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pubmed_1092_23761
OBJECTIVES To analyze quality of life in people with symptomatic spine osteoarthritis (OA) using the results of a cross-sectional, nationwide survey. MATERIALS AND METHODS This study used data from the Fifth Korean National Health and Nutrition Examination Survey (KNHANES V-5; 2010-2012). After excluding ineligible subjects, the total number of subjects in the study was 8,963, including 4,091 males and 4,872 females. All participants reported disabilities related to spine OA. Plain radiographs of the spine were taken for all participants. RESULTS Age, sex, smoking, drinking, education, and income level were significantly related to spine OA morbidity (P<0.05). OA morbidity was significantly higher in female ex-smokers (OR; 2.94, P<0.05). Quality of life (EQ-5D: L1~5) was significantly compromised in the group with spine OA compared to the group without spine OA (P<0.05). Overall, LQ 1, 2, 3, 4, and 5 domain scores were significantly higher in the group with spine OA (P<0.05). In the group with spine OA, quality of life was reduced on more than three questions for 34.3% of the group (EQ-5D: grade≥2); on two questions, for 18.5% of the group; and on one question, for 11.1% of the group. Mental stress, melancholy, and suicidal thinking were also more common in the group with spine OA (P<0.05). The group with radiographic spine OA but without symptoms did not have compromised EQ-5D scores, whereas the group with radiographic OA and symptoms showed a significantly reduced quality of life. CONCLUSIONS Quality of life was significantly reduced in the group with symptomatic spine OA in a large cross-sectional analysis. Physicians should consider quality of life in the treatment of patients with spine OA.
10.1371/journal.pone.0151315
pubmed_489_22197
This study investigated the humoral immunization of Astragalus polysaccharide (APS) against H9N2 avian influenza virus (H9N2 AIV) infection in chickens.The effects of APS treatment on H9N2 infection was evaluated by an MTT [3(4, 5-dimethylthiazol-2-yl)-2, 3-diphenyl tetrazolium bromide] assay and analysis of MHC and cytokine mRNA expression. The effect on lymphocyte and serum antibody titers in vivo was also investigated. IL-4, IL-6, IL-10, LITAF, IL-12 and antibody titers to H9N2 AIV were enhanced in the first week after APS treatment. The results indicated that APS treatment reduces H9N2 AIV replication and promotes early humoral immune responses in young chickens.
10.1186/2049-1891-4-22
pubmed_1084_9115
Our understanding of hereditary hearing loss has greatly improved since the discovery of the first human deafness gene. These discoveries have only accelerated due to the great strides in DNA sequencing technology since the completion of the human genome project. Here, we review the immense impact that these developments have had in both deafness research and clinical arenas. We review commonly used genomic technologies as well as the application of these technologies to the genetic diagnosis of hereditary hearing loss and to the discovery of novel deafness genes.
10.1016/j.heares.2011.10.001
pubmed_1042_8950
Differential reinforcement of other behavior (DRO) is a procedure often used to decrease problem behavior, but the processes responsible for behavior reduction are not well understood. This study assessed whether adventitious reinforcement of other behavior contributes to DRO effectiveness when, relative to previous research, DRO exposure is prolonged. Two response options were presented on a computer and target responding was reinforced on a variable-ratio schedule. Response rates were then compared during DRO versus yoked variable-time or extinction probes. Across 2 experiments, DRO decreased target responding and increased other responding more than control conditions. However, increases in other responding did not usually maintain despite target responding remaining at low levels. DRO might adventitiously reinforce other responses transiently but the decreases in target behavior could not be entirely explained by adventitious reinforcement of the other response. Instead, reductions in target responding likely depend on the discriminability of the DRO contingency.
10.1002/jaba.697
pubmed_377_7576
BACKGROUND Recent studies have suggested that higher serum cholesterol may be associated with lower occurrence of Parkinson's disease (PD). This study is to test the hypothesis that higher serum cholesterol correlates with slower PD progression. METHODS Baseline non-fasting serum total cholesterol was measured in 774 of the 800 subjects with early PD enrolled between 1987 and 1988 in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) trial. Participants were followed for up to two years, with clinical disability requiring levodopa therapy as the primary endpoint. Hazard ratios (HRs) and 95% confidence intervals (CI) were determined for increasing serum cholesterol concentration (in quintiles) for clinical disability requiring levodopa therapy, after adjusting for confounders. At baseline, only nine subjects reported use of cholesterol-lowering agents (two with statins). RESULTS The overall mean cholesterol level was 216 mg/dL (range 100-355). The HR of progressing to the primary endpoint decreased with increasing serum cholesterol concentrations. Compared to the lowest quintile, the HRs (95%CI), for each higher quintile (in ascending order) are 0.83 (0.59-1.16); 0.86 (0.61-1.20); 0.84 (0.60-1.18); and 0.75 (0.52-1.09). The HR for one standard deviation (SD) increase = 0.90 [(0.80-1.01), p for trend = 0.09]. This trend was found in males (HR per SD = 0.88 [(0.77-1.00), p for trend = 0.05], but not in females [HR = 1.03 (0.81-1.32)]. CONCLUSIONS This secondary analysis of the DATATOP trial provides preliminary evidence that higher total serum cholesterol concentrations may be associated with a modest slower clinical progression of PD, and this preliminary finding needs confirmation from larger prospective studies.
10.1371/journal.pone.0022854
pubmed_862_24697
The nucleophilicity and Lewis basicity of DBU and DBN toward C(sp(2)) centers have been measured: nucleophilicities increase in the series DMAP < DBU < DBN < DABCO while Lewis basicities are DABCO < DMAP < DBU < DBN.
10.1039/b801811a
pubmed_1131_10681
Due to their redox capabilities, thiols have an important role in biological oxidative/reductive processes through the formation of disulfides or their oxidation to into sulfenic, sulfinic, or sulfonic derivatives being also relevant for specific enzyme activities. The mechanisms of these biological pathways often involve metal ion(s). In this case, deciphering metal-assisted transformation of the S-S bond is of primary interest. This report details the reactivity of the disulfide-containing 2,6-bis[(bis(pyridylmethyl)amino)methyl]-4-methylmercaptophenyldisulfide (L(Me(BPA)S-S)) ligand with Cu(II) using different experimental conditions (anaerobic, H2O-only, H2O/O2, or O2-only). Crystallographic snapshots show the formation of tetranuclear disulfide, dinuclear sulfinate, and sulfonate complexes. Mechanistic investigations using Zn(II) as control indicate a non-metal-redox-assisted process in all cases. When present, water acts as nucleophile and attacks at the S-S bond. Under anhydrous conditions, a different pathway involving a direct O2 attack at the disulfide is proposed.
10.1021/acs.inorgchem.6b00819
pubmed_120_16151
Six trypanosomatids isolated from different geographical areas from South America (Peru and Brazil) and different vectors and reservoir hosts (the triatomine Panstrongylus chinai [TP1], Triatoma infestans [TP2], Rhodnius ecuadorensis [TP3], R. prolixus [TB1], Didelphys marsupialis [TB2]), and one from a human asymptomatic patient [TB3], were characterized using lectin agglutination, isoenzyme profile, in vitro culture final metabolite patterns, and compared with a reference strain (Trypanosoma cruzi, Maracay strain [TC]). The different isolates were cultured in vitro in Grace's medium supplemented with 10% inactivated bovine foetal serum. According to our results and the statistical study, the isolate obtained from R. ecuadorensis should be designed as a Trypanosoma rangeli sp., showing all other isolates strong similarities to T. cruzi. Between them, two clusters could be identified, strongly correlating with the geographical origin. Cluster I grouped isolates from Peru and T. cruzi reference strain, and cluster II grouped the three Brazilian isolates.
10.1016/s0014-4894(02)00141-8
pubmed_37_2725
BACKGROUND A study was carried out to describe associations of MC1R variants and melanoma in a US population and to investigate whether genetic risk is modified by pigmentation characteristics and sun exposure measures. METHODS Melanoma patients (n = 960) and controls (n = 396) self-reported phenotypic characteristics and sun exposure via structured questionnaire and underwent a skin examination. Logistic regression was used to estimate associations of high- and low-risk MC1R variants and melanoma, overall and within phenotypic and sun exposure strata. A meta-analysis of results from published studies was undertaken. RESULTS Carriage of 2 low-risk or any high-risk MC1R variants was associated with increased risk of melanoma (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.0-2.8; and OR, 2.2; 95% CI, 1.5-3.0, respectively). However, risk was stronger in or limited to individuals with protective phenotypes and limited sun exposure, such as those who tanned well after repeated sun exposure (OR, 2.4; 95% CI, 1.6-3.6), had dark hair (OR, 2.4; 95% CI, 1.5-3.6), or had dark eyes (OR, 3.2; 95% CI, 1.8-5.9). We noted this same pattern of increased melanoma risk among persons who did not freckle, tanned after exposure to first strong summer sun, reported little or average recreational or occupational sun exposure, or reported no sun burning events. Meta-analysis of published literature supported these findings. CONCLUSIONS These data indicate that MC1R genotypes provide information about melanoma risk in those individuals who would not be identified as high risk based on their phenotypes or exposures alone.
10.1002/cncr.24994
pubmed_207_14270
In order to evaluate the diagnostic capabilities of MR Imaging in defining triangular fibrocartilage (TFC) lesions, 49 selected patients--21 with rheumatoid arthritis, 13 with traumatic injury and 15 with wrist fracture--presenting chronic wrist pain were examined with MR Imaging. The wrists of 12 healthy subjects were also studied as a control group. MR examinations were performed by means of a superconductive 1.0 T unit (Magnetom-Siemens); SE and GE T1- and T2-weighted pulse sequences were employed to acquire images of the wrists on the coronal, axial and, if necessary, sagittal planes. The results showed peripheral TFC tears in 10 cases, central TFC lesions in 12 cases and TFC lesions with collateral insertion involvement in 9 cases. In 4 patients focal thickening of TFC without disruption was observed. The correct diagnosis was made in all the 19 surgically verified cases. Our experience confirms the clinical value of MR Imaging in the evaluation of TFC lesions in patients with chronic ulnar pain syndrome.
pubmed_207_14270
pubmed_605_8044
BACKGROUND Physical inactivity is a leading cause of morbidity, disability and premature mortality in the U.S. and worldwide. This study aimed to map the prevalence of physical inactivity across U.S. states over the past three decades, and estimate the over-time adjusted changes in the prevalence of physical inactivity in each state. METHODS Individual-level data (N = 6,701,954) were taken from the 1984-2015 Behavioral Risk Factor Surveillance System (BRFSS), an annually repeated cross-sectional survey of state-representative adult population. Prevalence of self-reported leisure-time physical inactivity was estimated by state and survey year, accounting for the BRFSS sampling design. Logistic regressions were performed to estimate the changes in the prevalence of physical inactivity over the study period for each state, adjusting for individual characteristics including sex, age, race/ethnicity, education, marital status, and employment status. RESULTS The prevalence of leisure-time physical inactivity varied substantially across states and survey years. In general, the adjusted prevalence of physical inactivity gradually declined over the past three decades in a majority of states. However, a substantial proportion of American adults remain physically inactive. Among the 50 states and District of Columbia, 45 had over a fifth of their adult population without any leisure-time physical activity, and 8 had over 30% without physical activity in 2015. Moreover, the adjusted prevalence of physical inactivity in several states (Arizona, North Carolina, North Dakota, Utah, West Virginia, and Wyoming) remained largely unchanged or even increased (Minnesota and Ohio) over the study period. CONCLUSIONS Although the prevalence of physical inactivity declined over the past three decades in a majority of states, the rates remain substantially high and vary considerably across states. Closely monitoring and tracking physical activity level using the state physical activity maps can help guide policy and program development to promote physical activity and reduce the burden of chronic disease.
10.1371/journal.pone.0168175
pubmed_541_19499
Microbial interaction can be ignored in predictive microbiology under most conditions. We show that interactions are only important at high population densities, using published data on inhibition of growth of Listeria monocytogenes in broth. Our analysis using growth models from predictive microbiology indicated that interactions only occur at population densities of approximately 10(8) cfu/ml of the protective cultures. Spoilage is evident at these levels, except for fermented foods. In bacterial colonies, diffusion limitation acts as a constraint to growth. We have shown that these constraints only become important after large outgrowth of colonies (in the order of 5-log growth in Lactobacillus curvatus colonies), which depends on the initial inoculation density. Intra-colony interactions play an important role under these conditions. There is no large outgrowth of colonies when the initial inoculation densities are high and broth culture growth can be used to approximate colony growth.
