-8-ol. The K-region dihydrodiols were formed by forms 2 and 3b, but not by forms 3c or 6. These results demonstrate that 1NP is a preferential substrate for form 3b, and that a preponderance of the metabolism with untreated rabbit liver microsomes can be attributed to this isozyme.
pubmed_770_3491
pubmed_263_16547
OBJECTIVE To quantify modification of functional capacity in a three year period in a group of patients with rheumatoid arthritis (RA) using HAQ and EPM-ROM inventories. METHODS Forty patients with RA on methotrexate (MTX) as disease-modifying anti rheumatic drug (DMARD) were followed for up to three years. The functional status was assessed at the beginning and end of the period by HAQ and EPM-ROM. RESULTS Thirty two patients were retrieved, with initial HAQ score of 1.14±0.49 (mean±SD) and EPM-ROM score of 5.8±2.75. After an average period of three years, the HAQ score was 1.13±0.49 and EPM-ROM score, 6.81±3.66. In the subgroup of seven patients submitted to orthopedic surgery, HAQ score decreased from 0.84±0.72 to 1.64±0.56 and the EPM-ROM score, from 5.8±1.80 to 8.3±0.74. In the subgroup of non-operated patients, HAQ score varied from of 1.2±0.45 to 1.07±0.70 and EPM-ROM score, from 5.7±3.06 to 6.4±3.90. CONCLUSION In a group of RA patients in use of only MTX as DMARD, there was little change on HAQ score and EPM-ROM scores over the average period of three years. Worsening functional capacity was observed in the group of operated patients in comparison to the not operated ones. This fact alerts us to the need for use of broader therapeutic regimens availability of musculoskeletal surgeries in a timely manner in patients with RA.
pubmed_263_16547
pubmed_880_10706
The adsorption and reaction of NO(2) on BaO (<1, ∼3, and >20 monolayer equivalent (MLE))/Pt(111) model systems were studied with temperature programmed desorption (TPD), X-ray photoelectron spectroscopy (XPS), and infrared reflection absorption spectroscopy (IRAS) under ultra-high vacuum (UHV) as well as elevated pressure conditions. NO(2) reacts with sub-monolayer BaO (<1 MLE) to form nitrites only, whereas the reaction of NO(2) with BaO (∼3 MLE)/Pt(111) produces mainly nitrites and a small amount of nitrates under UHV conditions (P(NO(2))≈ 1.0 × 10(-9) Torr) at 300 K. In contrast, a thick BaO (>20 MLE) layer on Pt(111) reacts with NO(2) to form nitrite-nitrate ion pairs under the same conditions. At elevated NO(2) pressures (≥1.0 × 10(-5) Torr), however, BaO layers at all these three coverages convert to amorphous barium nitrates at 300 K. Upon annealing to 500 K, these amorphous barium nitrate layers transform into crystalline phases. The thermal decomposition of the thus-formed Ba(NO(x))(2) species is also influenced by the coverage of BaO on the Pt(111) substrate: at low BaO coverages, these species decompose at significantly lower temperatures in comparison with those formed on thick BaO films due to the presence of a Ba(NO(x))(2)/Pt interface where the decomposition can proceed at lower temperatures. However, the thermal decomposition of the thick Ba(NO(3))(2) films follows that of bulk nitrates. Results obtained from these BaO/Pt(111) model systems under UHV and elevated pressure conditions clearly demonstrate that both the BaO film thickness and the applied NO(2) pressure are critical in the Ba(NO(x))(2) formation and subsequent thermal decomposition processes.
10.1039/c0cp02983a
pubmed_602_10002
The WARTS gene encodes a kinase that localizes to the mitotic apparatus of a dividing cell. Named WARTS after the growths that develop in the eyes of Drosophila in which the gene is deleted. WARTS is also implicated as a tumor suppressor in mice and humans. In this issue of Oncogene, Iida et al. describe experiments suggesting that, in addition to a role in regulating mitosis, WARTS functions to prevent further rounds of DNA synthesis and mitosis in tetraploid cells. As well as opening up new possibilities of exploring the as yet ill-defined mechanistic basis of the tetraploidy checkpoint, the involvement of a tumor-suppressor gene in this checkpoint supports its importance as a safeguard against the acquisition of genomic instability, a key event in the progression to cancer.
10.1038/sj.onc.1207686
pubmed_1110_7693
BACKGROUND The Calibrated Automated Thrombography (CAT) is an in vitro thrombin generation (TG) assay that holds promise as a valuable tool within clinical diagnostics. However, the technique has a considerable analytical variation, and we therefore, investigated the analytical and between-subject variation of CAT systematically. Moreover, we assess the application of an internal standard for normalization to diminish variation. METHODS 20 healthy volunteers donated one blood sample which was subsequently centrifuged, aliquoted and stored at -80 °C prior to analysis. The analytical variation was determined on eight runs, where plasma from the same seven volunteers was processed in triplicates, and for the between-subject variation, TG analysis was performed on plasma from all 20 volunteers. The trigger reagents used for the TG assays included both PPP reagent containing 5 pM tissue factor (TF) and PPPlow with 1 pM TF. Plasma, drawn from a single donor, was applied to all plates as an internal standard for each TG analysis, which subsequently was used for normalization. RESULTS The total analytical variation for TG analysis performed with PPPlow reagent is 3-14% and 9-13% for PPP reagent. This variation can be minimally reduced by using an internal standard but mainly for ETP (endogenous thrombin potential). The between-subject variation is higher when using PPPlow than PPP and this variation is considerable higher than the analytical variation. CONCLUSION TG has a rather high inherent analytical variation but considerable lower than the between-subject variation when using PPPlow as reagent.
10.1080/00365513.2018.1427280
pubmed_993_2263
The site of greatest airway deformation in dog lungs was located during maximum expiratory flow by use of tantalum bronchography, fiberoptic bronchoscopy, and airway pressure measurements. A series of area vs. transmural pressure curves for each of these segments of the airway was produced after stepwise changes in transmural pressure. Measurements of area were made using cinephotography to elucidate the effect of time on airway compliance. The maximum flow rate was calculated using the t = 0.1 s compliance curve of the airway. An equation was derived so that maximum flow (V) could be calculated from the area (A) and transmural pressure (Ptm) of the flow-limiting segment. This equation, V = K-A square root of Ptm, implied that if V were constant then A must vary as Ptm-1/2. It was demonstrated that the area-transmural pressure curve of the flow-limiting segment showed this relationship between A and Ptm and that the flow calculated from this equation and the data from the A-Ptm curve gave flows identical to those measured during maximum expiration. The phenomena of effort-independent flow and negative effort dependence are also explained in terms of the area-transmural pressure curve of the flow-limiting segment.
10.1152/jappl.1975.38.6.1002
pubmed_1064_7729
INTRODUCTION The causes of transcristal conduction (TC) in patients with atrial flutter (AFL) are unknown. METHODS AND RESULTS In two groups of patients referred for AFL ablation, 36 had cavotricuspid isthmus (CTI) dependent flutter (Group I) and 24 had lower (n = 21) or upper loop reentry (n = 5) (Group II). After ablation, isthmus block was evaluated by pacing from the coronary sinus (CS) and low lateral right atrium and by alternative techniques, including mapping with electrodes spanning the CTI or electroanatomic mapping. After bidirectional CTI block was verified, 21/36 (58%) in Group I showed TC with CS pacing, including low TC in 16 (including 11 showing "pseudo" CTI conduction), higher TC in 6 and multiple breaks in 3. However, 8 with low TC during CS pacing showed unidirectional block by pacing outside of the CS os. Twelve (50%) in Group II had TC during CS pacing after bidirectional CTI block, with low TC in 5 (2 mimicking residual CTI conduction) and higher breaks in 9. There was no significant difference in the incidence of TC during CS pacing after CTI block between groups. In seven autopsied hearts, the muscle orientation between the proximal CS musculature and Eustachian ridge were examined. Muscular connections between the CS and Eustachian ridge coursing toward the orifice of inferior vena cava were found in one of the hearts. CONCLUSIONS It is concluded that in patients with bidirectional CTI block, pacing from the CS may be associated with TC mimicking a conduction leak through the isthmus. Pacing just outside the CS os helps distinguish pseudo from true isthmus block.
10.1111/j.1540-8159.2005.09421.x
pubmed_443_2798
One of the national health objectives for 2000 (HP2000) is to establish and monitor nonoccupational "sentinel" environmental diseases, including asthma, heatstroke, hypothermia, heavy metal poisoning, pesticide poisoning, carbon monoxide poisoning, acute chemical poisoning, and methemoglobinemia, in at least 35 states (baseline: 0 states in 1990) (objective 11.16). To assess progress toward this objective, the Council of State and Territorial Epidemiologists (CSTE), the Association of Schools of Public Health, and CDC conducted a telephone survey of environmental epidemiologists in each of the 50 states, the District of Columbia, and Puerto Rico during June-August 1997. This report summarizes the results of that survey, which indicate that progress is being made toward the HP2000 objective.
pubmed_443_2798
pubmed_12_18231
Since interleukin-4 (IL-4) displays agonistic effects on both T and B cells, we studied whether this lymphokine is involved in rheumatoid synovitis, a disease characterized by intense T cell infiltration and B cell stimulation. Rheumatoid arthritis synovial fluids (RA SF) contained no (less than 15 pg/ml) or very low amounts (less than 25 pg/ml) of IL-4, as measured by a sensitive and specific enzyme-linked immunosorbent assay. No IL-4 was produced by unstimulated rheumatoid synovial membrane. RA SF were found to inhibit phorbol myristate acetate (PMA)-dependent proliferation of normal peripheral blood lymphocytes (PBL). An inhibitory fraction with an apparent molecular weight of 150 kd was isolated by gel filtration. The inhibitory fraction strongly blocked the proliferation of PBL induced by PMA, PMA + IL-2, or PMA + IL-4. However, this fraction was less effective in blocking the proliferation of PBL induced by PMA + IL-2 + IL-4. High levels of transforming growth factor beta (TGF beta) were found in these RA SF, and an anti-TGF beta antibody was able to partially reduce the inhibitory activity. RA SF were found to inhibit phytohemagglutinin-induced IL-4 production by PBL. These data indicate that IL-4, similar to other T cell lymphokines, cannot be detected in RA SF and that RA SF contains an inhibitory activity, related in part to TGF beta, which blocks mitogen-induced proliferation of PBL, at least in part through an inhibition of T cell-derived lymphokine release.