10.1016/s0168-1605(02)00424-5
pubmed_820_12470
OBJECTIVES This study was designed to compare the efficacy in supragingival plaque removal of normal toothbrushing practices and a particular toothbrushing technique, the modified Bass method. SUBJECTS AND METHODS The research consisted of two identical experiments with two toothbrushing methods: the normal toothbrushing practices and the modified Bass technique. Forty-six secondary, non-dental students (10 males and 36 females) with ages ranging from 18 to 30 years were selected. Dental plaque was assessed according to the Turesky modification of Quigley-Hein Index. Subjects were requested not to brush their teeth 48 h prior to the baseline record of plaque index. Participants were instructed to brush twice daily during 3 min for the duration of the 3-week trial using their usual toothpaste. Plaque index was recorded at 2, 7 and 21 days. RESULTS The modified Bass (Mod-Bass) technique was significantly (P < 0.05) more effective in removing supragingival plaque than normal toothbrushing practices both in all, buccal and lingual sites. After 21 days, the normal practices did not significantly decrease mean plaque indices compared to the scores calculated after 7 days (P > 0.05), but did so with the modified Bass technique (P < 0.05). The modified Bass technique was specially efficient at the lingual sites where it was 2.9-fold more effective than normal practices in reducing plaque scores (P < 0.01). CONCLUSION The results show that a particular toothbrushing technique as modified Bass method is significantly superior to normal toothbrushing practices in supragingival plaque removal. The introduction of a specific toothbrushing technique, such as modified Bass technique represents an important improvement in the oral hygiene of the patients.
10.1034/j.1601-5037.2003.00018.x
pubmed_478_3449
Musk ambrette (4-tert-butyl-3-methoxy-2,6-dinitrotoluene) is a nitro musk, a cheap substitute for natural musk and a potential environmental pollutant based on its persistence, accumulation in human organisms. We investigated the acute toxicity of musk ambrette using wild-type AB and transgenic Tg(fli1a:EGFP)y1 zebrafish. Different concentrations were delivered to zebrafish by direct soaking from 6 to 72 h post-fertilization (hpf). The LC50 of musk ambrette was 76.4 µg mL-1. As musk ambrette concentration increased, zebrafish embryos showed developmental delays (50 µg mL-1, 22 hpf), pericardial edema (5 µg mL-1, 48 hpf), circulatory disturbances, curved body axis (1 µg mL-1, 72 hpf) and death (100 µg mL-1, 22 hpf). Target organ toxicity was evaluated by a zebrafish angiogenesis model. Musk ambrette induced cardiovascular morphological changes, vessel permeability variation, angiogenic changes and cardiotoxicity (10 µg mL-1, 48 hpf). The disappearance of caudal vein plexus confirmed the vascular development toxicity. Musk ambrette negatively affects early life-stage survival and demonstrates various toxicities in zebrafish.
10.1007/s00128-018-2363-z
pubmed_370_10006
Transport, unidirectional flux, of a monosaccharide, a nucleoside and three amino acids, all of which enter cells by independent, discrete carriers, was compared at three stages of erythroid maturation, the normal (anucleate) mouse erythrocyte, and in differentiated and undifferentiated Friend erythroleukemia cells. We found specific transport alterations during this developmental program. Transport of 3-O-methylglucose increased with each successive developmental stage. Aminoisobutyrate transport was maintained during Friend cell differentiation, but fell slightly in erythrocytes. Leucine, lysine and uridine transport began to fall two days after dimethylsulfoxide exposure, and diminished further in red cells. These studies of transport are not directly comparable to uptake studies reported by others. Median cell volume and thus surface area decreased more during differentiation than amino acid transport declined, so flux, transport past a unit area of membrane, actually increased. Monosaccharide flux also increased. Only uridine transport fell in parallel to surface area. Perhaps sites for nutrient transport required for energy production are preferentially maintained.
10.1007/BF01870764
pubmed_0_15918
The intracellular bacterial pathogen Listeria monocytogenes secretes a broad-range phospholipase C enzyme called PC-PLC (phosphatidylcholine phospholipase C) whose compartmentalization and enzymatic activity is regulated by a 24-amino-acid propeptide (Cys28-Ser51). During intracytosolic multiplication, bacteria accumulate the proform of PC-PLC at their membrane-cell-wall interface, whereas during cell-to-cell spread vacuolar acidification leads to maturation and rapid translocation of PC-PLC across the cell wall in a manner that is dependent on Mpl, the metalloprotease of Listeria. In the present study, we generated a series of propeptide mutants to determine the minimal requirement to prevent PC-PLC enzymatic activity and to identify residues regulating compartmentalization and maturation. We found that a single residue at position P1 (Ser51) of the cleavage site is sufficient to prevent enzymatic activity, which is consistent with P1' (Trp52) being located within the active-site pocket. We observed that mutants with deletions at the N-terminus, but not the C-terminus, of the propeptide are translocated across the cell wall more effectively than wild-type PC-PLC at a physiological pH, and that individual amino acid residues within the N-terminus influence Mpl-mediated maturation of PC-PLC at acidic pH. However, deletion of more than 75% of the propeptide was required to completely prevent Mpl-mediated maturation of PC-PLC. These results indicate that the N-terminus of the propeptide regulates PC-PLC compartmentalization and that specific residues within the N-terminus influence the ability of Mpl to mediate PC-PLC maturation, although a six-residue propeptide is sufficient for Mpl to mediate PC-PLC maturation.
10.1042/BJ20100557
pubmed_214_2905
INTRODUCTION Time series models play an important role in monitoring and understanding the serial dynamics of road crash exposures, risks, outcomes, and safety performance indicators. The time-series methods applied in previous studies on crash time series analysis assume that the serial dependency decays rapidly or even exponentially. However, this assumption is violated in most cases because of the existence of long-memory properties in the crash time series data. Ignoring the long-memory dependency could result in biased understanding of the dynamics of road traffic crashes. METHOD To fill this research gap, this study proposes an autoregressive fractionally integrated moving average model with generalized autoregressive conditional heteroscedasticity (ARFIMA-GARCH) to capture and accommodate the long-memory decencies in the road fatality rate time series. To further investigate how the factors influencing the fatality risks play a role in the long-memory dependence, the effects of exogenous variables are examined in this study. The analysis is conducted based on the road crash fatality data in Florida, USA over 44 years. Results' Conclusions: The case analysis confirmed the existence of long-memory property in the crash fatality time series data by both the joint tests of Augmented Dickey-Fuller and the Phillips-Perron, and the integer order of differencing (≤0.5) in the proposed models. The model results reveal that gasoline price and alcohol consumption per capita is positively associated with road fatality risks, whereas unemployment rate and rural/urban road mileage are negatively related to the road fatality risks. PRACTICAL APPLICATIONS The significant influential factors are also found to account for the long-memory serial correlations between road traffic fatalities to some extent.
10.1016/j.jsr.2022.02.013
pubmed_9_20841
By quantitation of elutable immunoglobulin G in a recently described ELISA, the number of HLA class I and II molecules on B-cell lines was determined using monomorphic monoclonal antibodies. An average number of 183,000 binding sites per cell for HLA class I-, 99,000 for HLA-DR-, 63,000 for DQ- and 42,000 for DP-specific monoclonal antibodies were determined. The small amount of HLA class II molecules can in part explain the difficulties observed in HLA class II typing or in detection of class II antibodies using the lymphocytotoxicity text.
10.1111/j.1744-313x.1993.tb00109.x
pubmed_722_6861
Although the deferred and non-prosecution agreements entered into by five of the leading orthopaedic implant companies have caused our profession to re-examine the surgeon-industry partnerships that have helped advance the field, the legal and ethical considerations in that relationship have not changed. Moving forward, the surgeon must recognize that a truly valuable exchange must be demonstrated and delivered in that relationship for compensation to be warranted. This paper summarizes the value proposition in the orthopaedic surgeon-industry partnership.
pubmed_722_6861
pubmed_290_10948
BACKGROUND AND OBJECTIVE This study aimed to establish reference equations for spirometry in healthy Taiwanese children and assess the applicability of the Global Lung Function Initiative (GLI)-2012 equations to Taiwanese children. METHODS Spirometric data collected from 757 healthy Taiwanese children aged 5 to 18 years in a population-based cohort study. Prediction equations derived using linear regression and the generalized additive models for location, scale and shape (GAMLSS) method, respectively. RESULTS The GLI-2012 South East Asian equations did not provide a close fit with mean ± standard error z-scores of -0.679 ± 0.030 (FVC), -0.186 ± 0.044 (FEV1), -0.875 ± 0.049 (FEV1/FVC ratio) and -2.189 ± 0.063 (FEF25-75) for girls; and 0.238 ± 0.059, -0.061 ± 0.053, -0.513 ± 0.059 and -1.896 ± 0.077 for boys. The proposed GAMLSS models took age, height, and weight into account. GAMLSS models for boys and girls captured the characteristics of spirometric data in the study population closely in contrast to the linear regression models and the GLI-2012 equations. CONCLUSION This study provides up-to-date reference values for spirometry using GAMLSS modeling in healthy Taiwanese children aged 5 to 18 years. Our study provides evidence that the GLI-2012 reference equations are not properly matched to spirometric data in a contemporary Taiwanese child population, indicating the urgent need for an update of GLI reference values by inclusion of more data of non-Caucasian decent.
10.1016/j.waojou.2019.100074
pubmed_1121_20143
BACKGROUND Tuberculum sellae meningiomas have an incidence from 5 to 10% of all intracranial meningiomas[2] and tend to be surgically difficult and challenging tumors given their proximity to important structures such as the internal carotid artery (ICA), anterior cerebral artery (ACA), and optic nerves.[3] Typically, their growth is posteriorly and superiorly oriented, thereby displacing the optic nerves and causing visual dysfunction, which is the primary indication for surgical treatment.[1] The main goals of the treatment are the preservation or restoration of visual abilities and a complete tumor resection.[1] Conventionally, surgical approaches to tuberculum meningiomas involve largely invasive extended bifrontal, interhemispheric, orbitozygomatic, pterional, and subfrontal eyebrow approaches. The supraorbital craniotomy, however, is a minimally invasive transcranial approach that offers a similar surgical corridor to conventional transcranial approaches, using a limited craniotomy and minimal brain retraction that can be used for tumoral and vascular pathologies,[4,5] offering added cosmetic outcomes.[1] We present the case of a patient undergoing a supraorbital transciliary craniotomy with a tuberculum sellae meningioma causing bitemporal hemianopsia. CASE DESCRIPTION A 70-year-old female with chronic headaches and progressive vision loss and visual field deficit for about 1 year. On ophthalmological evaluation, she was able to fixate and follow objects with each eye, light perception was only present in the right eye, and the vision in the left eye was 0.2 decimal units. Her visual fields demonstrated severe campimetric deficits. Her extraocular movements were intact and bilateral pupils were equal, round, and reactive to light. MRI of the brain demonstrated tuberculum sellae meningioma with bilateral optic canal invasion, displacing the chiasm, and extending ≥180° around the medial ICA wall and anterior ACA wall. The patient underwent supraorbital transciliary keyhole approach for total resection of the tumor. Postoperatively, visual acuity and visual field were significantly improved. CONCLUSION Performing a supraorbital transciliary keyhole craniotomy for tuberculum sellae meningiomas requires an adequate and meticulous preoperative planning to determine the optimal surgical corridor to the lesion. The use of supraorbital craniotomy is safe with good cosmetic results and potentially lower morbidity allowing for adequate exposure, resection, and release of neurovascular structures.
10.25259/SNI_731_2020
pubmed_675_21336
Silk fibroin is a protein with a unique combination of properties and is widely studied for biomedical applications. The extraction of fibroin (degumming) from the silk filament impacts the properties of the outcoming material. The degumming can be conducted with different procedures. Among them, the most used and studied procedure in the research field is the alkali degumming with sodium carbonate (Na2CO3). In this study, by the use of a statistical method, namely, design of experiment (DOE), we characterized the Na2CO3 degumming, taking into consideration the main process factors involved and changing them within a selected range of values. We considered the process temperature and time, the salt concentration, and the number of baths used, testing the impact of these variables on the fibroin properties by building empirical models. These models not only took into consideration the direct effect of the process factors but also their combined effect, which are not conventionally detectable with other methods. The weight loss and the amount of sericin removed in the process were determined and used as a measure of the effectiveness of the process. The secondary structure, the molecular weight, the diameter of fibers, and their morphology and mechanical properties were studied with the intent to correlate the macroscopical properties with the structural changes. We report, for the first time, the possibility to effectively remove all sericin from the silk fibroin using Na2CO3, using a process that requires less salt, water, and energy, in comparison with the standard alkali protocol, making this technique overall more environmentally sustainable; in addition, we have demonstrated the possibility to tune the material properties by varying the degumming conditions and even to optimize them with empirical statistically based equations that allow one to directly set the optimal process parameters. The major effect on the macroscopical properties (such as the ultimate strength and Young's modulus) has been proved to be correlated with the removal of sericin instead of the microstructural variations. Finally, a ready-to-use table with a set of optimized degumming procedures to maximize or minimize the studied properties was provided.