10.1002/art.1780330819
pubmed_361_4193
Proliferative T cell responses were elicited in a comitogenic assay when purified mAb against CD 18, CD11a, LFA-3, and CD7 were immobilized onto solid plastic surfaces together with submitogenic doses of mAb against the CD3 complex. The proliferative response was associated to the production of IL-2 and to the expression of IL-2R. We explored the possibility that a second signal provided by either PMA or a Ca2+ ionofore could replace the anti-CD3 mAb in the comitogenic assay. Interestingly, our data clearly indicate that PMA but not the ionofore was capable of mediating the co-mitogenic effect in conjunction with solid-bound mAb (CDw18, CD11a, LFA-3, and CD7). We also demonstrate that the mAb (anti-CD4 and anti-CD2) which have been previously described as co-mitogenic in combination with anti-CD3 are capable of eliciting this activating signal in the presence of PMA. These data indicate that mAb to certain cell surface differentiation Ag that in soluble form inhibit T cell function such as LFA-1, LFA-3, and CD2 can under appropriate conditions induce co-mitogenic signals on T cells. Our results support the hypothesis that several cell surface differentiation Ag may participate in conjunction with the T3-Ti complex in the transmembrane signal transduction leading to T cell activation.
pubmed_361_4193
pubmed_1066_17843
BACKGROUND Older adults are particularly vulnerable to the adverse health effects of extreme temperature-related events. A growing body of literature highlights the importance of the natural environment, including air pollution and sunlight, on cognitive health. However, the relationship between exposure to outdoor temperatures and cognitive functioning, and whether there exists any differences across climate region, remains largely unexplored. We address this gap by examining the temperature-cognition association, and whether there exists any variation across climate regions in a national cohort of aging adults. METHODS In this cross-sectional study, we obtained data on temperature exposure based on geocoded residential location of participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. For each participant, this information was linked to their cognitive scores from Word List Learning and Recall tests to assess cognitive functioning. We used distributed lag non-linear models (dlnm) to model temperature effects over 2 days. Multivariable linear regression was used to compute temperature-cognitive functioning associations, adjusted for important covariates. Region-specific ("Dry", "Mediterranean/oceanic", "Tropical" and "Continental") associations were examined by including an interaction term between climate region and temperature. RESULTS Amongst 20,687 individuals (mean age = 67.8; standard deviation = 9.2), exposure to region-specific extreme cold temperatures in the "dry" region (e.g., Arizona) over 2 days was associated with lower cognitive scores (Mean Difference [MD]: -0.76, 95% Confidence Interval [CI]: - 1.45, - 0.07). Associations remained significant for cumulative effects of temperature over 2 days. Extremely cold exposure in the "Mediterranean/oceanic" region (e.g., California) over 2 days was also associated with significantly lower cognitive performance (MD: -0.25, 95% CI: - 0.47, - 0.04). No significant associations were observed for exposure to hot temperatures. Cognitive performance was slightly higher in late summer and fall compared to early summer. CONCLUSION We noted adverse cognitive associations with cold temperatures in traditionally warmer regions of the country and improved cognition in summer and early fall seasons. While we did not observe very large significant associations, this study deepens understanding of the impact of climate change on the cognitive health of aging adults and can inform clinical care and public health preparedness plans.
10.1186/s12889-021-11533-x
pubmed_269_9117
Lutetium-177 ( 177 Lu) dotatate has been offered at Fox Chase Cancer Center since 2017 as part of a clinical trial and then in 2018 as a commercially available cancer therapy, and we thought we were prepared for most 177 Lu issues by the fall of 2020. A single phone call identified that the Radiation Safety Department had not been prepared to address extravasations. Fortunately for the patient and Radiation Safety, the 177 Lu therapies are administered by an infusion nurse and Fox Chase Cancer Center has a robust infusion center. The expertise of our infusion center team helped to quickly identify specific mitigation efforts to employ. A team of radiation safety and diagnostic medical physicists worked together to estimate a tissue dose. Research was also started with the aim of identifying therapeutic 177 Lu extravasations as early as possible. The lessons we learned and plans for future early identification of 177 Lu dotatate extravasations are the basis of this paper.
10.1097/HP.0000000000001558
pubmed_257_12351
In analysis of neuronal activity of g. proreus of dogs brain in response to positive and differentiation conditioned cutaneous stimuli, in 44% of 78 studied neurons "late responses" appeared in the form of impulse activity intensification elicited by a positive conditioned stimulus after the end of eating and by a differentiation one--during conditioned signal action; it persisted in different neurones for 30--60 s. By means of various functional tests it has been shown that these reactions are a neurophysiological correlate of animals emotional state gradient.
pubmed_257_12351
pubmed_787_8963
BACKGROUND There are a number of practice areas highlighted in the literature as important for the care of critically ill patients. However, the current implementation of evidence into clinical practice for these areas is largely unknown. The development of clinical practice guidelines can translate the current evidence into useful tools to guide clinicians in providing evidence based care. AIM To identify existence of current guidelines and informal routine procedures and clinicians' views of same within New South Wales (NSW) Intensive Care Units (ICUs) and High Dependency Units (HDUs) for 11 practice areas, namely, bowel management, endotracheal tube (ETT) stabilisation, tracheostomy tube stabilisation, feeding, analgesia, sedation, thromboembolic prevention, head of bed elevation, ulcer prophylaxis and glucose control. METHOD A telephone survey conducted with a representative from NSW ICUs and HDUs. RESULTS There was variation in the number of guidelines and informal routine procedures reported for the 11 practice areas within the study units. Larger ICUs (Joint Faculty of Intensive Care Medicine Level II and Level III) and those who employed an onsite CNC were significantly more likely to have formal guidelines in place. Overall, there were very few audits reportedly conducted for the 11 practice areas. Bowel management was the area of practice most respondents reported as a neglected area of critical care nursing practice and the one they were least satisfied with. CONCLUSION This survey provides a baseline of current practice and guideline use within NSW ICUs and HDUs. It also highlights areas for consideration to further develop clinical practice guidelines that could benefit critically ill patients.
10.1016/j.aucc.2009.10.001
pubmed_901_1705
Possible alteration in the ratio of the long and short forms of initiation factor IF-3 (FEBS Lett. 79, 264-275, 1977) during the growth cycle of Escherichia coli was examined. The ratio was found to remain unchanged between the exponential and stationary growth phases. Contrary to an earlier report (Eur. J. Biochem. 29, 319-325, 1972), the total amount of IF-3 relative to the ribosome content in stationary phase cells was essentially the same as in midlogarithmic phase cells. The activity of IF-3, assayed after its separation from other initiation factors by chromatography, was also the same in extracts from midlogarithmic and stationary phase cells. The data show that in Escherichia coli the ratio of IF-3/ribosome is maintained constant. The ribosomes themselves have been shown to retain virtually full activity in vitro during this transition indicating that growth-cycle-dependent biochemical modifications of the ribosome do not affect its protein synthetic capacity per se.
10.1111/j.1432-1033.1978.tb12020.x
pubmed_733_10521
The Burkholderia cepacia complex is a diverse group of human pathogens that cause life-threatening lung infections in patients with cystic fibrosis or chronic granulomatous disease, and in patients requiring intensive care. Most previous antimicrobial susceptibility studies of these bacteria were performed before recent major revisions in the taxonomy of these bacteria. We determined the in vitro susceptibility of 65 B. cepacia complex isolates from clinical and environmental sources, representing six genomovars. Although intrinsic resistance is considered to be a common feature of the B. cepacia complex, MICs of individual antimicrobials varied widely and resistance was not exhibited by all members of the group.
10.1093/jac/dkf137
pubmed_14_10346
A 62-year-old man was admitted to hospital with general malaise, arthralgia, edema, and high-grade fever. He was diagnosed as dermatomyositis because of typical skin rashes and muscle weakness. His symptoms were improved by high-doses of prednisolone and cyclosporin A, with the exception of the skin rash over the back. High-grade fever developed again when tapering prednisolone. His condition deteriorated gradually. Paresthesia, hypothyroidism, metabolic acidosis, and disseminated intravascular coagulopathy occurred, and he died eight months after the first admission. Postmortem examination revealed intravascular proliferation of atypical mononuclear cells in the lumens of small vessels in all organs. Intravascular lymphomatosis (B cell type) was diagnosed.
10.2169/internalmedicine.41.241
pubmed_176_4956
Monoubiquitylation of the homotrimeric DNA sliding clamp PCNA at lysine residue 164 (PCNA(K164)) is a highly conserved, DNA damage-inducible process that is mediated by the E2/E3 complex Rad6/Rad18. This ubiquitylation event recruits translesion synthesis (TLS) polymerases capable of replicating across damaged DNA templates. Besides PCNA, the Rad6/Rad18 complex was recently shown in yeast to ubiquitylate also 9-1-1, a heterotrimeric DNA sliding clamp composed of Rad9, Rad1, and Hus1 in a DNA damage-inducible manner. Based on the highly similar crystal structures of PCNA and 9-1-1, K185 of Rad1 (Rad1(K185)) was identified as the only topological equivalent of PCNA(K164). To investigate a potential role of posttranslational modifications of Rad1(K185) in DNA damage management, we here generated a mouse model with a conditional deletable Rad1(K185R) allele. The Rad1(K185) residue was found to be dispensable for Chk1 activation, DNA damage survival, and class switch recombination of immunoglobulin genes as well as recruitment of TLS polymerases during somatic hypermutation of immunoglobulin genes. Our data indicate that Rad1(K185) is not a functional counterpart of PCNA(K164).
10.1371/journal.pone.0016669
pubmed_481_11519
The phage Mu transposase (MuA) binds to the ends of the Mu genome during the assembly of higher order nucleoprotein complexes. We investigate the structure and function of the MuA end-binding domain (Ibetagamma). The three-dimensional solution structure of the Ibeta subdomain (residues 77-174) has been determined using multidimensional NMR spectroscopy. It comprises five alpha-helices, including a helix-turn-helix (HTH) DNA-binding motif formed by helices 3 and 4, and can be subdivided into two interacting structural elements. The structure has an elongated disc-like appearance from which protrudes the recognition helix of the HTH motif. The topology of helices 2-4 is very similar to that of helices 1-3 of the previously determined solution structure of the MuA Igamma subdomain and to that of the homeodomain family of HTH DNA-binding proteins. We show that each of the two subdomains binds to one half of the 22 bp recognition sequence, Ibeta to the more conserved Mu end distal half (beta subsite) and Igamma to the Mu end proximal half (gamma subsite) of the consensus Mu end-binding site. The complete Ibetagamma domain binds the recognition sequence with a 100- to 1000-fold higher affinity than the two subdomains independently, indicating a cooperative effect. Our results show that the Mu end DNA-binding domain of MuA has a modular organization, with each module acting on a specific part of the 22 bp binding site. Based on the present binding data and the structures of the Ibeta and Igamma subdomains, a model for the interaction of the complete Ibetagamma domain with DNA is proposed.
10.1093/emboj/16.24.7532
pubmed_108_5724
An increasing body of evidence has revealed that the aberrant expression of microRNAs (miRNAs/miRs) is involved in the development and progression of ovarian cancer (OC). miR‑183 has been demonstrated to act as a tumor suppressor and oncogene in various types of human cancers. However, the biological role of miR‑183 in OC still remains unclear. The aim of the present study was to investigate the role of miR‑183 and evaluate its underlying mechanism in OC. In the present study, miR‑183 was observed to be upregulated in OC tissues and cell lines as determined by reverse transcription‑quantitative polymerase chain reaction. The effects of miR‑183 on OC were further investigated via western blotting, MTT, wound healing, Transwell and immunofluorescence analyses. Downregulation of miR‑183 markedly inhibited cell proliferation, migration and invasion, and promoted apoptosis in OC cells. Furthermore, it was initially confirmed that mothers against decapentaplegic homolog 4 (Smad4) was identified as an efficient target of miR‑183 by luciferase activity assay. Finally, the results revealed that miR‑183 directly regulated biological function via the transforming growth factor (TGF)‑β/Smad4 signaling pathway in OC cells. In conclusion, the results of the present study suggested that miR‑183 exerted tumor‑promoting roles in OC, at least partially by regulating Smad4 via the TGF‑β/Smad4 signaling pathway. Therefore, miR‑183 may serve as a potential target for the diagnosis and prognosis of OC.