10.1021/acsbiomaterials.0c01657
pubmed_666_18902
BACKGROUND Hump recurrence is a commonly encountered problem following dorsal preservation (DP) rhinoplasty when surgeons are learning the procedure. OBJECTIVES The aim of this paper was to compare the different methods for the prevention and treatment of dorsal problems following DP surgery. METHODS One hundred and fifty primary rhinoplasty patients were included in our study. Their noses were classified in terms of both hump shape (V- or S-shaped) and height. All patients had a DP rhinoplasty by either a push-down (PD) or a let-down (LD) technique. The PD method was used for humps <4 mm and the LD for humps >4 mm. Follow-up evaluations were made with physical examination and photographs at 1 week, 3 months, and 12 months. RESULTS Mean follow-up was 12.68 [1.78] months. Seventy-eight humps were V-shaped and 72 were S-shaped. PD was used for 67 cases, LD for 83 cases. Eight patients (5.3%, 8/150) had a visible dorsal hump problem after DP surgery. Based on their preoperative hump shape, 3 cases were V-shaped and 5 were S-shaped. All recurrent cases had a preoperative hump deformity >4 mm. The revision procedures were as follows: 4 patients had a PD procedure, 3 had a LD procedure, and 1 patient was treated by classic open resection rhinoplasty. CONCLUSIONS There is a correlation between preoperative hump height and eventual hump recurrence. The complication rate can be decreased with additional technical maneuvers and proper patient selection. LEVEL OF EVIDENCE: 4
10.1093/asj/sjaa145
pubmed_697_13041
BACKGROUND Accurate clinical documentation (CD) is necessary for many aspects of modern health care, including excellent communication, quality metrics reporting, and legal documentation. New requirements have mandated adoption of ICD-10-CM coding systems, adding another layer of complexity to CD. A clinical documentation improvement (CDI) and ICD-10 training program was created for health care providers in our academic surgery department. We aimed to assess the impact of our CDI curriculum by comparing quality metrics, coding, and reimbursement before and after implementation of our CDI program. STUDY DESIGN A CDI/ICD-10 training curriculum was instituted in September 2014 for all members of our university surgery department. The curriculum consisted of didactic lectures, 1-on-1 provider training, case reviews, e-learning modules, and CD queries from nurse CDI staff and hospital coders. Outcomes parameters included monthly documentation completion rates, severity of illness (SOI), risk of mortality (ROM), case-mix index (CMI), all-payer refined diagnosis-related groups (APR-DRG), and Surgical Care Improvement Program (SCIP) metrics. Financial gain from responses to CDI queries was determined retrospectively. RESULTS Surgery department delinquent documentation decreased by 85% after CDI implementation. Compliance with SCIP measures improved from 85% to 97%. Significant increases in surgical SOI, ROM, CMI, and APR-DRG (all p < 0.01) were found after CDI/ICD-10 training implementation. Provider responses to CDI queries resulted in an estimated $4,672,786 increase in charges. CONCLUSIONS Clinical documentation improvement/ICD-10 training in an academic surgery department is an effective method to improve documentation rates, increase the hospital estimated reimbursement based on more accurate CD, and provide better compliance with surgical quality measures.
10.1016/j.jamcollsurg.2016.11.010
pubmed_1123_4346
Systemic manifestations of allergic contact dermatitis due to consumption of foods containing balsam of Peru (Myroxylon pereirae)-associated chemicals have recently been reported in children. We present seven children with widespread, recalcitrant dermatitis who experienced 60-80% clearance after initiating a diet low in balsam of Peru, specifically the tomato product ketchup. Furthermore, because we have observed a high prevalence of ketchup in our pediatric patients' diets, we recommend consideration of moderate consumption of this product in patients with recalcitrant widespread dermatitis.
10.1111/j.1525-1470.2011.01702.x
pubmed_947_16678
The metabolic cost of human running is not well explained, in part because the amount of work performed actively by muscles is largely unknown. Series elastic tissues such as tendon can save energy by performing work passively, but there are few direct measurements of the active versus passive contributions to work in running. There are, however, indirect biomechanical measures that can help estimate the relative contributions to overall metabolic cost. We developed a simple cost estimate for muscle work in humans running (N = 8) at moderate speeds (2.2-4.6 m/s) based on measured joint mechanics and passive dissipation from soft tissue deformations. We found that even if 50% of the work observed at the lower extremity joints is performed passively, active muscle work still accounts for 76% of the net energetic cost. Up to 24% of this cost compensates for the energy lost in soft tissue deformations. The estimated cost of active work may be adjusted based on assumptions of multi-articular energy transfer, elasticity, and muscle efficiency, but even conservative assumptions yield active work costs of at least 60%. Passive elasticity can reduce the active work of running, but muscle work still explains most of the overall energetic cost.
10.1038/s41598-021-04215-6
pubmed_234_12961
Convolutions of independent random variables are usually compared. In this paper, after a synthetic comparison with respect to hazard rate ordering between sums of independent exponential random variables, we focus on the special case where one sum is identically distributed. So, for a given sum of n independent exponential random variables, we deduce the "best" Erlang-n bounds, with respect to each of the usual orderings: mean ordering, stochastic ordering, hazard rate ordering and likelihood ratio ordering.
10.1023/a:1009605613222
pubmed_50_16701
Sandwich compounds represent the only class of organometallics revealing vibronic structures of Rydberg transitions in their gas-phase absorption and ionization spectra. This provides rare possibilities of verifying computational results for Rydberg-state metal complexes by comparison with experimental spectroscopic data. In this work, the lowest Ryberg p state of bis(η6-benzene)chromium (1) corresponding to the 3dz→ R4px,y transition has been modeled for the first time by TD DFT. The calculations were found to be able not only to estimate the energy of the Rydberg excitation in the 1 molecule but also to simulate its vibronic structure on the basis of the Rydberg-state optimized geometries and vibrational frequencies. The structural transformations caused by the Jahn-Teller effect in the excited 1 molecule appear to differ strongly from those in the degenerate-state benzene ion, cobaltocene or other metal-benzene complexes. The in-plane CH bending mode provides the main contribution to the JT distortion of the 1 excited-state D6h structure resulting in splitting of the R4px,y state into the R4px and R4py components belonging to the D2h point group. The calculations predict, however, a fluxional 1 behavior described by the D6h symmetry. Nevertheless, the JT effect leads to additional allowed vibronic components of the 3dz→ R4px,y transition which is clearly revealed by the TD DFT simulation. The computational results correlate surprisingly well with the known experimental spectroscopic data and provide new insights into vibronic interactions in the Rydberg-state sandwich molecules.
10.1039/c8cp04845b
pubmed_217_4038
BACKGROUND Gastric cancer (GC) is one of the most common types of cancer in the world. A change in the metabolism of lipids in tumor cells could lead to the pathogenesis of cancer. In this study, we investigated fatty acid and fatty acid amide metabolic perturbations associated with GC morbidity. METHODS Gas chromatography/mass spectrometry (GC/MS) was utilized to analyze fatty acids (FAs) and fatty acid amides (FAAs) of GC tissues and matched normal mucosae from 30 GC patients. Acquired lipid data was analyzed using non parametric Wilcoxon rank sum test to find the differential biomarkers for GC and diagnostic models for GC were established by using orthogonal partial least squares discriminant analysis (OPLS-DA). RESULTS A total of 13 FAs and 4 FAAs were detected using GC/MS and 5 differential FAs as well as oleamide were identified with significant difference (P<0.05). The OPLS-DA model generated from lipid profile showed adequate discrimination of GC tissues from normal mucosae while the OPLS-DA model failed to separate GC specimens of different TNM stages. A total of 8 variables were obtained for their most contribution in the discriminating model (Variable importance in the projection (VIP) value>1.0), five of which were detected with significant difference (P<0.05). CONCLUSIONS FA and FAA metabolic profiles have great potential in detecting GC and helping understand perturbations of lipid metabolism associated with GC morbidity.
pubmed_217_4038
pubmed_480_4581
INTRODUCTION Despite advances in treatment, infective endocarditis (IE) still ranks amongst the most lethal infectious diseases. We sought to determine prognostic factors in general hospitals in the Netherlands as research in this setting is scarce. RESULTS Between 2004 and 2011, we identified 216 cases of IE, 30.1 % of which were prosthetic valve IE. This leads to an annual incidence of IE of 5.7 new cases per 100,000 persons per year. Women were less likely to undergo surgical intervention (OR = 1.96, 95 % CI 1.06-3.61, p = 0.031). Also, ageing was an independent prognostic factor for not receiving surgery in a multivariate analysis (annual OR = 1.04, 95 % CI 1.02-1.06, p < 0.001). Female sex was a prognostic factor for mortality (OR = 2.35, 95 % CI 1.29-4.28, p = 0.005). Age was also an independent prognostic factor for mortality (OR = 1.05, 95% CI 1.03-1.08, p < 0.001). Conservative treatment was a prognostic factor for mortality (OR = 3.39, 95 % CI 1.80-6.38, p < 0.001) whereas surgical intervention was an independent prognostic factor for adverse events (OR = 3.03, 95% CI 1.64-5.55, p < 0.001). Staphylococcus aureus was an independent prognostic factor for adverse events (OR = 2.05, 95 % CI 1.10-3.84, p = 0.024) but not for mortality. CONCLUSION This study shows that endocarditis in general hospitals has a high rate of morbidity and mortality. Even when treated, it ranks as one of the most lethal infectious diseases in the Netherlands, especially in women and the elderly.
10.1007/s12471-016-0846-2
pubmed_437_21681
Ternary mixtures being composed of surfactant, long-chain alcohol, and water sometimes form a highly viscous lamellar gel with a hexagonal packing arrangement of their crystalline hydrocarbon chains. This molecular assembly is called "α-crystalline phase" or "α-gel". In this study, we have characterized α-gels formed by the ternary mixtures of amino acid-based gemini surfactants, 1-hexadecanol (C16OH), and water. The surfactants used in this study were synthesized by reacting dodecanoylglutamic acid anhydride with alkyl diamines and abbreviated as 12-GsG-12 (s: the spacer chain length of 2, 5, and 8 methylene units). An amino acid-based monomeric surfactant, dodecanoylglutamic acid (12-Glu), was also used for comparison. At a fixed water concentration the melting point of the α-gel increased with increasing C16OH concentration, and then attained a saturation level at the critical mole ratio of 12-GsG-12/C16OH = 1/2 under the normalization by the number of hydrocarbon chains of the surfactants. This indicates that, to obtain the saturated α-gel, a lesser amount of C16OH is required for the gemini surfactants than for the monomeric one (the critical mole ratio of 12-Glu/C16OH = 1/3). Small- and wide-angle X-ray scattering measurements demonstrated an increase in the long-range d-spacing of the saturated α-gels in the order 12-Glu <12-G8G-12 < 12-G5G-12 < 12-G2G-12. In the three gemini surfactant systems, the decreased spacer chain length resulted in the increased maximum viscosity and elastic modulus of the saturated α-gels at a given water concentration. This is caused by the decreased amount of excess water being present outside the α-gel structure (or the increased amount of water incorporated between the surfactant-alcohol bilayers). To the best of our knowledge, this is the first report focusing on the formation of α-gel in gemini surfactant systems.
10.1021/la501186h
pubmed_611_18145
The present study was designed to determine the effects of melatonin on coronary vasomotor tone. Porcine coronary arteries were suspended in organ chambers for isometric tension recording. Melatonin (10(-10)-10(-5) M) itself caused neither contraction nor relaxation of the tissues. Serotonin (10(-9)-10(-5) M) caused concentration-dependent contractions of coronary arteries, and in the presence of melatonin (10(-7) M) the maximal response to serotonin was increased in rings with but not without endothelium. In contrast, melatonin had no effect on contractions produced by the thromboxane A(2) analog U-46619 (10(-10)-10(-7) M). The melatonin-receptor antagonist S-20928 (10(-6) M) abolished the potentiating effect of melatonin on serotonin-induced contractions in endothelium-intact coronary arteries, as did treatment with 1H-[1, 2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10(-5) M), methylene blue (10(-5) M), or N(G)-nitro-L-arginine (3 x 10(-5) M). In tissues contracted with U-46619, serotonin caused endothelium-dependent relaxations that were inhibited by melatonin (10(-7) M). Melatonin also inhibited coronary artery relaxation induced by sodium nitroprusside (10(-9)-10(-5) M) but not by isoproterenol (10(-9)-10(-5) M). These results support the hypothesis that melatonin, by inhibiting the action of nitric oxide on coronary vascular smooth muscle, selectively potentiates the vasoconstrictor response to serotonin in coronary arteries with endothelium.