10.3892/ijmm.2019.4082
pubmed_1019_12936
OBJECTIVE To evaluate the benefit of placement of dual double-J stents following high-pressure balloon angioplasty for treatment of ureter-ileum anastomosis stricture after total bladder resection. METHODS Seventeen patients (11 males and 6 females, mean age 56.65±6.28 years, 23 sides) undergoing total bladder resection were included in this study. Unilateral and bilateral ureteral stricture occurred postoperatively in 11 and 6 patients, respectively; 13 patients had ureter-ileum bladder anastomosis stricture after ileal bladder substitution, and 4 patients had ureter-ileum stricture after orthotopic construction of ileal neobladder. The control group consisted of 21 patients undergoing open surgery. RESULTS In the double-J stenting group, the effective rate was 82.6% (19/23), similar to that of 85.7% (18/21) in the control group (P>0.05). Compared with the control group, the stenting group showed a significantly reduced mean time of operation (87.42±10.35 min vs 34.12±7.52 min, P<0.05), intraoperative blood loss (203.16±32.67 ml vs 21.54±6.15 ml, P<0.05), and mean postoperative hospital stay (10.12±1.19 vs 3.24±0.35 days, P<0.05). CONCLUSION As a safe and minimally invasive approach to the management of ureter-ileum bladder anastomosis stricture, placement of dual double-J stents following high-pressure balloon angioplasty produces a effect comparable with that of open surgery.
pubmed_1019_12936
pubmed_433_21430
Post-traumatic stress disorder (PTSD) is a severe chronic mental illness that develops in individuals exposed to life-threatening trauma and is characterized by hyperarousal, flashbacks and nightmares. The serotonergic (5-HT) and noradrenergic (NE) systems are deeply involved in the pathogenesis of PTSD. We have previously reported a novel anxiolytic compound, ACH-000029, that modulates 5-HT and α1-adrenergic receptors and induces acute anxiolytic-like effects in rodents. Here, we investigated the potential of ACH-000029 to prevent anxiety-like behavior in the single prolonged stress (SPS) PTSD model. Mice were subjected to the SPS procedure, followed by a 7-day treatment with ACH-000029 and, for comparison, with the α1-adrenergic antagonist prazosin. Animals were behaviorally assessed using social interaction, elevated plus maze and open field tests. Interestingly, treatment with ACH-000029 but not with prazosin ameliorated the SPS-induced sociability impairment and anxiety-like behavior. The brain-wide c-fos mapping, used as a surrogate for brain activity, indicated the brain structures that were altered by SPS and putatively involved in the anxiolytic-like effect of ACH-000029. The SPS protocol produced long-lasting impairment of regions involved in stress-anxiety response, such as the amygdala, prefrontal cortex, globus pallidus and superior colliculus. ACH-000029 treatment reversed the SPS-induced c-fos changes in the globus pallidus, lateral septum and entorhinal cortex and exclusively modulated c-fos levels in subregions from the retrosplenial cortex, cerebellum, superior colliculus and ventromedial hypothalamus. These results support the hypothesis that the dual regulation of 5-HT and α1-adrenergic receptors is required to alleviate PTSD symptoms and suggest a possible role of ACH-000029 as a PTSD treatment.
10.1016/j.neuropharm.2019.107912
pubmed_939_17296
With a growing number of patients on ticagrelor therapy after stent implantation, we observe many cases of side effects of the drug, mostly dyspnoea and bradycardia. In our article we present 2 patients, in which the symptoms were particularly severe. Then we describe possible mechanisms of these complications, explain how to carry out differential diagnosis, discuss when to switch ticagrelor to other antiplatelet drug and finally we present the way to deal with the symptoms.
10.1177/1179547620956634
pubmed_1108_23304
Brain edema is still one of the most deleterious sequels of traumatic brain injury (TBI), and its pathophysiology is not sufficiently understood. The goal of the current study was to investigate the role of arginine vasopressin (AVP), also known as antidiuretic hormone (ADH), an important regulator of tissue water homeostasis, for the formation of post-traumatic brain edema, intracranial pressure (ICP), brain damage, and functional deficits following brain trauma. C57/B16 mice (n=112) were subjected to controlled cortical impact (CCI; 8m/s, 1 mm). At 3 min after trauma, animals received 500 ng of the AVP V(1a)-receptor antogonist (deamino-Pen(1), O-Me-Tyr(2), Arg(8)]-Vasopressin) or 500 ng of the AVP V2-receptor antagonist (adamantaneacetyl(1), O-Et-D-Tyr(2),Val(4), Abu(6),Arg(8,9)]-Vasopressin) by intracerebroventricular injection. After trauma, cerebral water content (24 h), ICP (24 h), contusion volume (24 h and 7 days), and functional outcome (1-7 days) were assessed (n=8 per experimental group). Post-traumatic inhibition of AVP V(1A) receptors reduced ICP by 29% (p < 0.05), brain water content by 45% (p < 0.05), and secondary contusion expansion by 37% (p < 0.05), and it significantly improved motor function 6 and 7 days after trauma (p < 0.05). Inhibition of AVP V2 receptors had no significant effect. The current results demonstrate that vasopressin V(1A) receptors are involved in the pathogenesis of brain edema formation and the subsequent development of secondary brain damage after traumatic brain injury. Accordingly, our study suggests that vasopressin V(1A) receptors may represent a novel therapeutic target for the treatment of post-traumatic brain edema and secondary brain damage.
10.1089/neu.2008.0597
pubmed_139_7050
Regional lung density (LD) and lung water (LW) measurements were made with positron transmission and emission tomography (PET) in normal and edematous lung in supine dogs in vivo. A comparison was also made of LD measurements by PET and X-ray CT (used by others to noninvasively assess pulmonary edema). Mean LW was 0.25 +/- 0.06 ml water/ml lung and the mean LD (PET) was 0.32 +/- 0.06 g/ml lung (average ratio of LW to LD was 0.795 +/- 0.041). The LD measurements ranged from 0.25 +/- 0.06 in anterior portions of lung to 0.43 +/- 0.11 g/ml in posterior areas, but the ratio of LW to LD was similar throughout the lung. The LW and LD measurements obtained in both normal and edematous portions of lung were strongly correlated (r = 0.886). Values for LD by PET were consistently higher than values obtained for LD by X-ray CT. These differences are probably due to beam-hardening effects with CT and partial-volume averaging and scattered radiation effects with PET. Nevertheless, PET-LD measurements may be a satisfactory method for following acute changes in LW or for normalizing other PET-derived data.
10.1097/00004728-198609000-00002
pubmed_643_18115
In recent years, transition metal complexes have been developed for catalytical degradation of a phosphate ester bond, particularly in RNA and DNA; however, less consideration has been given for development of complexes for the degradation of a phosphorothioate bond, as they are the foremost used pesticides in the environment and are toxic to human beings. In this context, we have developed copper complexes of benzimidazolium based ligands for catalytical degradation of a series of organophosphates (parathion, paraoxon, methyl-parathion) at ambient conditions. The copper complexes (assigned as N1-N3) were characterized using single X-ray crystallography which revealed that all three complexes are mononuclear and distorted square planner in geometry. Further, the solution state studies of the prepared complexes were carried out using UV-visible absorption, fluorescence spectroscopy, and cyclic voltametry. The complexes N1 and N2 have benzimidazolium ionic liquid as base attached with two 2-mercapto-benzimidazole pods, whereas complex N3 contains a nonionic ligand. The synthesized copper complexes were evaluated for their catalytic activity for degradation of organophosphates. It is interesting that the complex containing the ionic ligand efficiently degrades phosphorothioate pesticides, whereas complex N3 was not found to be appropriate for degradation due to a weaker conversion rate. The organophosphate degradation studies were monitored by recording absorbance spectra of parathion in the presence of catalyst, i.e., copper complexes with respect to time. The parathion was hydrolyzed into para-nitrophenol and diethyl thiophosphate. Moreover, to analyze the inhibition activity of the pesticides toward acetylcholine esterase enzyme in the presence of prepared metal complexes, Ellman's assay was performed and revealed that, within 20 min, the inhibition of acetylcholine esterase enzyme decreases by up to 13%.
10.1021/acs.inorgchem.9b00770
pubmed_484_11466
OBJECTIVE To explore the relationship between evolution of karyotype and clinical progress in myelodysplastic syndromes (MDS) and estimate the clinical outcomes of high risk patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS Continuous karyotyping were performed using short-term culture of bone marrow cells and G-banding technique to follow up 41 cases of MDS patients. RESULTS Karyotype analysis showed that 24 cases (58.5%) had clonal karyotypic abnormalities. In a median follow up of 34 months (7 approximately 72 months), 6 cases had karyotype evolution in 12 cases with clinical deterioration, while only one had karyotype evolution in 18 cases without clinical progression. The involved chromosomes included No. 2, 4, 7, 8, 10, 11, 17 and 21. Six out of 7 patients who received allo-HSCT attained complete remission and their abnormal karyotypes returned to normal. Four patients with clinical remission after therapy attained cytogenetic remission too. CONCLUSION Karyotype evolution showed a strong relationship with clinical progress in MDS patients, and indicated a very poor prognosis. Patients with clinical progress had much higher incidence of clonal evolution than those with relatively stable clinical course. Allo-HSCT should be considered the first choice of therapy for MDS patients with clonal karyotypic abnormalities.
pubmed_484_11466
pubmed_794_20145
Introduction Ischemic Priapism is defined as an abnormally prolonged state of erection, exceeding 6 h, often and irreducible, occurring without any sexual stimulation. Ischemic priapism has a fatal consequence on the sexual function of men if it's not promptly managed. This pathology can cause erectile dysfunction and this can alter the quality of life of patients. Objective The aim of our study was to determine the factors influencing erectile function after treatment of ischemic priapism. Patients and methods This is a ten-year retrospective, descriptive and analytic study of 40 patients who consulted the urology department at the university hospital center for treatment of ischemic priapism (2010-2019). Results We included 40 patients in our study. The mean age was 35.2 [18-62]. Duration of priapism varied from 20 to 360 h (mean 76.6). The most common etiology of priapism was sickle cell disease in 65% of cases. The mean preoperative IIEF-5 score was 23 [21-26]. All patients underwent corporal aspiration with an injection of ephedrine, but detumescence was observed in only 10% of cases. Thirty-six patients had a distal shunt with detumescence in approximately 70% of cases. Eleven patients underwent a distal shunt but seven patients had definitive fibrosis. After the episode of priapism, only eight patients retained normal erectile function. The mean postoperative IIEF-5 score was 14 [ 7-26]. We noted an improvement in erectile function in 8 patients treated with tadalafil. In multivariate analysis, we have demonstrated that a treatment delay exceeding 48 h, fibrosis and the necessity of a distal shunt significantly affects postoperative erectile function (p = 0.001; p = 0.002; p = 0.002 respectively). Conclusion According to our study, delayed management exceeding 48 h, fibrosis and the necessity of a surgical distal shunt are three independent factors affecting erectile function after treatment of ischemic priapism.