10.1152/ajpheart.2001.280.1.H76
pubmed_1061_21759
Diosgenin (Di), a steroidal sapogenin derived from plants, has been shown to exert anticancer effects in preclinical studies. Using Di as a starting material, various Di derivatives were designed and synthesized, aiming to discover new steroid-based antitumor agents. In this work, we synthesized several Di derivatives and screened FZU-0021-194-P2 (P2), which showed more potent cytotoxic activities against human non-small-cell lung cancer A549 and PC9 cells. Considering that Di has a unique sterol structure similarly to cholesterol, P2 phytosomes (P2Ps) were prepared to further improve the water solubility of P2. The P2Ps exhibited a particle size of 53.6 ± 0.3 nm with oval shape and a zeta potential of -4.0 ± 0.7 mV. P2Ps could inhibit the proliferation of lung cancer cells more efficiently than Di phytosomes after 72 h of incubation time by inducing cell cycle arrest and apoptosis. The results indicated that P2Ps could be a promising anticancer formulation for non-small-cell lung cancer.
10.3762/bjnano.10.189
pubmed_249_10658
Equilibrium unfolding experiments on several mutant forms of horse heart cytochrome c were performed. By means of absorbance spectroscopy, the accumulation of an equilibrium intermediate was revealed upon unfolding of Y97V mutant protein, and its structural properties were characterized. The data obtained allow one to conclude that the equilibrium intermediate corresponds to the earliest kinetic intermediate Ic in cytochrome c folding reaction. A comparative analysis of spectral properties of unfolded states of cytochrome c induced by urea or guanidine hydrochloride is presented.
pubmed_249_10658
pubmed_763_5111
A novel electrochemical sensor has been fabricated using Co doped CeO2 nanoparticles for selective and simultaneous determination of xanthine (XA), hypoxanthine (HXA) and uric acid (UA) in a phosphate buffer solution (PBS, pH5.0) for the first time. The Co-CeO2 NPs have been prepared by microwave irradiation method and characterized by Powder XRD, Raman spectroscopy, HRTEM and VSM measurements. The electrochemical behaviours of XA, HXA and UA at the Co-CeO2 NPs modified glassy carbon electrode (GCE) were studied by cyclic voltammetry and square wave voltammetry methods. The modified electrode exhibited remarkably well-separated anodic peaks corresponding to the oxidation of XA, HXA and UA over the concentration range of 0.1-1000, 1-600 and 1-2200μM with detection limits of 0.096, 0.36, and 0.12μM (S/N=3), respectively. For simultaneous detection by synchronous change of the concentrations of XA, HXA and UA, the linear responses were in the range of 1-400μM each with the detection limits of 0.47, 0.26, and 0.43μM (S/N=3), respectively. The fabricated sensor was further applied to the detection of XA, HXA and UA in human urine samples with good selectivity and high reproducibility.
pubmed_763_5111
pubmed_934_9492
BACKGROUND At least three genetic factors including beta-thalassemia mutations, alpha-thalassemia, and XmnI-Ggamma polymorphism were shown to modify clinical symptoms in beta-thalassemia disease. OBJECTIVE To determine associations of beta-thalassemia mutations, SEA-alpha thalassemia 1, and XmnI-Ggamma polymorphism, and clinical severity of beta-thalassemia in northern Thailand. MATERIAL AND METHOD Thirty-two beta-thalassemia major and 28 beta-thalassemia intermedia attending the Thalassemia Clinic at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand were recruited The beta-globin gene mutations and SEA-alpha thalassemia 1 were determined by MS-PCR and Gap-PCR, respectively. The XmnI-Ggamma polymorphism was identified by RFLP analysis. Odds ratio was calculated to evaluate the associations of these three genetic factors and clinical symptoms. RESULTS Eight beta-globin gene mutations (both beta0 and beta+) were found Twenty-nine point one percent of the patients had at least one XmnI-Ggamma site (XmnI-Ggamma: +) and 4.1% of the patients were heterozygote for the SEA-alpha thalassemia 1. The beta-globin gene mutations showed maximal impact and the XmnI-Ggamma polymorphism had minimal influence on clinical severity in this cohort. The SEA-alpha thalassemia 1 had the least effect on the clinical severity due to its low prevalence in these patients. CONCLUSION Although these three genetic factors play roles in modifying clinical symptoms of beta-thalassemia, the beta-thalassemia mutations should be considered first, followed respectively by the XmnI-Ggamma polymorphism and the SEA-alpha thalassemia 1, in management and prenatal diagnosis of beta-thalassemia in northern Thailand.
pubmed_934_9492
pubmed_27_4123
We have previously shown that adenovirus E1A proteins can block interferon-alpha (IFN-alpha)-signalling. In the current study, we examined if the same is true for IFN-gamma signaling. Cotransfection experiments showed that both 289R and 243R forms of E1A could block the expression of an IFN-gamma-inducible reporter gene. Similarly, in an E1A-expressing HeLa cell line IFN-gamma failed to induce the synthesis of IRF-1 mRNA. This failure was due to a block in activation of the crucial trans-acting factor, GAF, which in turn was due to the lack of IFN-gamma-activated tyrosine phosphorylation of the STAT1 alpha protein in E1A-expressing cells. The above defect could be attributed to a reduced level of STAT1 alpha protein. The level of p48 protein, which is required for IFN-alpha signaling, was also lowered. However, the level of lak-1 protein, one of the tyrosine kinases necessary for both IFN-alpha and IFN-gamma signalling, was comparable in the E1A-expressing and the control cells. These results indicate that the observed inhibition of IFN signalling in E1A-expressing cells is a consequence of a lower abundance of the necessary trnas-acting factors.
10.1006/viro.1996.0503
pubmed_1037_24883
Background Integrated PET/MRI is a promising modality for breast assessment. The most frequently used tracer, fluorine 18 (18F) fluorodeoxyglucose (FDG), is applied for whole-body staging in advanced breast cancer but has limited accuracy in evaluating primary breast lesions. The fibroblast-activation protein (FAP) is abundantly expressed in invasive breast cancer. FAP-directed PET tracers have recently become available, but results in primary breast tumors remain lacking. Purpose To evaluate the use of FAP inhibitor (FAPI) breast PET/MRI in assessing breast lesions and of FAPI whole-body scanning for lymph node (LN) and distant staging using the ligand gallium 68 (68Ga)-FAPI-46. Materials and Methods In women with histologically confirmed invasive breast cancer, all primary 68Ga-FAPI-46 breast and whole-body PET/MRI and PET/CT examinations conducted at the authors' center between October 2019 and December 2020 were retrospectively analyzed. MRI lesion characteristics and standardized uptake values (SUVs) were quantified with dedicated software. Mann-Whitney U tests were used to compare tumor SUVs across different tumor types. The Pearson correlation coefficient was calculated between SUV and measures of MRI morphologic characteristics. Results Nineteen women (mean age, 49 years ± 9 [standard deviation]) were evaluated-18 to complement initial staging and one for restaging after therapy for distant metastases. Strong tracer accumulation was observed in all 18 untreated primary breast malignancies (mean maximum SUV [SUVmax] = 13.9 [range, 7.9-29.9]; median lesion diameter = 26 mm [range, 9-155 mm]), resulting in clear tumor delineation across different gradings, receptors, and histologic types. All preoperatively verified LN metastases in 13 women showed strong tracer accumulation (mean SUVmax= 12.2 [range, 3.3-22.4]; mean diameter = 21 mm [range, 14-35 mm]). Tracer uptake established or supported extra-axillary LN involvement in seven women and affected therapy decisions in three women. Conclusion This retrospective analysis indicates use of 68Ga fibroblast-activation protein inhibitor tracers for breast cancer diagnosis and staging. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Mankoff and Sellmyer in this issue.
10.1148/radiol.2021204677
pubmed_76_20106
The activity of clarithromycin alone and in combination with other antimycobacterial agents was evaluated in the beige (C57BL/6J bgj/bgj) mouse model of disseminated Mycobacterium avium complex (MAC) infection. A dose-response experiment was performed with clarithromycin at 50, 100, 200, or 300 mg/kg of body weight administered daily by gavage to mice infected with approximately 10(7) viable MAC. A dose-related reduction in spleen and liver cell counts was noted with treatment at 50, 100, and 200 mg/kg. The difference in cell counts between treatment at 200 and 300 mg/kg was not significant. Clarithromycin at 200 mg/kg of body weight was found to have activity against three additional MAC isolates (MICs for the isolates ranged from 1 to 4 micrograms/ml by broth dilution). Clarithromycin at 200 mg/kg in combination with amikacin, ethambutol, temafloxacin, or rifampin did not result in increased activity beyond that seen with clarithromycin alone. Clarithromycin in combination with clofazimine or rifabutin resulted in an increase in activity beyond that seen with clarithromycin alone. The combination of clarithromycin with clofazimine or rifabutin should be considered for evaluation in the treatment of human MAC infections.
10.1128/AAC.36.11.2413
pubmed_605_16063
Cancer arises from a series of genetic and epigenetic changes, which result in abnormal expression or mutational activation of oncogenes, as well as suppression/inactivation of tumor suppressor genes. Aberrant expression of coding genes or long non-coding RNAs (lncRNAs) with oncogenic properties can be caused by translocations, gene amplifications, point mutations or other less characterized mechanisms. One such mechanism is the inappropriate usage of normally dormant, tissue-restricted or cryptic enhancers or promoters that serve to drive oncogenic gene expression. Dispersed across the human genome, endogenous retroviruses (ERVs) provide an enormous reservoir of autonomous gene regulatory modules, some of which have been co-opted by the host during evolution to play important roles in normal regulation of genes and gene networks. This review focuses on the "dark side" of such ERV regulatory capacity. Specifically, we discuss a growing number of examples of normally dormant or epigenetically repressed ERVs that have been harnessed to drive oncogenes in human cancer, a process we term onco-exaptation, and we propose potential mechanisms that may underlie this phenomenon.
10.1186/s13100-016-0080-x
pubmed_871_2058
Linkage tests to localize oligogenes have been extended during the past year. Using simulated data and multiplex selection we find that several tests on affected sib pairs have comparable power and type I error. Three variants of SIBPAL2 are favoured when substantial numbers of normal sibs are included, but performance relative to the BETA benchmark degrades rapidly as normal sibs are depleted by selective sampling or typing. Neglect of this fact may explain recent failure of retrospective collaboration to confirm asthma candidates in the 5q cytokine region that are supported by other studies. A fully quantitative trait favours variance components under complete ascertainment and two options in SIBPAL2 under multiplex selection, with substantial gain in power from covariance analysis if the covariate is independent of the candidate locus. A dichotomy and liability threshold give virtually identical results in the SOLAR variance components program. Comparison with single-marker parametric analysis suggests that extension to multiple markers would be competitive with nonparametric methods in power, and superior in depth of genetic analysis. The simulated examples illustrate common problems encountered with linkage scans for oligogenes. They show that nonparametric methods provide no panacea for analytical problems posed by different phenotypes and methods of ascertainment.
10.1017/S0003480001008971
pubmed_1075_10975
The poor prognosis for patients with glioblastoma (GB) heightens the importance of maintaining function throughout treatment. Hyperglycemia has been linked to poor neurological outcomes following stroke, traumatic brain and spinal cord injury. We hypothesized this may also be true following the resection of GB. We assessed associations with post-operative function with the goal of identifying modifiable factors in the peri-operative period with a particular focus on blood glucose levels. Independent associations with worse post-operative function included: patient age, pre-operative motor deficit, deep tumor location, post-operative motor deficit, and elevated mean peri-operative glucose. Interestingly, controlling for associated factors including dexamethasone dosing, patients with elevated peri-operative glucose levels were nearly twice as likely to have new post-operative neurological deficits. These results suggest, together with the broad literature supporting a role for hyperglycemia in neurological injury, that this may represent a modifiable factor in the peri-operative care of these patients.
10.1016/j.jocn.2011.09.031
pubmed_1058_1930
We describe the first experiments to relate the cerebral kinetics of isoflurane (determined by fluorine magnetic resonance spectroscopy) to cerebral function. Using a surface receive coil we found two-compartment kinetics within the head with equilibrium half-times of 3.5 min and approximately 1 h with respect to expired isoflurane concentrations. Using critical fusion flicker frequency as an objective measure of the cerebral effect of isoflurane, we found evidence to identify the fast component as the brain. Responsiveness to command was lost at a brain partial pressure of 0.3% isoflurane. We conclude that the measured cerebral kinetics of isoflurane exactly matched the predictions of the classical perfusion-limited model.
10.1093/bja/79.5.586
pubmed_590_22278
The use of the 70° arthroscope in knee surgery is not a new concept, and it is frequently used in posterior cruciate ligament reconstruction. There are previous reports of its use in anterior cruciate ligament surgery, but it has not achieved routine use. With the move toward anatomic anterior cruciate ligament reconstruction, it is recognized that accurate tunnel placement is vital for a good clinical outcome. Visualization of the femoral and tibial footprints can be variable with the use of only an anterolateral viewing portal, and it may be necessary to create accessory anteromedial portals, which can cause problems with instrument crowding. Overall, the 70° arthroscope provides an excellent view of the femoral and tibial footprints and a view of the full length of the femoral and tibial tunnels through a single anterolateral viewing portal.
10.1016/j.eats.2013.08.001
pubmed_465_13895
Critical fusion frequency (CFF) of toad rods was examined at various intensities using intracellular recordings. Data were compared to CFF measurements (as a function of intensity) obtained with the electroretinogram (ERG) and with a horizontal cell. In all instances the rod (and rod mediated) responses produced a curve which increased monotonically to a high frequency asymptote at about 6 Hz. The curves obtained with the ERG and the horizontal cell were double branched. The upper branch exhibited a Purkinje shift and thus must have been produced by cones. Even when using a red background to suppress cone sensitivity, there was no sign of a second rod mediated branch in the CFF curves from this retina.
10.1016/0042-6989(83)90051-2
pubmed_861_2152
Purpose: United States Medical Licensing Examination (USMLE) Step 1 and Step 2 Clinical Knowledge (CK) scores are frequently used to evaluate applicants to residency programs. Recent literature questions the value of USMLE scores for evaluation of residency applicants, in part due to a lack of evidence supporting a relationship with clinical performance. This study explored the relationship between USMLE scores and medical students' clinical performance, as measured by the count of honors grades received in core clinical clerkships. Methods: USMLE Step 1 and Step 2 CK scores and number of honors grades per student in seven core clinical clerkships were obtained from 1,511 medical students who graduated in 2013-2017 from two medical schools. The relationships between variables were analyzed using correlation coefficients, independent-samples t-tests, and hierarchical multiple regression. Results: Count of honors grades correlated with both Step 1 (R=0.480, P<0.001) and Step 2 CK (R=0.542, P<0.001). After correcting for gender, institution, and test-taking ability (using MCAT scores as a proxy for test-taking ability) in a hierarchical multiple regression model, Step 1 and Step 2 CK scores together explained 22.2% of the variance in count of honors grades. Conclusion: USMLE Step 1 and Step 2 CK scores moderately correlate with the number of honors grades per student in core clinical clerkships. This relationship is maintained even after correcting for gender, institution, and test-taking ability. These results indicate that USMLE scores have a positive linear association with clinical performance as a medical student.
10.2147/AMEP.S192011
pubmed_1053_8782
Using ELISA, we studied anti-PPD antibody values in 31 tuberculous and 39 carcinomatous pleural effusions. Mean ODI values of anti-PPD IgG, IgA and IgM antibodies in tuberculous pleural effusions were higher than those in carcinomatous pleural effusions (p less than 0.01 in IgG and IgA, p less than 0.05 in IgM antibodies). We also analyzed the detected antigens in PPD and BCG whole cell fraction recognized by IgG antibody in tuberculous pleural effusions. Among heteromolecular components, the antigen band from 25 to 40 Kd region was most frequently stained. This antigen was heat-stable, contained sugar components, and included no disulfide bonds.
10.1378/chest.97.3.670
pubmed_578_3278
BACKGROUND Various pattern-based methods exist that use in vitro or in silico affinity profiles for classification and functional examination of proteins. Nevertheless, the connection between the protein affinity profiles and the structural characteristics of the binding sites is still unclear. Our aim was to investigate the association between virtual drug screening results (calculated binding free energy values) and the geometry of protein binding sites. Molecular Affinity Fingerprints (MAFs) were determined for 154 proteins based on their molecular docking energy results for 1,255 FDA-approved drugs. Protein binding site geometries were characterized by 420 PocketPicker descriptors. The basic underlying component structure of MAFs and binding site geometries, respectively, were examined by principal component analysis; association between principal components extracted from these two sets of variables was then investigated by canonical correlation and redundancy analyses. RESULTS PCA analysis of the MAF variables provided 30 factors which explained 71.4% of the total variance of the energy values while 13 factors were obtained from the PocketPicker descriptors which cumulatively explained 94.1% of the total variance. Canonical correlation analysis resulted in 3 statistically significant canonical factor pairs with correlation values of 0.87, 0.84 and 0.77, respectively. Redundancy analysis indicated that PocketPicker descriptor factors explain 6.9% of the variance of the MAF factor set while MAF factors explain 15.9% of the total variance of PocketPicker descriptor factors. Based on the salient structures of the factor pairs, we identified a clear-cut association between the shape and bulkiness of the drug molecules and the protein binding site descriptors. CONCLUSIONS This is the first study to investigate complex multivariate associations between affinity profiles and the geometric properties of protein binding sites. We found that, except for few specific cases, the shapes of the binding pockets have relatively low weights in the determination of the affinity profiles of proteins. Since the MAF profile is closely related to the target specificity of ligand binding sites we can conclude that the shape of the binding site is not a pivotal factor in selecting drug targets. Nonetheless, based on strong specific associations between certain MAF profiles and specific geometric descriptors we identified, the shapes of the binding sites do have a crucial role in virtual drug design for certain drug categories, including morphine derivatives, benzodiazepines, barbiturates and antihistamines.
10.1186/1472-6807-10-32
pubmed_1031_12024
Previous studies addressing the role of the transcription factor cAMP response element-binding protein (CREB) in mammalian long-term synaptic plasticity and memory by gene targeting were compromised by incomplete deletion of the CREB isoforms. Therefore, we generated conditional knock-out strains with a marked reduction or complete deletion of all CREB isoforms in the hippocampus. In these strains, no deficits could be detected in lasting forms of hippocampal long-term potentiation (LTP) and long-term depression (LTD). When tested for hippocampus-dependent learning, mutants showed normal context-dependent fear conditioning. Water maze learning was impaired during the early stages, but many mutants showed satisfactory scores in probe trials thought to measure hippocampus-dependent spatial memory. However, conditioned taste aversion learning, a putatively hippocampus-independent memory test, was markedly impaired. Our data indicate that in the adult mouse brain, loss of CREB neither prevents learning nor substantially affects performance in some hippocampus-dependent tasks. Furthermore, it spares LTP and LTD in paradigms that are sensitive enough to detect deficits in other mutants. This implies either a species-specific or regionally restricted role of CREB in the brain and/or a compensatory upregulation of the cAMP response element modulator (CREM) and other as yet unidentified transcription factors.
pubmed_1031_12024
pubmed_50_8594
In recent decades, considerable research attention has been devoted to new synthetic procedures for thiacyclophanes. Thiacyclophanes are widely used as host molecules for the molecular recognition of organic compounds as well as metals. Herein, we report the selective and high-yielding synthesis of novel alternate-linked-meta-para-thiacyclophanes. These novel thiacyclophanes are selectively synthesized in high-yielding procedures. Furthermore, post-functionalization of the phenolic moieties was successfully performed. The 3D structure of the alternate-linked-meta-para-[22.12]thiacyclophane was further elucidated via X-ray crystallographic analysis.
10.3762/bjoc.14.192
pubmed_540_7778
Epizootic lymphangitis (EZL) is a chronic, contagious disease of equids caused by the fungus Histoplasma capsulatum var. farciminosum. The disease is often prevalent in cart pulling equids in developing countries. This study was undertaken in Central and South Gondar zones of Amhara region, Ethiopia with the objectives of estimating the prevalence of EZL in cart pulling horses and mules and identifying the risk factors of the disease. Two towns, one high altitude and one mid altitude, from each of the two zones were included for the study. A total of 528 cart pulling horses and mules from the selected towns were examined clinically, screened by physical examination based on clinical signs of the disease and confirmed by microscopic mycological examination of the causative agent. Potential risk factors data were collected through observation of cart animals and interviewing of cart owners and were statistically evaluated using mixed effect logistic regression. An overall EZL prevalence of 12.5% (95% CI: 9.9-15.6%) was found. The prevalence was 19.9% (95% CI: 15.8-24.8%) in horses and 5.8% (95% CI: 2.4-13.2%) in mules. The disease was prevalent in mid altitude towns but was not detected in high altitude cold towns of the study zones. The risk factor analysis revealed that sharing of harness, mingling of cart animals in cart stations, communal housing and pre-existing trauma wound were risk factors of EZL in cart pulling horses and mules. The study generally indicated that EZL is a prevalent problem in mid altitude towns that endangers the livelihood of the cart owners and wellbeing of cart pulling equids. This warrants the initiation of a control strategy mainly focusing on improving management of cart pulling equids related to the identified risk factors to ameliorate the EZL problem in the study area.
10.1016/j.heliyon.2022.e09939
pubmed_482_5834
Protein misfolding induced by missense mutations is the source of hundreds of conformational diseases. The cell quality control may eliminate nascent misfolded proteins, such as enzymes, and a pathological loss-of-function may result from their early degradation. Since the proof of concept in the 2000s, the bioinspired pharmacological chaperone therapy became a relevant low-molecular-weight compound strategy against conformational diseases. The first-generation pharmacological chaperones were competitive inhibitors of mutant enzymes. Counterintuitively, in binding to the active site, these inhibitors stabilize the proper folding of the mutated protein and partially rescue its cellular function. The main limitation of the first-generation pharmacological chaperones lies in the balance between enzyme activity enhancement and inhibition. Recent research efforts were directed towards the development of promising second-generation pharmacological chaperones. These non-inhibitory ligands, targeting previously unknown binding pockets, limit the risk of adverse enzymatic inhibition. Their pharmacophore identification is however challenging and likely requires a massive screening-based approach. This review focuses on second-generation chaperones designed to restore the cellular activity of misfolded enzymes. It intends to highlight, for a selected set of rare inherited metabolic disorders, the strategies implemented to identify and develop these pharmacologically relevant small organic molecules as potential drug candidates.
10.3390/molecules25143145
pubmed_170_19010
In 2006, Cell Cycle featured the concept that aging is not caused by molecular damage (nor by free radicals) but instead is a purposeless quasi-program (program-like, but not a program) driven in part by TOR (Target of Rapamycin). Taken together with the analysis of clinical data, this pointed to Sirolimus (rapamycin) as a genuine anti-aging drug which will prolong life in humans and prevent age-related diseases by slowing down aging. Since that time many predictions of this concept have been confirmed. Rapamycin was shown to suppress aging in mammalian cells, prolong life span in mice and flies, improve immunity and stem cell function in old animals, thus confirming twelve predictions as discussed herein. One prediction remains to be confirmed: rapamycin will become the cornerstone of anti-aging therapy in our life time.
10.4161/cc.9.10.11872
pubmed_997_12523
Wasabi (Eutrema japonicum), also known as Japanese horseradish, is a perennial herb widely used in Japanese cuisine for its special flavour. The health-promoting phytochemicals and antioxidant capacity of four organs (leaf, petiole, rhizome, and root) of two cultivars (Chuankui-1 and Chuankui-2) of wasabi from two producing areas, Leibo and Guangyuan in Sichuan Province, China, were investigated in this study. The results showed that leaves were rich in pigments, soluble protein, ascorbic acid, and total phenolics and had the highest antioxidant capacity. Soluble sugars were highest in the petioles and were 1.1- to 5-fold higher than those in the other three organs. Glucosinolates and glucosinolate breakdown products (GBPs) were the most abundant in rhizomes, and their maximum values were 271.61 mmol kg-1 DW and 249.78 mmol kg-1 DW, respectively. The rhizomes of Chuankui-1 in Leibo and the leaves of Chuankui-1 in Guangyuan were superior in terms of glucosinolates and GBPs. These findings provide new insights that will aid the use of wasabi cultivars; they also have implications for the environmental characteristics needed to obtain better quality wasabi products. In the future, metabolome and transcriptome can be used to analyze the potential mechanism of differences among typical varieties, origins and parts.