10.1016/j.amsu.2022.103696
pubmed_73_11109
Uterine wall tension is thought to be an important determinant of the onset of labor in pregnant women. We characterize human uterine wall tension using ultrasound from the second trimester of pregnancy until parturition and compare preterm, term and twin pregnancies. A total of 320 pregnant women were followed from first antenatal visit to delivery during the period 2000-2004 at the John Hunter Hospital, NSW, Australia. The uterine wall thickness, length, anterior-posterior diameter and transverse diameter were determined by serial ultrasounds. Subjects were divided into three groups: women with singleton pregnancies and spontaneous labor onset, either preterm or term and women with twin pregnancies. Intrauterine pressure results from the literature were combined with our data to form trajectories for uterine wall thickness, volume and tension for each woman using the prolate ellipsoid method and the groups were compared at 20, 25 and 30 weeks gestation. Uterine wall tension followed an exponential curve, with results increasing throughout pregnancy with the site of maximum tension on the anterior wall. For those delivering preterm, uterine wall thickness was increased P < 0.05 compared with term. For twin pregnancies intrauterine volume was increased compared to singletons (P < 0.001), but wall thickness was not. There was no evidence for increased tension in those delivering preterm or those with twin gestations. These data are not consistent with a role for high uterine wall tension as a causal factor in preterm spontaneous labor in singleton or twin gestations. It seems likely that hormonal differences in multiple gestations are responsible for increased rates of preterm birth in this group rather than increased tension.
10.1371/journal.pone.0011037
pubmed_690_6088
In view of variable results on maximal coronary blood flow in stunned myocardium, we studied the pressure-maximal coronary flow (PMCF) relationship in stunned myocardium in 12 anesthetized swine by using intracoronary adenosine (20 micrograms/kg). Subendocardial systolic segment shortening (SS) measured with sonomicrometry was 19 +/- 5% (means +/- SD) at baseline and 7 +/- 6% (P less than 0.01) at 30 min of reperfusion after 15 min of low-flow ischemia, at which time postsystolic shortening was present. Myocardial stunning increased the slope of the PMCF regression line (alpha PMCF) from 3.34 +/- 1.03 to 3.89 +/- 1.33 ml.min-1.mmHg-1 (P less than 0.01). Atrial pacing at 40 beats/min above spontaneous heart rate (n = 6) further reduced subendocardial SS to 6 +/- 6% (P less than 0.05). Dobutamine (4 micrograms.kg-1.min-1; n = 6) increased subendocardial SS to 13 +/- 5% (P less than 0.05) and abolished postsystolic shortening. Both interventions left alpha PMCF unchanged. In conclusion, myocardial stunning was associated with an increase in alpha PMCF that most likely resulted from the decreased contractile function. The absence of an effect of dobutamine may be due to its predominant action on diastolic function.
10.1152/ajpheart.1992.262.6.H1744
pubmed_1082_8139
The author analyzed and evaluated the therapeutic results of unstable pertrochanteric fractures of the femur treated by the method of a T-shaped splint in 14 patients aged 35-65 years. In 78% during treatment redislocation into the varus position occurred. The mean loss of correction was 36 degrees, despite the fact that a rest regime with a lateral spike splint lasted on average for 32.4 days. In 57% a secondary operation with the necessity of respongioplasty was performed, in two cases final corrective revalgization osteotomy had to be performed. The use of a T-shaped splint in the above indication is controversial.
pubmed_1082_8139
pubmed_537_521
Various DNA- and RNA-dependent RNA polymerases have been reported to use oligoribonucleotide primers to initiate nucleic acid synthesis. For the brome mosaic virus RNA-dependent RNA polymerase (RdRp), we determined that in reactions performed with limited GTP concentrations, minus-strand RNA synthesis can be stimulated by the inclusion of guanosine monophosphate or specific oligoribonucleotides. Furthermore, guanylyl-3',5'-guanosine (GpG) was incorporated into minus-strand RNA and increased the rate of minus-strand RNA synthesis. In the presence of GpG, RdRp's Km for GTP decreased from 50 microM to approximately 3 microM while the Kms for other nucleotides were unaffected. These results have implications for the mechanism of initiation by RdRp.
10.1128/JVI.70.10.6826-6830.1996
pubmed_718_4636
The human immunodeficiency virus type 1 (HIV-1) encoded Vpu is a small integral membrane phosphoprotein that functions in the enhancement of viral particle release and has more recently been shown to cause degradation of CD4 at the endoplasmic reticulum. We have demonstrated earlier that Vpu is phosphorylated by the ubiquitous casein kinase-2 (CK-2) in HIV-1 infected cells. The phosphoacceptor sites targeted by CK-2 in Vpu, however, have not been demonstrated and it was unclear whether Vpu was phosphorylated at one or more of its four serine residues. In this study we characterized the CK-2 phosphoacceptor sites in Vpu using recombinant CK-2 for in vitro phosphorylation of recombinant Vpu protein as well as synthetic peptides of Vpu. Phosphorylation of both Ser52 and Ser56 was demonstrated by in vitro phosphorylation using three 54-residue peptides comprising the entire hydrophilic part of Vpu and containing single serine to asparagine transitions in either position 52 or 56. The Km values of CK-2 to these peptides were established, revealing a preferential phosphorylation of Ser56. The Km values are: Ser56 = 31 microM; Ser 52 = 156 microM; wild type = 27 microM. In addition, we studied phosphorylation of Vpu by endogenous CK-2 following in vitro translation in rabbit reticulocyte lysate of wild-type Vpu or a mutant, Vpum2/6, carrying serine to asparagine changes at amino acid positions 52 and 56. The in vivo phosphorylation of Vpu was studied in transiently transfected human embryonic kidney (293) cells. In this system, the mutant Vpum2/6 was not phosphorylated, indicating that the seryl residues of Vpu at amino acid positions 52 and 56, but not those at positions 23 and 61, are phosphorylated by CK-2. The two CK-2 phosphorylation sites are conserved in all known Vpu sequences and represent the consensus Ser52GlyAsn(Glu/Asp)Ser(Glu/Asp)Gly(Glu/Asp)59. Prediction of the secondary structure revealed a conserved alpha-helix-turn-alpha-helix motif for the hydrophilic C-terminal part of Vpu. A structural model for Vpu is proposed in which the membrane anchor precedes a region comprising two amphipathic alpha-helices of opposed polarity, joined by a strongly acidic turn that protrudes into the cytoplasm and contains the CK-2 phosphorylation sites. Possible functional and structural homologies of Vpu to the membrane channel-forming M2 protein of influenza A viruses are discussed.
10.1006/jmbi.1994.1114
pubmed_877_4956
The underlying histopathology is very important in determining patient management, as the histopathology usually has direct repercussions on the treatment response and clinical course. However, the impact of the method used to assess renal biopsies, i.e., light microscopy (LM), immunofluorescence (IF), and electron microscopy (EM), on the occurrence of a difficult biopsy classification in the native kidneys of pediatric nephrotic patients is unknown. A 12-month-old Japanese boy was diagnosed with nephrotic syndrome (NS); he was administered prednisolone (60 mg/m2/day), and a continuous albumin infusion was started. A renal biopsy using LM revealed minimal change. However, an IF study showed granular staining for immunoglobulin G along the glomerular basement membrane. Therefore, he was diagnosed with membranous nephropathy (MN). As his proteinuria was so severe, we started immunosuppressant therapy and continued the albumin infusion for more than 2 months. However, he did not attain complete remission. A month later, EM examination of his renal biopsy showed extensive foot process fusion without electron-dense deposits. Although the result of the IF study suggested MN, the results of the LM and EM studies indicated minimal change. We finally diagnosed the patient with minimal change NS, in consideration of his clinical condition and course. Because of the failure of previous treatments, pulse steroid therapy was started. After five rounds of therapy the patient attained complete remission. A difficult renal biopsy finding classification, dependent on the diagnostic method used, might occur in the native kidneys of pediatric nephrotic patients. Therefore, a diagnosis should be made after considering all renal biopsy findings and the clinical course.
10.1159/000484475
pubmed_525_13694
BACKGROUND Male age-adjusted lung cancer mortality rate is high in Rosario City, Argentina (62.7 per 100,000). METHODS Case-control study involving interviews with 367 male lung cancer patients and 576 controls. RESULTS The histological distribution detected was: squamous cell 39%, adenocarcinoma 34%, small cell carcinoma 13%, and other or no specified cell type 14%. When comparing with the group unlikely to be exposed to occupational carcinogens, a 60% increase in risk was observed for the remaining occupations (P < 0.008). Risks were high for drivers (OR=1.9, CI: 1.1-4.0), construction (OR=2.5, CI: 1.0-5.9), and agricultural workers also (OR=1.8, CI: 1. 1-3.1). In regard to squamous cell carcinoma, increased risks were observed in the metal industry, particularly in welders (OR=2.9, CI: 1.0-10.1) and mechanics (OR=1.8, CI: 0.9-4.2). Smoking was not a substantial confounding effect. CONCLUSIONS Occupational exposures partly account for the high lung cancer mortality rate among male residents of Rosario City.
10.1002/(sici)1097-0274(199910)36:4<437::aid-ajim4>3.0.co;2-c
pubmed_948_15692
The article is devoted to search for indications and more exact differential diagnostic criteria of angiographic methods of diagnosis of pyo-inflammatory diseases of the kidney. Of most informative value is the selective renal arteriography and pharmacophlebography which gave more exact differential diagnostic criteria.
pubmed_948_15692
pubmed_72_7628
Breast cancer resistance protein (BCRP) is a protein belonging to the ATP-binding cassette (ABC) transporter superfamily that has clinical relevance due to its multi-drug resistance properties in cancer. BCRP can be associated with clinical cancer drug resistance, in particular acute myelogenous or acute lymphocytic leukemias. The overexpression of BCRP contributes to the resistance of several chemotherapeutic drugs, such as topotecan, methotrexate, mitoxantrone, doxorubicin and daunorubicin. The Food and Drugs Administration has already recognized that BCRP is clinically one of the most important drug transporters, mainly because it leads to a reduction of clinical efficacy of various anticancer drugs through its ATP-dependent drug efflux pump function as well as its apparent participation in drug resistance. This review article aims to summarize the different research findings on marine natural products with BCRP inhibiting activity. In this sense, the potential modulation of physiological targets of BCRP by natural or synthetic compounds offers a great possibility for the discovery of new drugs and valuable research tools to recognize the function of the complex ABC-transporters.
10.3390/md13042010
pubmed_688_2309
The effect of microinjection of a quaternary opiate antagonist methylnaloxonium (MN) in the lateral ventricle, ventral tegmental area (VTA) and nucleus accumbens (N.Acc.) was examined on the locomotor activation produced by a subcutaneous heroin injection (0.5 mg/kg) in the rat. At this dose heroin typically produced an initial depressant phase (0-30 min) followed by a prolonged hyperactivity (40-120 min). Lateral ventricular injections did not significantly reverse the initial depressant effects of heroin (0-30 min), and a dose of 4 micrograms was needed to reverse the subsequent hyperactivity (40-120 min). The most potent blockade was observed following injections into the N.Acc. where 0.1 microgram significantly reversed the initial depressant effects of heroin (0-30 min), and 0.25 microgram significantly reversed the subsequent hyperactivity (40-120 min). In the VTA, MN had the weakest effects, failing to reverse significantly the initial depressant effects of heroin (0-30 min), and only attenuating the subsequent hyperactivity at the highest doses. It is suggested that certain opiates act on the mesolimbic dopaminergic pathway at the level of the cell bodies in the VTA, but more critically in the N.Acc., possibly on opiate receptors postsynaptic to the dopamine neurons.