10.3389/fpls.2022.1043378
pubmed_517_18093
BACKGROUND Workplace violence (WPV) is an occupational health hazard in both low and high income countries. To design WPV prevention programs, prior knowledge and understanding of conditions in the targeted population are essential. This study explores and describes the views of drivers and conductors on the causes of WPV and ways of preventing it in the road passenger transport sector in Maputo City, Mozambique. METHODS The design was qualitative. Participants were purposefully selected from among transport workers identified as victims of WPV in an earlier quantitative study, and with six or more years of experience in the transport sector. Data were collected in semi-structured interviews. Seven open questions covered individual views on causes of WPV and its prevention, based on the interviewees' experiences of violence while on duty. Thirty-two transport professionals were interviewed. The data were analyzed by means of qualitative content analysis. RESULTS The triggers and causes of violence included fare evasion, disputes over revenue owing to owners, alcohol abuse, overcrowded vehicles, and unfair competition for passengers. Failures to meet passenger expectations, e.g. by-passing parts of a bus route or missing stops, were also important. There was disrespect on the part of transport workers, e.g. being rude to passengers and jumping of queues at taxi ranks, and there were also robberies. Proposals for prevention included: training for workers on conflict resolution, and for employers on passenger-transport administration; and, promoting learning among passengers and workers on how to behave when traveling collectively. Regarding control and supervision, there were expressed needs for the recording of mileage, and for the sanctioning of workers who transgress queuing rules at taxi ranks. The police or supervisors should prevent drunken passengers from getting into vehicles, and drivers should refuse to go to dangerous, secluded neighborhoods. Finally, there is a need for an institution to judge alleged cases of employees not handing over demanded revenues to their employer. CONCLUSIONS The causes of WPV lie in problems regarding money, behavior, environment, organization and crime. Suggestions for prevention include education, control to avoid critical situations, and a judicial system to assess malpractices. Further research in the road passenger transport sector in Maputo City, Mozambique and similar settings is warranted.
10.1186/1471-2458-11-800
pubmed_27_7555
The aims of our study were (1) to describe the ultrasonographic findings of the injured medial collateral ligament of the knee and (2) to assess the usefulness of ultrasonography in both evaluating the presence and location of the medial collateral ligament injuries and predicting the prognoses for the patients. The study group consisted of 16 patients with the clinical diagnosis of medial collateral ligament injury. We also examined 20 knee joints in 10 volunteers who had no history of injury to the knee. To predict prognoses, we divided the patients into two groups on the basis of the location of medial collateral ligament injuries. A thickened and heterogeneously hypoechoic appearance of the medial collateral ligament was considered abnormal. The normal medial collateral ligament was a thin and moderately homogeneous hypoechoic band with an average thickness of 4.3 mm (range, 3.3 to 5.6 mm) at the femoral attachment and of 2.3 mm (range, 1.3 to 3.2 mm) at the tibial attachment. All injured medial collateral ligament structures were thickened and heterogeneously hypoechoic. According to the criteria for grading of medial collateral ligament injury with stress view, 10 patients had grade III medial collateral ligament tears, three had grade II tears, and none had grade I injuries. In 15 (94%) of 19 knees, a correct diagnosis could be made with ultrasonography. Ultrasonography is useful in evaluating isolated medial collateral ligament injuries and in predicting patient outcome on the basis of the location of the medial collateral ligament injuries.
10.7863/jum.1996.15.9.621
pubmed_1032_10466
The aims of this study were to review the psychometric properties of the widely used Pain Catastrophizing Scale (PCS) using meta-analytic methods and to investigate the relationship between PCS scores and participant characteristics. A systematic search from 1995 found 229 experimental, quasi-experimental, and correlational studies that report PCS scores. Multivariate regression explored variables related to pain catastrophizing and participant demographics. Across studies, good internal reliability (α = 0.92, 95% confidence interval 0.91-0.93) and test-retest reliability scores (Spearman ρ = 0.88, 95% confidence interval 0.83-0.93) were found for PCS total scores but not for subscales. Pain Catastrophizing Scale scores were unrelated to age or sex, but strongly related to participants' pain type, highest in those with generalized pain. Language of the PCS also affected PCS scores, with further research necessary to determine linguistic, cultural, or methodological (eg, sampling strategy) influences. Study type influenced PCS scores with nonrandomized controlled trials reporting higher PCS scores than other study types, but results were confounded with pain diagnosis, as controlled trials were more likely than quasi-experimental studies to recruit clinical samples. The meta-analytic results provide insights into demographic influences on pain catastrophizing scores and highlight areas for further research. The advantages of systematic review and meta-analytic methods to achieve greater understanding and precision of psychometric properties-in this case, of the PCS-are applicable to other widely used outcome tools.
10.1097/j.pain.0000000000001494
pubmed_815_11835
1. A rapid solution-changing system using a solenoid was set up. The half-time for changing the external solution surrounding a ventricular cardiac cell was 7.2 +/- 1.4 ms, whereas the time needed to change 90% of this solution was 48.5 +/- 7.9 ms. This rapid switching system was used to reduce the external sodium concentration at different moments during the action potential (recorded using the whole-cell method) to 50% of its original value. This was performed in order to investigate the effect on the shape and duration of the action potential of modifying the activity of the sodium-calcium exchanger. 2. A diminution of the action potential duration was seen irrespective of the substitute used for reducing the NaCl concentration from 140 to 70 mM. The magnitude of this diminution depended on the presence or absence of EGTA (5 mM) in the pipette solution and also on the moment during the action potential at which the NaCl substitution occurred. 3. Some differences were observed depending on whether the NaCl substitute used was lithium chloride or choline chloride. When choline chloride or N-methyl-D-glucamine was used as the NaCl substitute, the amplitude of the action potential was slightly reduced (by 2-5 mV) when the solution was changed 40 ms before the action potential was triggered. This reduction was never observed when LiCl was used as the NaCl substitute. 4. The effects on the shape of the action potential of changing from a solution containing 140 mM NaCl to one containing 70 mM NaCl and 70 mM LiCl were much more rapid when these changes occurred at a later stage during the action potential. The rate of repolarization was more than doubled when the change occurred at a late stage of the action potential but was hardly changed at the beginning of the plateau. 5. These experiments confirm the role of the sodium-calcium exchange current in determining the duration of the mammalian ventricular action potential. However, it is also possible that the sodium background current plays a significant role in determining the shape of the action potential.
10.1113/jphysiol.1994.sp020268
pubmed_916_10320
UNLABELLED The proliferation and trafficking of T lymphocytes in immune responses are crucial events in determining inflammatory responses. To study whole-body T lymphocyte dynamics noninvasively in vivo, we generated anti-CD4 and -CD8 cys-diabodies (cDbs) derived from the parental antibody hybridomas GK1.5 and 2.43, respectively, for (89)Zr-immuno-PET detection of helper and cytotoxic T cell populations. METHODS Anti-CD4 and -CD8 cDbs were engineered, produced via mammalian expression, purified using immobilized metal affinity chromatography, and characterized for T cell binding. The cDbs were site-specifically conjugated to maleimide-desferrioxamine for (89)Zr radiolabeling and subsequent small-animal PET/CT acquisition and ex vivo biodistribution in both wild-type mice and a model of hematopoietic stem cell (HSC) transplantation. RESULTS Immuno-PET and biodistribution studies demonstrate targeting and visualization of CD4 and CD8 T cell populations in vivo in the spleen and lymph nodes of wild-type mice, with specificity confirmed through in vivo blocking and depletion studies. Subsequently, a murine model of HSC transplantation demonstrated successful in vivo detection of T cell repopulation at 2, 4, and 8 wk after HSC transplantation using the (89)Zr-radiolabeled anti-CD4 and -CD8 cDbs. CONCLUSION These newly developed anti-CD4 and -CD8 immuno-PET reagents represent a powerful resource to monitor T cell expansion, localization, and novel engraftment protocols. Future potential applications of T cell-targeted immuno-PET include monitoring immune cell subsets in response to immunotherapy, autoimmunity, and lymphoproliferative disorders, contributing overall to preclinical immune cell monitoring.
10.2967/jnumed.114.153338
pubmed_508_22028
The serotoninergic pathways are possible targets for the action of lithium, a therapeutic agent for treatment of bipolar affective disorders. This study aimed to investigate the molecular mechanisms regulating human serotonin transporter gene (SLC6A4) expression by lithium and, specifically, the role of the variable number tandem repeat (VNTR) polymorphic region in intron 2, which is potentially a predisposing genetic factor for bipolar affective disorders. We demonstrated that addition of lithium to human JAr cells led to changes in the levels of SLC6A4 mRNA and protein. Additional investigations revealed that the intron 2 VNTR domain was a potential target for mediation of a transcriptional response to lithium. Properties of two transcription factors, CCCTC binding protein (CTCF) and Y-box binding protein 1 (YB-1), previously shown to be involved in the regulation of SLC6A4 VNTR, were found to be modulated by LiCl. Thus, levels of CTCF and YB-1 mRNA and protein were altered in vivo in response to LiCl. Furthermore, CTCF and YB-1 showed differential binding to the polymorphic alleles of the VNTR on exposure to LiCl. Our data suggest a model in which differential binding of CTCF and YB-1 to the allelic variants of the intron 2 VNTR can be regulated by lithium and in part result in differential and even aberrant expression of SLC6A4. Our study of the regulation of the SLC6A4 VNTR by lithium may improve the understanding of psychiatric disorders and enable the development of novel therapies for conditions such as bipolar affective disorder to target only the at-risk allele.
10.1523/JNEUROSCI.0892-06.2007
pubmed_979_6485
The time- and concentration-dependent effects of ricin on some biomarkers of cellular toxicity, including production of superoxide anion (O2-), nitric oxide (NO), and DNA single strand breaks (SSB), as well as cellular death, have been examined in the J774A.1 macrophage cell cultures. Various concentrations of ricin have been added to various cell cultures, and the cells were incubated for 12, 24, 36, and 48 hours. Following 12 hour incubation, ricin did not cause significant increases in any of those biomarkers. However, time- and concentration-dependent increases were observed in the induction of all the biomarkers after incubation for 24-48 hours. Approximately twofold increases in the production of O2- were observed after incubation with 1 and 10 ng/mL of ricin for 24 and 36-48 hours, respectively. The concentrations of ricin that caused approximately twofold increases in the rate of DNA-SSB are 10 and 1-10 ng/mL after 24 and 36-48 hours incubation, respectively. Approximately twofold increases in NO production were only observed after incubation of the cultures with 1-10 ng/mL of ricin for 36-48 hours. Fifty percent reductions in cellular viability were also observed with ricin concentrations of 10-100, 10, and 1-10 ng/mL, after incubation for 24, 36, and 48 hours, respectively.
10.1002/(sici)1099-0461(1999)13:3/4<179::aid-jbt8>3.0.co;2-4
pubmed_1135_10460
BACKGROUND Kazakhstan, a developing middle-income country, has the highest road traffic collision (RTC) mortality in the European Region. The aims of this study were to determine main characteristics of road traffic fatalities in Semey region, Kazakhstan and to compare findings with National data and middle-income European countries. METHODS This descriptive surveillance study assesses RTC mortality rates and epidemiology in the Semey Region of East Kazakhstan Oblast. Data of all 318 road traffic fatalities form the Semey Regional Center for Forensic Medicine were analyzed for the 5-year period of January 1, 2006 through December 31, 2010. RESULTS Over the study period, the average road traffic mortality in the Semey Region was 12.1 per 100,000 population with downward trend by 35.1% (p=0.002). The victims mean age was 37.1 (SD=17) years. Males predominated at 74.5%. Vehicle fatality was the most common mode of fatality at 61.3%. The majority of collisions, 53.1%, occurred on highways. Most victims, 67.3%, have died at the scene of collision; in 67.3% of fatalities, autopsies identified multiple injuries as cause of death. The high number of fatal collisions took place in "no snow" season (P<0.001), with an overall 5-years downward dynamic. CONCLUSION High proportion of males, pedestrians and car occupants among road traffic fatalities; high proportion of death on scene in case of highway collisions are specifics for Semey region, Kazakhstan. These findings can be used to formulate preventive strategies to reduce fatalities and to improve the medical care system for road traffic fatalities.
pubmed_1135_10460
pubmed_1039_6286
The molecular sieving property of human erythrocyte membrane in slightly hypotonic media has been utilized for studying the intracellular localization of some proteins (Cseke et al., 1978, FEBS Lett. 96 15-18). It is now shown that four proteins which appear to be uniformly distributed within the cell behave similarly irrespective of the membrane resistance differences caused by changes of temperature and metabolic energy supply. Five enzymes catalyzing consecutive reactions in the glycolytic pathway between triosephosphate formation and lactate production are released from erythrocytes in quantities deviating from those predicted on the basis of molecular sieving. The data are compatible with the assumption that these enzymes form complexes with each other under in vivo conditions and that complex formation is facilitated if glycolysis is working at high rate (37 degrees C).
pubmed_1039_6286
pubmed_794_11987
Photobiomodulation therapy (PBMT) has been used to treat patients with chronic neck and/or shoulder pain. However, it is unknown whether the concurrent use of PBMT and static magnetic field (PBMT-sMF) also has positive effects in these patients. The aim of this study was to investigate the effects of PBMT-sMF versus placebo on pain intensity, range of motion (ROM) and treatment satisfaction in patients with chronic nonspecific neck and/or shoulder pain. A randomized controlled trial, with blinded assessors, therapists and patients was carried out. Seventy-two patients with chronic nonspecific neck and/or shoulder pain were randomized to either active PBMT-sMF (n = 36) or placebo PBMT-sMF (n = 36). Patients were treated twice weekly, over 3 weeks. Primary outcome was pain intensity, measured 15 min after the last treatment session and at 24-, 48-, 72-h, and 7-days after the last treatment. Secondary outcomes were ROM, patient' treatment satisfaction, and adverse effects. PBMT-sMF was able to reduce pain intensity in all time points tested compared to placebo (p &lt; 0.05). There was no difference between groups in the secondary outcomes (p &gt; 0.05). Our results suggest that PBMT-sMF is better than placebo to reduce pain in patients with chronic nonspecific neck and/or shoulder pain at short-term.
10.3390/life12050656
pubmed_948_11113
A prospective, double-blind, randomized, single-center study was conducted to compare ursodeoxycholic acid alone with the combination of ursodeoxycholic acid and chenodeoxycholic acid for dissolution therapy of gallstone fragments after shock wave lithotripsy. Patients with single radiolucent gallstones up to 30 mm in diameter or up to three stones of similar total volume received either 750 mg ursodeoxycholic acid alone (group A, n = 138) or the combination of 500 mg ursodeoxycholic acid and 500 mg chenodeoxycholic acid (group B, n = 144) in a single bedtime dose. The bile acids were administered from 2 wk before electrohydraulic lithotripsy until 3 mo beyond complete disappearance of all fragments. Patient's characteristics, stones (group A, 82% single stones, maximum diameter 19 +/- 5 mm, mean +/- S.D.; group B, 82% single stones, 18 +/- 5 mm), lithotripsy treatment and follow-up period were not different between the two groups. Between the two groups, no statistically significant difference was found in the time required for complete clearance of the fragments (group A, median time = 15 mo; group B, median time = 13 mo; p = 0.7). At 12 mo after lithotripsy, the probability of complete clearance was 46% +/- 5% in group A and 49% +/- 5% in group B. Diarrhea occurred significantly more often in group B than in group A (p less than 0.001) and was the main reason for withdrawal of randomized medication. Severe adverse effects of the bile acids were not observed. It is concluded that monotherapy with ursodeoxycholic acid is as efficient as the combination of ursodeoxycholic acid and chenodeoxycholic acid for fragment dissolution after lithotripsy.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed_948_11113
pubmed_120_706
Designed as a new group of planar molecule containing the proposed 2-phenylnaphthalene-type structure, a number of 11H-indolo[3.2-c]quinoline derivatives were synthesized and evaluated biologically. Several compounds were found to possess cytotoxic activity against the growth of human promyelocytic leukemia cells (HL-60), against the small cell lung cancer (SCLC), and showed good response in the National Cancer Institute preclinical antitumor drug discovery 60-cell line panel.
10.1016/s0223-5234(02)01420-4
pubmed_666_4525
OBJECTIVE To explore preferences for self-management and support services in patients with inflammatory joint disease (IJD) and to investigate whether these preferences differ by age, sex, diagnosis, and disease duration. METHODS We used a nationwide cross-sectional online survey for patients with rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis. Descriptive statistics were applied to explore preferences and to test for differences according to the different subgroups of patients. RESULTS The questionnaire was completed by 664 patients. Younger patients indicated greater interest in 1-to-1 discussions with psychologists or another patient, educational sessions, events, and online services, and older patients indicated greater interest in talks by researchers. More women than men indicated interest in health professionals' 1-to-1 discussions, occupational therapists' question-and-answer (Q and A) sessions, physical activity, and informational websites. Patients with axial spondyloarthritis tended to indicate the most interest in the different services, and patients with rheumatoid arthritis the least interest, reaching statistical significance regarding discussion groups about IJD experiences, 1-to-1 discussions with psychologists or another patient, Q and A with another patient, stress/anger management, and online patient communication. More patients with short rather than long disease duration indicated interest in 1-to-1 discussions with rheumatologists or nurses, organized talks with experienced patients, and online services for patient communication and stories. CONCLUSION Patients with IJD report various needs regarding self-management and support services, including 1-to-1 services traditionally delivered as part of usual care, but also talks, physical activity, and educational and online services. Although preferences differed across age, sex, diagnosis, and disease duration, all subgroups indicated great need for support, with only small differences in their top preferences.
10.1002/acr.24344
pubmed_695_13627
Members of the trochoidean genus Margarella (Calliostomatidae) are broadly distributed across Antarctic and sub-Antarctic ecosystems. Here we used novel mitochondrial and nuclear gene sequences to clarify species boundaries and phylogenetic relationships among seven nominal species distributed on either side of the Antarctic Polar Front (APF). Molecular reconstructions and species-delimitation analyses recognized only four species: M. antarctica (the Antarctic Peninsula), M. achilles (endemic to South Georgia), M. steineni (South Georgia and Crozet Island) and the morphologically variable M. violacea (=M. expansa, M. porcellana and M. pruinosa), with populations in southern South America, the Falkland/Malvinas, Crozet and Kerguelen Islands. Margarella violacea and M. achilles are sister species, closely related to M. steineni, with M. antarctica sister to all these. This taxonomy reflects contrasting biogeographic patterns on either side of the APF in the Southern Ocean. Populations of Margarella north of the APF (M. violacea) showed significant genetic variation but with many shared haplotypes between geographically distant populations. By contrast, populations south of the APF (M. antarctica, M. steineni and M. achilles) exhibited fewer haplotypes and comprised three distinct species, each occurring across a separate geographical range. We hypothesize that the biogeographical differences may be the consequence of the presence north of the APF of buoyant kelps - potential long-distance dispersal vectors for these vetigastropods with benthic-protected development - and their near-absence to the south. Finally, we suggest that the low levels of genetic diversity within higher-latitude Margarella reflect the impact of Quaternary glacial cycles that exterminated local populations during their maxima.
10.1016/j.ympev.2020.107039
pubmed_542_9186
Acetylcholine can be released from parasympathetic nerve endings in rat atria by 57 mM K+ depolarization or by electrical field stimulation. We have studied the presynaptic modulation of [3H]acetylcholine release from superfused rat atria prelabeled with [3H]choline. Exogenous acetylcholine and the specific muscarinic agonist oxotremorine inhibit the stimulation-induced overflow of [3H]acetylcholine into the superfusion medium. The half-maximal inhibitory concentration (IC50) of oxotremorine is 0.3 microM. The cholinesterase inhibitor neostigmine also decreases K+-stimulated [3H]acetylcholine overflow, whereas the muscarinic antagonist atropine enhances the overflow of [3H]acetylcholine. These data suggest that acetylcholine release in atria is modulated through negative feedback by the endogenous transmitter. The sympathetic adrenergic neurotransmitter norepinephrine and the neurohormone epinephrine also inhibit the overflow of [3H]acetylcholine by approximately 60%. The IC50 values for the inhibitory effects of these catecholamines are 6.3 and 2.2 microM, respectively. The inhibitory effect of norepinephrine is blocked by the alpha-adrenergic receptor antagonist yohimbine but not by the beta-adrenergic receptor antagonist propranolol. We suggest that presynaptic muscarinic and alpha-adrenergic receptors participate in the physiological and pharmacological control of cardiac parasympathetic activity.
10.1152/ajpheart.1985.248.1.H33
pubmed_21_6226
Symptomatic oral infection with Candida albicans is characterized by invasion of the oral epithelium by virulent hyphae that cause tissue damage releasing the inflammatory mediators that initiate and sustain local inflammation. Candida albicans triggers pattern-recognition receptors of keratinocytes, macrophages, monocytes and dendritic cells, stimulating the production of IL-1β, IL-6 and IL-23. These cytokines induce the differentiation of Th17 cells and the generation of IL-17- and/or IL-22-mediated antifungal protective immuno-inflammatory responses in infected mucosa. Some immune cells including NKT cells, γδ T cells and lymphoid cells that are innate to the oral mucosa have the capacity to produce large quantities of IL-17 in response to C. albicans, sufficient to mediate effective protective immunity against C. albicans. On the other hand, molecular structures of commensal C. albicans blastoconidia, although detected by pattern-recognition receptors, are avirulent, do not invade the oral epithelium, do not elicit inflammatory responses in a healthy host, but induce regulatory immune responses that maintain tissue tolerance to the commensal fungi. The type, specificity and sensitivity of the protective immune response towards C. albicans is determined by the outcome of the integrated interactions between the intracellular signalling pathways of specific combinations of activated pattern-recognition receptors (TLR2, TLR4, Dectin-1 and Dectin-2). IL-17-mediated protective immune response is essential for oral mucosal immunity to C. albicans infection.
10.1111/jop.12120
pubmed_21_23390
AIM In the TELEDIAB-1 study, the Diabeo system (a smartphone coupled to a website) improved HbA1c by 0.9% vs controls in patients with chronic, poorly controlled type 1 diabetes. The system provided two main functions: automated advice on the insulin doses required; and remote monitoring by teleconsultation. The question is: how much did each function contribute to the improvement in HbA1c? METHODS Each patient received a smartphone with an insulin dose advisor (IDA) and with (G3 group) or without (G2 group) the telemonitoring/teleconsultation function. Patients were classified as "high users" if the proportion of "informed" meals using the IDA exceeded 67% (median) and as "low users" if not. Also analyzed was the respective impact of the IDA function and teleconsultations on the final HbA1c levels. RESULTS Among the high users, the proportion of informed meals remained stable from baseline to the end of the study 6months later (from 78.1±21.5% to 73.8±25.1%; P=0.107), but decreased in the low users (from 36.6±29.4% to 26.7±28.4%; P=0.005). As expected, HbA1c improved in high users from 8.7% [range: 8.3-9.2%] to 8.2% [range: 7.8-8.7%] in patients with (n=26) vs without (n=30) the benefit of telemonitoring/teleconsultation (-0.49±0.60% vs -0.52±0.73%, respectively; P=0.879). However, although HbA1c also improved in low users from 9.0% [8.5-10.1] to 8.5% [7.9-9.6], those receiving support via teleconsultation tended to show greater improvement than the others (-0.93±0.97 vs -0.46±1.05, respectively; P=0.084). CONCLUSION The Diabeo system improved glycaemic control in both high and low users who avidly used the IDA function, while the greatest improvement was seen in the low users who had the motivational support of teleconsultations.
10.1016/j.diabet.2013.09.001
pubmed_821_4263
S100 proteins are a family of 10-14 kDa EF-hand-containing calcium binding proteins that function to transmit calcium-dependent cell regulatory signals. S100 proteins have no intrinsic enzyme activity but bind in a calcium-dependent manner to target proteins to modulate target protein function. Transglutaminases are enzymes that catalyze the formation of covalent epsilon-(gamma-glutamyl)lysine bonds between protein-bound glutamine and lysine residues. In the present study we show that transglutaminase-dependent covalent modification is a property shared by several S100 proteins and that both type I and type II transglutaminases can modify S100 proteins. We further show that the reactive regions are at the solvent-exposed amino- and carboxyl-terminal ends of the protein, regions that specify S100 protein function. We suggest that transglutaminase-dependent modification is a general mechanism designed to regulate S100 protein function.
10.1021/bi0019747
pubmed_976_6435
Protein structure prediction by comparative modeling benefits greatly from the use of multiple sequence alignment information to improve the accuracy of structural template identification and the alignment of target sequences to structural templates. Unfortunately, this benefit is limited to those protein sequences for which at least several natural sequence homologues exist. We show here that the use of large diverse alignments of computationally designed protein sequences confers many of the same benefits as natural sequences in identifying structural templates for comparative modeling targets. A large-scale massively parallelized application of an all-atom protein design algorithm, including a simple model of peptide backbone flexibility, has allowed us to generate 500 diverse, non-native, high-quality sequences for each of 264 protein structures in our test set. PSI-BLAST searches using the sequence profiles generated from the designed sequences ("reverse" BLAST searches) give near-perfect accuracy in identifying true structural homologues of the parent structure, with 54% coverage. In 41 of 49 genomes scanned using reverse BLAST searches, at least one novel structural template (not found by the standard method of PSI-BLAST against PDB) is identified. Further improvements in coverage, through optimizing the scoring function used to design sequences and continued application to new protein structures beyond the test set, will allow this method to mature into a useful strategy for identifying distantly related structural templates.