10.1016/0091-3057(85)90014-0
pubmed_121_24320
The goal of this study was to identify cocktails of drugs able to protect cultured rodent cortical neurons against increasing durations of oxygen-glucose deprivation (OGD). As expected, a cocktail composed of an NMDA and AMPA receptor antagonists and a voltage gated Ca2+ channel blocker (MK-801, CNQX and nifedipine, respectively) provided complete neuroprotection against mild OGD. Increasingly longer durations of OGD necessitated increasing the doses of MK-801 and CNQX, until these cocktails ultimately failed to provide neuroprotection against supra-lethal OGD, even at maximal drug concentrations. Surprisingly, supplementation of any of these cocktails with blockers of TRPM7 channels for increasing OGD durations was not neuroprotective, unless these blockers possessed the ability to inhibit NMDA receptors. Supplementation of the maximally effective cocktail with other NMDA receptor antagonists augmented neuroprotection, suggesting insufficient NMDAR blockade by MK-801. Substitution of MK-801 in cocktails with high concentrations of a glycine site NMDA receptor antagonist caused the greatest improvements in neuroprotection, with the more potent SM-31900 superior to L689,560. Substitution of CQNX in cocktails with AMPA receptor antagonists at high concentrations also improved neuroprotection, particularly with the combination of SYM2206 and NBQX. The most neuroprotective cocktail was thus composed of SM-31900, SYM2206, NBQX, nifedipine and the antioxidant trolox. Thus, the cumulative properties of antagonist potency and concentration in a cocktail dictate neuroprotective efficacy. The central target of supra-lethal OGD is excitotoxicity, which must be blocked to the greatest extent possible to minimize ion influx.
10.1016/j.neuint.2022.105381
pubmed_943_20161
The neonatal mammalian skeletal muscle contains both type 1 and type 3 ryanodine receptors (RyR1 and RyR3) located in the sarcoplasmic reticulum membrane. An allosteric interaction between RyR1 and dihydropyridine receptors located in the plasma membrane mediates voltage-induced Ca(2+) release (VICR) from the sarcoplasmic reticulum. RyR3, which disappears in adult muscle, is not involved in VICR, and the role of the transiently expressed RyR3 remains elusive. Here we demonstrate that RyR1 participates in both VICR and Ca(2+)-induced Ca(2+) release (CICR) and that RyR3 amplifies RyR1-mediated CICR in neonatal skeletal muscle. Confocal measurements of intracellular Ca(2+) in primary cultured mouse skeletal myotubes reveal active sites of Ca(2+) release caused by peripheral coupling between dihydropyridine receptors and RyR1. In myotubes lacking RyR3, the peripheral VICR component is unaffected, and RyR1s alone are able to support inward CICR propagation in most cells at an average speed of approximately 190 microm/s. With the co-presence of RyR1 and RyR3 in wild-type cells, unmitigated radial CICR propagates at 2,440 microm/s. Because neonatal skeletal muscle lacks a well developed transverse tubule system, the RyR3 reinforcement of CICR seems to ensure a robust, uniform, and synchronous activation of Ca(2+) release throughout the cell body. Such functional interplay between RyR1 and RyR3 can serve important roles in Ca(2+) signaling of cell differentiation and muscle contraction.
10.1074/jbc.M106944200
pubmed_86_6183
Splenic vein occlusion due to chronic pancreatitis may result in "left-sided portal hypertension," which is associated with gastric variceal hemorrhage. Intraoperative hemorrhage is also a major problem in this patient group, and it has been suggested that preoperative splenic arterial occlusion offers a means to diminish intraoperative blood loss. In order to assess the benefit of preoperative control of arterial inflow on intraoperative blood loss, we reviewed retrospectively 16 cases of chronic pancreatitis and associated splenic vein occlusion in patients who had splenectomy. There was a significant difference in estimated intraoperative blood loss in the two patient groups (P less than .05). Preoperative inflow control was obtained with a wedge balloon catheter or autologous clot embolization with an estimated mean blood loss of 1771 mL in seven patients. Nine patients had splenectomy without inflow control, with a mean estimated intraoperative blood loss of 3332 mL. The mean difference was 1560 mL. Preoperative control of splenic artery inflow can diminish intraoperative blood loss during splenectomy in the presence of splenic vein occlusion associated with chronic pancreatitis.
10.1097/00007611-199009000-00010
pubmed_265_824
The treatment aim is restoration of adequate length of the radius, adjustment of the distal radioulnar joint, alignment of the distal radius joint surface, and prevention of reflex dystrophy syndrome. Stable fractures are treated by close reduction and a cast for 3-4 weeks, depending on bone stock quality. Instable extra-articular fractures are treated by K-wiring using various methods. In case of a comminuted dorsal or palmar area, K-wiring is unstable, so additional fixation is necessary (autogeneous bone graft + external fixator + plate or cast). The external fixator alone or in combination with K-wires is the appropriate fixation method all intra- or extra-articular comminuted fractures. Palmar or dorsal plate osteosynthesis is highly recommended in palmar or dorsal rim fractures (B 3, B 2 type), whereas in C 2 to C 3 fractures additional autogeneous graft and/or K-wires or screws are necessary should be used in combination with autogeneous graft, according to the fracture pattern. Ligament injuries or luxation in the carpal row must be looked for precisely and treated according to the injury pattern.
pubmed_265_824
pubmed_190_2179
RATIONALE AND OBJECTIVES Ghrelin, an orexigenic (appetite stimulating) peptide activates binding sites in the ventral tegmental area (a structure linked with the neural reward system) allowing it to participate in reward-seeking behavior. An increasing number of studies over the past few years have demonstrated ghrelin's role in alcohol, cocaine, and nicotine abuse. However, the role of ghrelin, in opioid effects, has rarely been examined. The aim of the present study was to ascertain whether a ghrelin antagonist (JMV2959) was able to inhibit markers of morphine-induced activation of the neural reward system, namely morphine-induced increase of dopamine in the nucleus accumbens and behavioral changes in rats. METHODS We used in vivo microdialysis to determine changes of dopamine and its metabolites in the nucleus accumbens shell in rats following morphine (MO, 5, 10 mg/kg s.c.) administration with and without ghrelin antagonist pretreatment (JMV2959, 3, 6 mg/kg i.p., 20 min before MO). Induced behavioral changes were simultaneously monitored. RESULTS JMV2959 significantly and dose dependently reduced MO-induced dopamine release in the nucleus accumbens shell and affected concentration of by-products associated with dopamine metabolism: 3-methoxytyramine (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA). JMV2959 pretreatment also significantly reduced MO-induced behavioral stimulation, especially stereotyped behavior. CONCLUSIONS Ghrelin secretagogue receptors (GHS-R1A) appear to be involved in the opioid-induced changes in the mesolimbic dopaminergic system associated with the reward processing.
10.1007/s00213-014-3466-9
pubmed_33_9695
Germinal center kinases (GCKs) participate in a variety of signaling pathways needed to regulate cellular functions including apoptosis, cell proliferation, polarity and migration. Recent studies have shown that GCKs are participants in both adaptive and innate immune regulation. However, the differential activation and regulatory mechanisms of GCKs, as well as upstream and downstream signaling molecules, remain to be fully defined. It remains unresolved whether and how GCKs may cross-talk with existing signaling pathways. This review stresses the progresses in research of GCKs relevant to the immune system.
10.1038/cmi.2012.30
pubmed_10_1479
BACKGROUND The daily application of drugs, often in high doses, is a factor of stress for the infertile couple. During the last decade corifollitropin alpha has allowed a friendlier scheme comparable to traditional protocols (rFSH-HMG) results. OBJECTIVE To compare the results of corifollitropin alpha in patients with a previous cycle of IVF-ICSI with traditional scheme ovarian stimulation. MATERIALS AND METHODS Observational, retrospective cohort study type that infertile couples were included. RESULTS No significant differences in the dose used HFRS (2023U/ total ± 712 vs 636 U/total ± 307) and serum estradiol day shooting HGCr (1972 pg/dL vs 1107 ± 1152 pg/dL ± 775). A higher pregnancy rate was found corifollitropin alpha perhaps because it was a second attempt at in vitro fertilization. CONCLUSIONS Reproductive outcomes in a cycle of ovarian stimulation with corifollitropin are comparable with the results of a traditional ovarian stimulation cycle. It is important to broaden the experience of the drug indication in Mexican patients.
pubmed_10_1479
pubmed_455_5357
Having demonstrated recently that the orbitofrontal cortex is selectively involved when novel abstract visual information is encoded, we investigated whether the same orbitofrontal area would be activated during the encoding of novel human faces. The present positron emission tomography study demonstrated that area 11 in the right orbitofrontal region, which is directly linked to the medial temporal lobe, is a critical frontal area selectively activated when normal human subjects are engaged in encoding visually presented faces. Furthermore, better face recognition performance correlated with greater cerebral blood flow specifically in this orbitofrontal area.
10.1046/j.1460-9568.2003.02714.x
pubmed_176_7950
To detect genetic association with common and complex diseases, two powerful yet quite different multimarker association tests have been proposed, genomic distance-based regression (GDBR) (Wessel and Schork [2006] Am J Hum Genet 79:821–833) and kernel machine regression (KMR) (Kwee et al. [2008] Am J Hum Genet 82:386–397; Wu et al. [2010] Am J Hum Genet 86:929–942). GDBR is based on relating a multimarker similarity metric for a group of subjects to variation in their trait values, while KMR is based on nonparametric estimates of the effects of the multiple markers on the trait through a kernel function or kernel matrix. Since the two approaches are both powerful and general, but appear quite different, it is important to know their specific relationships. In this report, we show that, under the condition that there is no other covariate, there is a striking correspondence between the two approaches for a quantitative or a binary trait: if the same positive semi-definite matrix is used as the centered similarity matrix in GDBR and as the kernel matrix in KMR, the F-test statistic in GDBR and the score test statistic in KMR are equal (up to some ignorable constants). The result is based on the connections of both methods to linear or logistic (random-effects) regression models.
10.1002/gepi.20567
pubmed_982_15997
Most studies showing that autologous stem cell transplantation (ASCT) is feasible in older patients with acute myeloid leukemia (AML) referred to highly selected patients considered as eligible after complete remission (CR) achievement and bone marrow or peripheral blood stem cell (PBSC) collection. This study evaluated the feasibility of ASCT from 155 consecutive AML patients aged over 60 years (median age 72 years, range 61 - 94) programmed to receive ASCT by using PBSCs after CR achievement. Overall, 90 out of 155 patients (58%) were judged as eligible for aggressive chemotherapy and 45 (50%) achieved CR. Among these, 36 (80%) received consolidation and 32 (89% of consolidated) were monitored for PBSC mobilization. A successful collection was registered in 25/32 patients (78% of monitored). Finally, 20 patients received ASCT. Reasons for not autografting five mobilizing patients included relapse pre-ASCT, toxicity, and refusal. Median survival was 4 months for the whole patient population and 19 months for patients actually autografted. Overall, 20 out of 90 patients accrued into intensive chemotherapy (22%) and 20 out of the entire patient population (13%) underwent ASCT. It is concluded that APBSCT can result in an improvement of therapeutic results in AML of the elderly, but it is feasible in a minority of selected patients.
10.1080/10428190600624730
pubmed_348_23319
Sepsis is a major health problem. The concept that sepsis mortality is the result of an uncontrolled hyperinflammatory host response has recently been challenged. It is now widely thought that the host response to sepsis involves many, concomitant, integrated, and often antagonistic processes that involve both exaggerated inflammation and immune suppression. Several novel mediators and pathways have been shown to play a part. Moreover, evidence is accumulating that microbial virulence and bacterial load contribute to the host response and the outcome of severe infections. A complex and dynamic interaction exists between pathogens and host immune-defence mechanisms during the course of invasive infection. Some pathogens have acquired the capacity to communicate with each other and sense the host's vulnerabilities. Bidirectional signals are detectable at the critical interface between the host and microbial invaders. The outcome of this interaction determines the fate of the host at the outset of the septic process. A formidable array of innate and acquired immune defences must be breached if a pathogen is to successfully disseminate and cause severe sepsis and septic shock. This Review summarises current knowledge of microbial pathogenesis and host-pathogen interactions during sepsis and the ensuing development of potential therapeutics.
10.1016/S1473-3099(07)70265-7
pubmed_835_14475
Although single-atom catalysts (SACs) have been largely explored in lithium-sulfur (Li-S) batteries, the commonly reported nonpolar transition metal-N4 coordinations only demonstrate inferior adsorption and catalytic activity toward shuttled lithium polysulfides (LiPSs). Herein, single Fe atoms with asymmetric coordination configurations of Fe-N3C2-C were precisely designed and synthesized as efficient immobilizer and catalyst for LiPSs. The experimental and theoretical results elucidate that the asymmetrically coordinated Fe-N3C2-C moieties not only enhance the LiPSs anchoring capability by the formation of extra π-bonds originating from S p orbital and Fe d/d orbital hybridization but also boost the redox kinetics of LiPSs with reduced Li2S precipitation/decomposition barrier, leading to suppressed shuttle effect. Consequently, the Li-S batteries assembled with Fe-N3C2-C exhibit high areal capacity and cycling stability even under high sulfur loading and lean electrolyte conditions. This work highlights the important role of coordination symmetry of SACs for promoting the practical application of Li-S batteries.
10.1021/acs.nanolett.2c02183
pubmed_1015_6177
Using the binocular fixation pattern (BFP) and the visually evoked potential (VEP), thirteen amblyopic patients with comitant, non-accommodative esotropia with an angle range up to 30 delta were studied before and during occlusion therapy. A graded BFP with a stronger preferred fixation could be used to diagnose amblyopia. The BFP, however, showed no significant change with therapy despite improvement in acuity. In contrast, the VEP amplitudes, initially reduced in amblyopia, increased significantly as the vision responded to patching. The VEP was useful in diagnosing strabismic amblyopia and giving a predictive range of acuities.
10.1016/s0161-6420(80)35095-1
pubmed_5_6772
BACKGROUND While music/music therapy does not represent a treatment of dementia, its use is based on a possible beneficial effect on symptoms including social, emotional and cognitive skills and for decreasing behavioral problems of individuals with dementias. Thus, there are clear implications for patients' and caregivers' quality of life. However, quantification and documentation of the evidence of this effect is necessary. Professional music therapists are accountable for providing efficient, beneficial treatment. Further, music therapists are responsible for assessing, designing and implementing music therapy treatments, monitoring client progress, and reformulating their practice according to data collected and new advancements in the field. If they wait until sufficient valid, empirical data on all aspects of a disability or music response are available before attempting to design a therapy session, they may well reach retirement age before even one client can be served. On the other hand, promulgating the efficacy of music therapy in general, or of specific music therapy techniques, in the absence of any substantiation other than intuition or tradition borders on professional recklessness. OBJECTIVES To gather and evaluate the evidence for the effectiveness of music therapy for dementia symptoms. SEARCH STRATEGY All available sources of references were searched for randomised controlled trials of music therapy used as an intervention in dementia. The search terms included 'controlled trial or study, music*, therapy, dement*, Alzheimer*, cognitive impairment.' SELECTION CRITERIA The reviewers assessed the methodological quality of the studies available for inclusion. The criteria used are presence and adequacy of a control condition, independent assessment of patients' performance (ie standardized ratings carried out by a person other than the music therapist) and the number of participants (no fewer than three). DATA COLLECTION AND ANALYSIS No randomised controlled trials, or trials with quantitative data suitable for analysis were found. MAIN RESULTS The research into music therapy to date has lacked methodological design rigour. However, the research evidence available provides sufficient grounds on which to justify further investigations into the use of music therapy in dementia patients. In this context, the reviewers discuss some of the issues and research from the studies that were considered for inclusion. REVIEWER'S CONCLUSIONS This review was not able to identify reliable empirical evidence on which to justify the use of music therapy as a treatment for dementia. However, the evidence available suggests that music therapy may be beneficial in treating or managing dementia symptoms, and the predominant conclusion of this review is the highlighting of the need for better designed studies of the intervention.
10.1002/14651858.CD001121
pubmed_277_3324
Activation of the macrophage cell line RAW 264.7 with lipopolysaccharide (LPS) and gamma interferon (IFN-gamma) induces the expression of gene products involved in host defense, among them type 2 nitric oxide synthase. Treatment of cells with 15-deoxy-Delta(12,14)-prostaglandin J(2) (15dPGJ(2)) inhibited the LPS- and IFN-gamma-dependent synthesis of NO, a process that was not antagonized by similar concentrations of prostaglandin J(2), prostaglandin E(2), or rosiglitazone, a peroxisomal proliferator-activated receptor gamma ligand. Incubation of activated macrophages with 15dPGJ(2) inhibited the degradation of IkappaBalpha and IkappaBbeta and increased their levels in the nuclei. NF-kappaB activity, as well as the transcription of NF-kappaB-dependent genes, such as those encoding type 2 nitric oxide synthase and cyclooxygenase 2, was impaired under these conditions. Analysis of the steps leading to IkappaB phosphorylation showed an inhibition of IkappaB kinase by 15dPGJ(2) in cells treated with LPS and IFN-gamma, resulting in an impaired phosphorylation of IkappaBalpha, at least in the serine 32 residue required for targeting and degradation of this protein. Incubation of partially purified activated IkappaB kinase with 2 microM 15dPGJ(2) reduced by 83% the phosphorylation in serine 32 of IkappaBalpha, suggesting that this prostaglandin exerts direct inhibitory effects on the activity of the IkappaB kinase complex. These results show rapid actions of 15dPGJ(2), independent of peroxisomal proliferator receptor gamma activation, in macrophages challenged with low doses of LPS and IFN-gamma.
10.1128/MCB.20.5.1692-1698.2000
pubmed_235_6294
Tuberculosis (TB) is the leading cause of death among HIV-1-infected individuals and Mycobacterium tuberculosis (Mtb) co-infection is an early precipitate to AIDS. We aimed to determine whether Mtb strains differentially modulate cellular susceptibility to HIV-1 infection (cis- and trans-infection), via surface receptor interaction by their cell envelope lipids. Total lipids from pathogenic (lineage 4 Mtb H37Rv, CDC1551 and lineage 2 Mtb HN878, EU127) and non-pathogenic (Mycobacterium bovis BCG and Mycobacterium smegmatis) Mycobacterium strains were integrated into liposomes mimicking the lipid distribution and antigen accessibility of the mycobacterial cell wall. The resulting liposomes were tested for modulating in vitro HIV-1 cis- and trans-infection of TZM-bl cells using single-cycle infectious virus particles. Mtb glycolipids did not affect HIV-1 direct infection however, trans-infection of both R5 and X4 tropic HIV-1 strains were impaired in the presence of glycolipids from M. bovis, Mtb H37Rv and Mtb EU127 strains when using Raji-DC-SIGN cells or immature and mature dendritic cells (DCs) to capture virus. SL1, PDIM and TDM lipids were identified to be involved in DC-SIGN recognition and impairment of HIV-1 trans-infection. These findings indicate that variant strains of Mtb have differential effect on HIV-1 trans-infection with the potential to influence HIV-1 disease course in co-infected individuals.
10.3390/ijms22041945
pubmed_230_129
To understand whether a low-frequency pulsed electromagnetic field (EMF) could help cartilage tissue repair in the scope of tissue engineering, we tested how EMF affected collagen gel properties and the behaviors of chondrocyte cells embedded in collagen constructs. Collagen gel and primary chondrocytes embedded in collagen were exposed to EMF for 24 h. Gel and cells that were not exposed to EMF served as controls. Collagen gel exposed to EMF was more hydrophobic and less susceptible to enzymatic degradation (both p < 0.05) than control. Three weeks after EMF exposure, chondrocytes showed higher proliferation and lower glycosaminoglycan (GAG) production (both p < 0.05) than control. By the end of the third week, aggrecan, type I, II, and X collagen mRNA expressions in the EMF group were 1.8 times higher (p < 0.05), except for type II collagen) than control. The increase in gene expression did not show up in aggrecan histological staining and type II and type X collagen immunohistochemical staining. Cells from both groups kept a normal polygonal shape through out the test period. Our results suggested that one-time EMF exposure could promote collagen-embedded chondrocytes proliferation and their gene expressions. It also promoted short-term (week 1) GAG production and lacuna formation. No apparent GAG and type II collagen production was seen in histological staining three weeks after the EMF exposure.
10.1002/jbm.a.32405
pubmed_548_24258
Few methods for noninvasive assessment of arterial stiffness and endothelial dysfunction in porcine models are available. The aim of this study was to evaluate methods for assessment of arterial stiffness and endothelial dysfunction in anesthetized Göttingen minipigs. Pulse-wave velocity (PWV) was assessed in male Göttingen minipigs (n = 8; age approximately 60 wk) by using applanation tonometry of the carotid and femoral arteries. In addition, flow-mediated vasodilation (FMD) was assessed by using vascular ultrasonography of the brachial artery to evaluate endothelial dysfunction. To evaluate the reproducibility of the methods, minipigs were anesthetized by intravenous infusion of ketamine and midazolam and examined every other day for a total of 3 trials. Neither examination day nor systolic, diastolic, or mean arterial blood pressure statistically influenced PWV or FMD. The median interexamination coefficient of variation was 17% for PWV and 59% for FMD. Measured values of PWV corresponded largely to those in clinically healthy humans, but FMD values were lower than expected for lean, young animals. Although the ketamine-midazolam anesthesia we used has been associated with minor hemodynamic effects in vivo, in vitro studies suggest that both drugs are vasodilatory. Therefore anesthesia might have influenced the endothelial response, contributing to the modest FMD response and the concurrent high coefficients of variation that we noted. We conclude that PWV—but not FMD—showed acceptable interexamination variation for its potential application in porcine models.
pubmed_548_24258
pubmed_947_18635
BACKGROUND A restrictive use of episiotomy was recommended by the obstetric society in China, but limited information on the epidemiology and the effects of restrictive use of episiotomy on maternal and fetal outcomes have been published. METHODS The China Labor and Delivery Survey is a cross-sectional investigation with a cluster random sampling scheme in 2015-2016 with the aim to describe detailed epidemiology of labor and delivery in China. We calculated the episiotomy rate by parity using the survey data. Associated factors of episiotomy were selected using mixed models with a random effect for the hospital-level clustering. Logistic regression models were fitted to examine the effects of mediolateral episiotomy on maternal and neonatal outcomes among the propensity score-matched women. FINDINGS The episiotomy rate among vaginal births was 41·7% [95% confidence interval (CI): 40·1% - 43·2%] in nulliparae and 21·5% (95% CI: 19·4% - 23·5%) in multiparae in China. Associated factors of episiotomy included prepregnancy BMI, maternal diseases, and obstetric factors. More than half of episiotomies in nulliparae and one-fourth in multiparae had no indications. Mediolateral episiotomy without indicators increased the risk of 3rd or 4th degree perineal laceration [odds ratio (OR) =2·64, 95% CI: 1·08-6·48)] in nulliparae without neonatal benefits. INTERPRETATION Episiotomy was performed more than medically necessary in China. Mediolateral episiotomy without indications more than doubled the risk of 3rd and 4th degree perineal laceration in nulliparae without neonatal benefits. FUNDING National Natural Science Foundation of China and Shanghai Health Commission Programme.
10.1016/j.lanwpc.2021.100345
pubmed_979_2901
Cigarette smoking is a well-known risk factor for atherosclerotic disorders. Several authors have suggested that platelet aggregability is important in smoking-induced vascular injury. When platelet-rich plasma is stirred at 37 degrees C in the absence of chemical stimulants, small aggregates of platelets may be formed, but it was difficult to detect small aggregates by conventional aggregometer using optical density. Recent technological advances have made it possible to detect small aggregates by using a newly developed assay system that employs laser light scattering. In the present study, we attempted to measure platelet aggregation by this method, using laser light scattering in 54 nonsmoking healthy males and 51 healthy male habitual smokers who were age matched. In smokers, blood was obtained after 10 hours of smoking abstinence. No significant difference in platelet aggregation was induced by 1 microM or 5 microM of ADP between smokers and nonsmokers. In smokers, plasma fibrinogen levels and the number of small aggregates formed in the absence of chemical stimulants was significantly higher than in nonsmokers. Small aggregates formed in the absence of stimulants correlated positively with the concentrations of von Willebrand factor (vWF) antigen (r=0.2654, p<0.01) and of fibrinogen (r=0.2834, p<0.01). The formation of these small aggregates was inhibited by monoclonal antibody against GPIIb/IIIa blocking fibrinogen binding to GPIIb/IIIa but not inhibited at all by monoclonal antibody against GPIb blocking vWF binding to GPIb. From these results, enhanced platelet aggregability in smokers was confirmed, and it was suggested that GPIIb/IIIa is concerned in platelet spontaneous aggregation, although vWF may not directly influence on the platelet spontaneous aggregation. Since the mechanism of spontaneous aggregation and the effect of increased spontaneous aggregability on the progression of atherosclerosis remains unclear, further study was considered necessary.
10.1016/s0049-3848(98)00184-4
pubmed_388_4366
Radiographic and bone mineral (BM) data were collected over a three-year period on 195 patients with chronic renal failure. Most women maintained BM on dyalysis, whereas 44% of the men lost BM (p less than 0.05). Following transplantation, 86% of the patients either maintained or restored BM. After parathyroidectomy, only half of the women and 34% of the men gained BM. Normal radiographs may be associated with low BM values, but there is a correlation between decreasing BM and increasing renal osteodystrophy in women (p less than 0.05).
10.1148/122.3.643
pubmed_465_8255
Rats were reared on a standard diet up to the age of 6 weeks when they were divided into two groups. One was fed on a diet containing 14% protein and the other on a diet with only 1.5% protein. The size of the various fibre types of the EDL muscle of both groups was assessed at 6 and 25 weeks of age. All the fibre types of protein-deprived rats were smaller compared to the age-matched controls, the difference being most evident in the 2B fibres. In the protein-deprived rats the 2B fibres atrophied while the type 1 and type 2A fibres simply failed to grow. Histochemical and ultrastructural examination revealed a marked reduction of the subsarcolemmal mitochondria after prolonged protein deprivation; normally large accumulations of mitochondria are seen preferentially in type 2A fibres.
10.1016/0022-510x(83)90046-1
pubmed_118_17491
Background. Several studies have described but not formally tested discrepancies between subjective and objective measures of sleep. Study Objectives. To test the hypothesis that patients with bipolar disorder display a systematic bias to underestimate sleep duration and overestimate sleep latency. Methods. Actimetry was used to assess sleep latency and duration in 49 euthymic participants (bipolar = 21; healthy controls = 28) for 5-7 days. Participants simultaneously recorded estimated sleep duration and sleep latency on a daily basis via an online sleep diary. Group differences in the discrepancy between subjective and objective parameters were calculated using t-tests and corrected for multiple comparisons. Results. Patients with bipolar disorder significantly underestimated their sleep duration but did not overestimate their sleep latency compared to healthy controls. Conclusions. Studies utilizing diaries or questionnaires alone in patients with bipolar disorders may systematically underestimate sleep duration compared to healthy controls. The additional use of objective assessment methods such as actimetry is advisable.
10.1155/2016/4031535
pubmed_85_13732
The spectrum of two-dimensional (2D) and layered materials 'beyond graphene' offers a remarkable platform to study new phenomena in condensed matter physics. Among these materials, layered hexagonal boron nitride (hBN), with its wide bandgap energy (∼5.0-6.0 eV), has clearly established that 2D nitrides are key to advancing 2D devices. A gap, however, remains between the theoretical prediction of 2D nitrides 'beyond hBN' and experimental realization of such structures. Here we demonstrate the synthesis of 2D gallium nitride (GaN) via a migration-enhanced encapsulated growth (MEEG) technique utilizing epitaxial graphene. We theoretically predict and experimentally validate that the atomic structure of 2D GaN grown via MEEG is notably different from reported theory. Moreover, we establish that graphene plays a critical role in stabilizing the direct-bandgap (nearly 5.0 eV), 2D buckled structure. Our results provide a foundation for discovery and stabilization of 2D nitrides that are difficult to prepare via traditional synthesis.
10.1038/nmat4742
pubmed_1141_20391
Two females, Denean Worms and Brenda Hughes, were murdered in separate events in Cranbrook, British Columbia in 1984 within three months of each other. Terrence Wayne Burlingham was found guilty of both murders and he appealed. The Supreme Court of Canada granted Burlingham a new trial in the Worms case, but no evidence from Burlingham's confession nor the murder weapon could be used. The Crown counsel requested an evaluation of the two murders to determine if they were committed by the same person. The analyses of those murders revealed that they were linked by a personal "signature" of the killer. The murder cases reported here demonstrate a control-oriented signature. The killer used a .410 shotgun as his method of control and death, engaged in overkill of each victim by shooting them twice in the head, and left the victims in sexually degrading positions. Another signature feature was the absence of typical wounds to the victims which would be expected from a serial sex offender. All of these characteristics, in combination, accounted for this killer's personal expression.
pubmed_1141_20391
pubmed_269_14054
Paralytic shellfish toxins (PSTs) are a large group of biotoxins that cause paralytic shellfish poisoning. Their appearance in natural waters and their ingestion by aquatic species have a huge socio-economic impact, whereby their monitoring is of the upmost relevance to minimize the consequences. For earlier detection and faster response/action by stakeholders, validation of adjusted analytical methods, particularly for lower concentration levels, is important. This work proposes a derived High-Performance Liquid Chromatography method, with fluorescence detection (HPLC-FLD). The main differences from the official method are the size of the HPLC column and the gradient elution conditions. It covers the current eleven certified reference materials (CRM) available on the market, including the most recent-C3,4. This first calibration report for C3,4 suggests limits of detection (LOD) and limits of quantification (LOQ) of 6 nM and 19 nM (~5 µg STX.2HCl eqv./kg and 17 µg STX.2HCl eqv./kg), respectively. For the remaining CRM, LODs ranged between 3 and 28 nM (~0.9 and 127 µg STX.2HCl eqv./kg), while LOQs varied between 11 and 94 nM (~3 and 409 µg STX.2HCl eqv./kg, considering toxicity equivalency factors (TEFs) reported by EFSA).
10.3390/toxins14030179
pubmed_795_2813
Although the liver has been known for its enormous regenerative capacity, little is known about the mechanisms responsible for such regeneration.To provide evidence for the existence of liver stem cell, using FACS and single cell-based assays, cells with multi-lineage differentiation potential and self-renewal capability have been prospectively identified. These cells could be clonally propagated in culture where they continuously produced hepatocytes and cholangiocytes as descendants while maintaining primitive stem cells. When the cells clonally expanded in vitro were transplanted into mouse, they morphologically and functionally differentiated into hepatocytes and cholangiocytes. Furthermore, these cells differentiated into pancreatic acinar cells or intestinal epithelial cells upon transplantation into pancreas or duodenal wall. Manipulation of self-renewing liver stem cells may provide new insight into therapies for diseases of the digestive system.
10.1016/s1084952102001349
pubmed_311_18430
Endothelial cells are vital to blood coagulation and maintain whole body hemostasis. Binding of endothelial cells to endothelial protein C receptor (EPCR) and thrombomodulin (TM) is essential to the formation of activated protein C (APC), one of the key factors regulating blood coagulation. In our study, we showed that resistin, an adipocyte hormone, suppresses thrombin-induced protein C activation in endothelial cells. Resistin treatment results in a reduction in EPCR expression, but not TM. Mechanistically, we demonstrate that resistin induces expression of the nuclear transcription factor SP-1, which could lead to downregulation of EPCR. Both inhibition and silencing of SP1 protein abolishes abnormal APC generation induced by resistin. Collectively, our data support a new role of resistin in disturbing APC formation.
10.1016/j.biopha.2018.09.160
pubmed_672_6004
The authors report MR findings in 139 patients with 159 cerebral vascular malformations (36 arteriovenous malformations, 25 venous angiomas and 98 cavernous angiomas). Morphological aspects and hemodynamic findings due to rapid and slow flow are analysed. MR is able to differentiate the various type of lesions and permits the visualization of angiographically occult vascular malformations. In the case of cavernous angiomas MR information may not be sufficient for an absolute diagnosis because of differential diagnostic problems; correlation with the clinical history, CT and angiographic findings and follow-up MR study are certain to be necessary to increase specificity. Usually it is possible to distinguish histopathological components of the lesion and perilesional modifications in the cerebral parenchyma.
pubmed_672_6004
pubmed_1061_24317
Transcatheter therapies to treat mitral regurgitation are rapidly developing. Currently, there are several devices commercially available to treat mitral regurgitation. The underlying cause of mitral regurgitation and specific anatomical aspects of the mitral valve and surrounding structures are considered when patients with symptomatic severe mitral regurgitation for transcatheter mitral valve therapies are selected. Multimodality imaging plays an important central role in the selection of patients, providing information about the mechanism of mitral regurgitation, the anatomy of the mitral valve and spatial relationships with the coronary sinus, the circumflex coronary artery and left ventricular outflow tract and to predict the procedural outcomes. During the transcatheter procedure, transesophageal echocardiography and fluoroscopy are key for monitoring the procedural steps to maximize the outcomes and minimize the complications. This paper provides a comprehensive review of the most important aspects to visualize in order to appropriately select patients for transcatheter mitral valve repair and replacement and to guide the procedure for the different transcatheter devices.
10.1016/j.jcmg.2019.03.036
pubmed_205_21156
We examined a young man who had a benign giant cell granuloma of the maxilla, which we subsequently diagnosed as a brown tumor associated with hyperparathyroidism. During surgery for the granuloma, the patient developed severe hypertension and was discovered to have an extra-adrenal pheochromocytoma. Oncogene and calcitonin testing for medullary carcinoma of the thyroid was negative. Therefore, despite the presence of both pheochromocytoma and hyperparathyroidism, we concluded that this patient did not have multiple endocrine neoplasia type 2a.
pubmed_205_21156
pubmed_135_24100
The trend of feeding dogs and cats with raw pet food claiming health benefits poses health concerns due to the occurrence of pathogenic bacteria. High pressure processing (HPP) allows the non-thermal inactivation of microorganisms, preserving the nutritional characteristics with minimal impact on organoleptic traits of food. The present study aimed to evaluate and model the effect of HPP application (450-750 MPa for 0-7 min) on the inactivation of Salmonella, endogenous microbiota and colour of raw pet food formulated with different concentrations of lactic acid (0-7.2 g/kg) as natural antimicrobial. Additionally, the effect of a subsequent frozen storage of pressurized product was assessed. Salmonella inactivation ranged between 1 and 9 log, depending on the combination of conditions. According to the polynomial model obtained, the effect of pressure was linear, while a quadratic term was also included for holding time (depicting the occurrence of a resistant tail at ca. 4-6 min). The effect of lactic acid was dependent on the pressure level, being most relevant for treatments below 600 MPa. Frozen storage after HPP prevented the pathogen recovery and caused a further Salmonella inactivation enhanced by lactic acid in most of the treatments. Endogenous microbial groups were significantly reduced by HPP to below the detection level in several conditions. In general, little effect of HPP on the instrumental colour parameters was observed, except for a slight increase in lightness, which was hardly appreciable from visual observation. High pressure processing emerges as a relevant technology for the control of Salmonella spp. and to manage the microbiological safety of raw pet food. The mathematical model can be used as decision support tool to design safer raw pet food, while keeping the desired freshness appearance of the products.
10.1016/j.fm.2022.104139
pubmed_778_8289
The relationship between numbers of carrot weevil, Listronotus oregonensis (LeConte), oviposition scars and parsley fresh weight and plant mortality was measured in research plots during 1999 and 2000. Fresh weight was measured in one to two cuttings of parsley planted on two planting dates. The average weight declined with increasing numbers of oviposition scars in the later planting in 1999. Compensatory growth in surviving plants may reduce this effect. Plant mortality increased as number of oviposition scars per plant increased in the second planting in both years and in the first cutting of the first planting in 2000. One oviposition scar per plant is sufficient to result in significant reduction in fresh weight per plant. In commercial parsley fields, the relationship between fresh weight of parsley per 30-cm row section of parsley was best described as a linear function of the proportion of plants with root feeding. Economic damage to parsley that is equivalent to the cost of controlling carrot weevil was estimated to result from approximately 1% of plants with root damage. Based upon this estimated economic injury level, we suggest an action threshold of 1% of plants containing carrot weevil oviposition scars earlier in the growing season when controls could be applied to prevent the damage.
10.1603/0022-0493-98.4.1213
pubmed_926_11620
BACKGROUND The treatment of recurrent esophageal stricture secondary to the ingestion of a caustic agent is an arduous task. Self-expanding esophageal stents may be an alternative to repeated endoscopic esophageal dilations. CASE REPORT We present the case of a two-year-old male with a severe and long esophageal stricture successfully treated by the combination of dilations and stent placement. After five months of serial pneumatic dilations, three self-expanding nitinol stents internally coated with silicone were introduced through a gastrostomy, covering the entire esophagus. The procedure was performed under endoscopic and radiological guidance. Three months later, the treatment was repeated with a single stent. A new stenosis in the proximal esophagus required surgical resection, and anastomosis followed by two pneumatic dilations for five months resulted in longer intervals where the patient was asymptomatic. DISCUSSION The results obtained were satisfactory, allowing the patient to conserve and use his own esophagus. However, this is a unique case and the optimal maintenance time and withdrawal time of the stent must be determined.
10.17235/reed.2017.4959/2017
pubmed_715_19961
The structures and energetics of Li(6) (+), Li(6) (-) and three isomers of Li(6) are investigated using the coupled-cluster singles, doubles and perturbative triples [CCSD(T)] method with valence and core-valence correlation consistent basis sets of double- to quadruple-zeta quality (cc-pVXZ and cc-pCVXZ, where X=D-Q). These results are compared with qualitatively different predictions by less reliable methods. Our results conclusively show that the D(4h) isomer is the global minimum structure for Li(6). It is energetically favored over the C(5v) and D(3h) structures by about 5.1 and 7.1 kcal mol(-1), respectively, after the inclusion of the zero-point vibrational energy (ZPVE) correction. Our most accurate total atomization energies are 123.2, 117.6, and 115.7 kcal mol(-1) for the D(4h), C(5v), and D(3h) isomers, respectively. Comparison of experimental optical absorption spectra with our computed electronic spectra also indicate that the D(4h) isomer is indeed the most stable structure. The cation, anion, and some higher spin states are investigated using the less expensive cc-pCVDZ basis set. Adiabatic ionization energies and electron affinities are reported and compared with experimental values. Predictions of molecular properties are found to be sensitive to the basis set used and to the treatment of electron correlation.
10.1063/1.1846671
pubmed_163_7718
This paper presents a fully automatic method for multi-organ segmentation from 3D abdominal CT volumes. Firstly, spines and ribs are removed by exponential transformation and binarization to reduce the disturbance to subsequent segmentation. Then, a Local Linear Embedding (LLE)-based graph partitioning approach is employed to perform initial segmentation for liver, spleen, and bilateral kidneys simultaneously, and a novel segmentation refinement scheme is applied composed of hybrid intensity model, 3D Chan-Vese model, and histogram equalization-based organ separation algorithm. Finally, a pseudo-3D bottleneck detection algorithm is introduced for boundary correction. The proposed method does not require heavy training or registration process and is capable of dealing with shape and location variations as well as the weak boundaries of target organs. Experiments on XHCSU20 database show the proposed method is competitive with state-of-the-art methods with Dice similarity coefficients of 95.9%, 95.1%, 94.7%, and 94.5%, Jaccard indices of 92.2%, 90.8%, 90.0%, and 89.5%, and average symmetric surface distances of 1.1 mm, 1.0 mm, 0.9 mm and 1.1 mm, for liver, spleen, left and right kidneys, respectively, and the average running time is around 6 min for a CT volume. The accuracy, precision, recall, and specificity also maintain high values for each of the four organs. Moreover, experiments on SLIVER07 dataset prove its high efficiency and accuracy on liver-only segmentation.
10.1016/j.compbiomed.2021.105030
pubmed_101_1539
(1) Background: During the COVID-19 pandemic, shortages in the supply of personal protective equipment (PPE) have become apparent. The idea of using commonly available full-face diving (FFD) masks as a temporary solution was quickly spread across social media. However, it was unknown whether an FFD mask would considerably impair complex surgical tasks. Thus, we aimed to assess laparoscopic surgical performance while wearing an FFD mask as PPE. (2) Methods: In a randomized-controlled cross-over trial, 40 laparoscopically naive medical students performed laparoscopic procedures while wearing an FFD mask with ad hoc 3D-printed connections to heat and moisture exchange (HME) filters vs. wearing a common surgical face mask. The performance was evaluated using global and specific Objective Structured Assessment of Technical Skills (OSATS) checklists for suturing and cholecystectomy. (3) Results: For the laparoscopic cholecystectomy, both global OSATS scores and specific OSATS scores for the quality of procedure were similar (Group 1: 25 ± 4.3 and 45.7 ± 12.9, p = 0.485, vs. Group 2: 24.1 ± 3.7 and 43.3 ± 7.6, p = 0.485). For the laparoscopic suturing task, the FFD mask group needed similar times to the surgical mask group (3009 ± 1694 s vs. 2443 ± 949 s; p = 0.200). Some participants reported impaired verbal communication while wearing the FFD mask, as it muffled the sound of speech, as well as discomfort in breathing. (4) Conclusions: FFD masks do not affect the quality of laparoscopic surgical performance, despite being uncomfortable, and may therefore be used as a substitute for conventional PPE in times of shortage-i.e., the global COVID-19 pandemic.
10.3390/jcm10030550
pubmed_1036_10735
The European Society of Hypertension and European Society of Cardiology guidelines published in 2007 include recommendations for the treatment of arterial hypertension (HT) in special situations. Such special situations include elderly patients, diabetes mellitus, cerebrovascular disease, cardiovascular disease, renal disease, HT in women, metabolic syndrome, refractory HT, hypertensive emergencies, and malignant HT. The aim of these guidelines is primarily educational rather than prescriptive. Each section of the guidelines includes a series of recommendations that attempt to offer guidance on the best approach in this type of patients. We summarize the recommendations made in each section of these guidelines.
pubmed_1036_10735
pubmed_815_16856
BACKGROUND Retrobulbar anesthesia is considered an effective method of obtaining anesthesia and akinesia in eye surgery. It can give rise to serious complications, however, and these complications could be considerably reduced with peribulbar anesthesia. METHODS After using peribulbar anesthesia for 2 years in surgical treatment of the anterior segment, the authors began a study to test its efficacy in posterior segment surgery. Retinal and vitreoretinal surgery with the peribulbar anesthesia technique were performed in 32 consecutive patients. RESULTS In all cases anesthesia was complete with one preoperative block. In 2 patients, however, completion of akinesia required a supplemental 2- to 3-cc injection of the anesthetic solution. Surgery was performed with preoperative block only in 31 cases. In the remaining case, a supplemental peribulbar injection of the anesthetic solution was given intraoperatively for pain. In 5 cases (15%) pain at the end of surgery from conjunctiva was controlled by anesthetic drops. CONCLUSION It is recommended that this method be used only when the duration of the operation is expected to be brief.
10.1097/00006982-199414030-00016
pubmed_218_22990
Prenatal diagnosis of truncus arteriosus with two-dimensional sonography requires expertise in fetal echocardiography. Indeed, truncus arteriosus shares with tetralogy of Fallot and pulmonary atresia with a ventricular septal defect (VSD) the sonographic finding of a single arterial trunk overriding a VSD. The diagnosis of truncus arteriosus can be confirmed when either the main pulmonary artery or its branches are visualized arising from the truncus itself. This requires sequential examination of multiple scanning planes and a process of mental reconstruction of their spatial relationships. The advantage of multiplanar imaging in three-dimensional and four-dimensional ultrasonography is that it allows for the simultaneous visualization of three orthogonal anatomic planes, which can be very important in diagnosing cardiac abnormalities. We report, first, a case of truncus arteriosus diagnosed in utero where the multiplanar display modality provided important insight into the differential diagnosis of this conotruncal anomaly, and then, review the diagnosis of truncus arteriosus on ultrasound.
10.3109/14767050903108206
pubmed_419_25696
PURPOSE A resin-bonded bridge (RBB) is a minimally invasive prosthetic treatment option for intact adjacent teeth. However, it is contentious as to whether the mesial or distal adjacent tooth should be used as an abutment. This study aimed to investigate the potential of finite element analysis (FEA) for the selection of abutment teeth and the determination of the optimal design for anterior cantilever RBBs. METHODS Three types of RBBs were designed to simulate loss of the maxillary left lateral incisor. The fixed-fixed RBB (FF-RBB) had one retainer each for the left central incisor and canine. Distal- and mesial-cantilever RBBs (D-CRBB and M-CRBB) had a single retainer on the central incisor and canine, respectively. Three-dimensional models for FEA were generated from computed tomography slices and dental casts. FEA was performed for each RBB to evaluate stresses in the intercuspal, protrusive, and lateral mandibular positions. RESULTS The maximum principal stresses on the bridges in the intercuspal position were 141.9 MPa, 93.6 MPa, and 45.7 MPa, for the FF-RBB, D-CRBB, and M-CRBB, respectively. The stress in the D-CRBB position was greater than in the M-CRBB position in the intercuspal, protrusive, and lateral mandibular positions. CONCLUSIONS Based on the results, M-CRBB on the canine had a higher clinical performance than D-CRBB on the central incisor. FEA was useful for determining the optimal design of RBB for each patient.
10.2186/jpr.JPR_D_22_00103