10.1002/prot.10346
pubmed_425_22137
OBJECTIVE To examine whether diets involving reduced chewing affect the degree of cerumen impaction in older people in residential care. METHODS A total of 51 people (53% male) over 65 years (80.5 ± 9.3) were recruited from two residential aged care facilities in Perth, Australia. Participants were classified as "chewers" (on unrestricted or soft food diets), or "non-chewers" (on pureed or nil by mouth diets), and completed a survey about predisposing factors for cerumen impaction. Otoscopy and tympanometry were used to assess cerumen impaction and ear canal occlusion. Participants with excess cerumen were referred for wax removal. RESULTS No significant difference in cerumen accumulation was found between groups. However, 57% of participants showed excess cerumen requiring removal. CONCLUSION Diets involving reduced chewing are not associated with increased cerumen in older people in residential care. The prevalence of cerumen impaction is high in this population, and improved cerumen screening and management is needed in residential aged care.
10.1111/ajag.12736
pubmed_672_13564
IL-1 and TNF-alpha are induced in macrophages by LPS; however, it is unclear whether similar mechanisms control the expression of both genes. Here, we report on the detection of differential regulation of LPS induced IL-1 and TNF-alpha mRNA expression and protein production in murine macrophages based on the use of inhibitors of second messenger pathways. Northern blot analysis was performed with total RNA obtained from murine (C57Bl/6) peritoneal macrophages stimulated in vitro with LPS with or without an inhibitor of protein kinase C (PKc)(1-(5-isoquinolinesulfonyl)-2-methylpiperazine hydrochloride; H7) or an inhibitor of calmodulin (CaM)-dependent kinase (N-(6-amino-hexyl)-5-chloro-1-naphthalene-sulfonamide hydrochloride; W7). Northerns were analyzed with probes for IL-1 alpha and IL-1 beta and TNF-alpha. The expression of the three cytokine mRNA by LPS was inhibited in a dose response manner by H7. In contrast, the expression of IL-1 mRNA, but not TNF-alpha mRNA, was blocked by treatment with W7. Parallel studies monitoring biologic activities of these two cytokines confirm the mRNA data. PKc inhibitors, H7 and retinal, block both IL-1 and TNF-alpha protein production and inhibitors of CaM kinase, W7, N-(6-aminobutyl)-5-chloro-2-naphthalenesulfonamide, calmidazolum, and trifluoperazine dichloride inhibit only IL-1 production. These data suggest that both PKc and CaM kinase dependent pathways are involved in the induction of IL-1 mRNA by LPS. In contrast, TNF-alpha expression appears to be PKc dependent but not CaM kinase dependent.
pubmed_672_13564
pubmed_1090_12183
Maintaining fertility and having children after treatment for breast cancer are a growing concern for women of childbearing age. There are many factors to be considered before a decision can be made. This article reviews the changes in breast cancer survival and treatment, epidemiology of pregnancy after breast cancer, and concerns during and after the pregnancy period. Specific nursing interventions aimed at improving quality of life and surviving illness are described.
pubmed_1090_12183
pubmed_34_7621
Two studies examined how the relevance of group identity influences two psychological mechanisms of collective action: Emotion- and problem-focused coping with collective disadvantage. Extending Van Zomeren, Spears, Fischer, and Leach's (2004) integrative theoretical model of coping with collective disadvantage, we predicted that when group identity is more relevant to disadvantaged group members, it increases their collective action tendencies through their feelings of group-based anger about their group's disadvantage. When group identity is less relevant and hence emotion-focused coping processes are less likely, group-efficacy beliefs become more predictive of disadvantaged group members' collective action tendencies because people focus more instrumentally on whether collective action will be effective (and benefit them) or not. A field study and a follow-up experiment both showed that the relevance of group identity facilitated emotion-focused coping and moderated problem-focused coping with collective disadvantage. We discuss these results in terms of two distinct psychological mechanisms of collective action.
10.1348/014466607X231091
pubmed_1011_14829
Infection of monkey cells with human adenovirus (Ad) is abortive, but the infection can be enhanced by coinfecting with simian virus 40 (SV40). However, in the coinfected monkey cells, Ad interferes strongly with SV40 DNA biosynthesis. This interference was found to be a reproducible, delicately controlled phenomenon that was proportional to the multiplicity of infection of Ad and dependent on the active expression of the Ad genome. Newly synthesized SV40 DNA was not broken down in cells after delayed superinfection with Ad, and several early events of SV40 infection such as adsorption, penetration, uncoating, induction of cellular DNA synthesis, and enhancement of Ad infection were not markedly influenced by Ad-mediated interference. It is unlikely that interference is simply due to competition between SV40 and Ad for metabolites, enzymes, or replication sites. The interference effect could be partially neutralized by an increase in the multiplicity of coinfecting SV40 or by an increase in the time interval between SV40 infection and Ad coinfection. Interference was shown to be due to the activity of an Ad early gene product. However, the detailed mechanism of this Ad interference is still unclear.
10.1128/JVI.27.2.275-287.1978
pubmed_324_20027
BACKGROUND The increasing availability of molecular sequence data means that the accuracy of future phylogenetic studies is likely to by limited by systematic bias and taxon choice rather than by data. In order to take advantage of increasing datasets, user-friendly tools are required to facilitate phylogenetic analyses and to reduce duplication of dataset assembly efforts. Current phylogenetic pipelines are dependency-heavy and have significant technical barriers to use. RESULTS Here we present iPhy, a web application that lets non-technical users assemble, share and analyse DNA sequence datasets for multigene phylogenetic investigations. Built on a simple client-server architecture, iPhy eases the collection of gene sets for analysis, facilitates alignment and reliably generates phylogenetic analysis-ready data files. Phylogenetic trees generated in external programs can be imported and stored, and iPhy integrates with iTol to allow trees to be displayed with rich data annotation. The datasets collated in iPhy can be shared through the client interface. We show how systematic biases can be addressed by using explicit criteria when selecting sequences for analysis from a large dataset. A representative instance of iPhy can be accessed at iphy.bio.ed.ac.uk, but the toolkit can also be deployed on a local server for advanced users. CONCLUSIONS iPhy provides an easy-to-use environment for the assembly, analysis and sharing of large phylogenetic datasets, while encouraging best practices in terms of phylogenetic analysis and taxon selection.
10.1186/1471-2105-12-30
pubmed_579_24993
STUDY DESIGN Single-centre, retrospective cohort study. OBJECTIVES To analyse the return-to-work intentions during spinal cord injury (SCI) rehabilitation. SETTING Tertiary care, spinal cord injury rehabilitation unit, National Spinal Injuries Centre, Stoke Mandeville Hospital, Ayelsbury, UK. METHODS Employment outcomes were obtained from the Needs Assessment Checklist (NAC), for all patients admitted to the unit between February 2008 and October 2014. NAC1 is completed within 4 weeks post-mobilisation and NAC2 upon the patient moving to the pre-discharge ward. Data from 362 participants were analysed for return-to-work intentions, by gender, age and injury severity. RESULTS Seventy-six percent of the sample population was employed at the time of their injury. At NAC1, 22.4% of individuals had made plans to return to work, whereas 44.2% had not; at NAC2, 34.3% had made plans to return to work and 31.2% had not. This difference was found to be statistically significant. There were significant differences in return-to-work intentions by injury severity at NAC1 but not NAC2, and by age group at NAC2 but not NAC1. CONCLUSION Less than half of those employed at the time of their injury had made plans to return to work before their discharge from the unit. The low proportion of individuals with SCI returning to work--just one in three--is concerning in view of the lost health and psychosocial benefits, and requires greater prominence during rehabilitation. Future research into effective employment interventions to improve employment outcomes in this population is required.
10.1038/sc.2015.122
pubmed_868_19026
Fibrillary glomerulonephritis (FGN) is a rare disorder with poor renal prognosis. It is a heterogeneous disease associated with significant risk of end-stage renal disease (ESRD). Its etiology and pathogenesis have not been clearly identified. We report a case of a patient presenting with hypertensive crisis, nephrotic range proteinuria, and rapidly progressive glomerulonephritis (RPGN). The kidney biopsy demonstrates crescentic GN on light microscopy (LM) and strong pseudo-linear/globular glomerular basement membrane (GBM) staining for immunoglobulin G on immunofluorescence (IF), suggestive of anti-GBM disease. However, circulating anti-GBM antibodies were negative. Electron microscopy (EM) revealed fibrillary deposits in the GBM, confirming the diagnosis of FGN. Review of the literature revealed very few reported similar cases. It appears that severe hypertension and heavy proteinuria, while uncommon in anti-GBM disease, are consistent findings in RPGN form of FGN.
10.5414/CN108508
pubmed_58_15137
Dinosaurs diversified in two steps during the Triassic. They originated about 245 Ma, during the recovery from the Permian-Triassic mass extinction, and then remained insignificant until they exploded in diversity and ecological importance during the Late Triassic. Hitherto, this Late Triassic explosion was poorly constrained and poorly dated. Here we provide evidence that it followed the Carnian Pluvial Episode (CPE), dated to 234-232 Ma, a time when climates switched from arid to humid and back to arid again. Our evidence comes from a combined analysis of skeletal evidence and footprint occurrences, and especially from the exquisitely dated ichnofaunas of the Italian Dolomites. These provide evidence of tetrapod faunal compositions through the Carnian and Norian, and show that dinosaur footprints appear exactly at the time of the CPE. We argue then that dinosaurs diversified explosively in the mid Carnian, at a time of major climate and floral change and the extinction of key herbivores, which the dinosaurs opportunistically replaced.
10.1038/s41467-018-03996-1
pubmed_481_20230
Attention deficit, hyperactivity disorder was recently described in adults. The clinical individualization of this syndrome progressed but the categorical approach remains to be entirely completed. The residual form of the childhood disorder does not generate diagnostic problem when childhood previous history is known. ADHD without childhood history refer us to retrospective difficulties of diagnosis and various evolutions of the infantile form linked or not, with other psychiatric pathologies. Etiology remains unknown, hypothesis of an hereditary disfunction of neurotransmitters is the more studied. These patients can benefit from a psychostimulant treatment. Four controlled studies with methylphenidate demonstrated to be significantly superior to placebo. Even if there are methodological difficulties not resolved (comorbidity, homogeneous population) results are encouraging.
pubmed_481_20230
pubmed_768_5649
PURPOSE To evaluate if the detection rate (DR) of (18)F-choline (18F-CH) PET/CT is influenced by androgen-deprivation therapy (ADT) in patients with prostate cancer (PC) already treated with radical intent and presenting biochemical relapse. MATERIALS AND METHODS We have retrospectively evaluated (18)F-CH PET/CT scans of 325 consecutive PC patients enrolled in the period November 2009 to December 2012 previously treated with radical intent and referred to our centre to perform (18)F-CH PET/CT for biochemical relapse. Two different groups of patients were evaluated. group A included the whole sample of 325 patients (mean age 70 years, range: 49-86) who presented trigger PSA between 0.1 and 80 ng/ml (mean 5.5 ng/ml), and group B included 187 patients (mean age 70 years, range 49-86) with medium-low levels of trigger PSA ranging between 0.5 and 5 ng/ml (mean PSA 2.1 ng/ml); group B was chosen in order to obtain a more homogeneous group of patients in terms of PSA values also excluding both very low and very high PSA levels avoiding the "a priori" higher probability of negative or positive PET scan, respectively. At the time of examination, 139 patients from group A and 72 patients from group B were under ADT: these patients were considered to be hormone-resistant PC patients because from their oncologic history (>18 months) an increase of PSA levels emerged despite the ongoing ADT. The relationship between (18)F-CH PET/CT findings and possible clinical predictors was investigated using both univariate and multivariate binary logistic regression analyses, including trigger PSA and ADT. RESULTS Considering the whole population, overall DR of (18)F-CH PET was 58.2 % (189/325 patients). In the whole sample of patients (group A), both at the univariate and multivariate logistic regression analysis, trigger PSA and ADT were significantly correlated with the DR of (18)F-CH PET (p < 0.05). Moreover, the DR in patients under ADT (mean PSA 7.8 ng/ml) was higher than in patients not under ADT (mean PSA 3.9 ng/ml), (DR was 70.5 % and 48.9 %, respectively; p < 0.001), therefore, demonstrating the existence of a significant correlation between the DR of (18)F-CH PET and ADT. In group B patients only trigger PSA resulted a reliable predictor of the (18)F-CH positivity, since ADT was not correlated to the DR of (18)F-CH PET (p = 0.061). Also in group B the DR of (18)F-CH PET in patients under ADT was higher than in patients not under ADT (65.3 % and 51.3 %, respectively) but the difference was not significant without a statistically significant correlation in the Mann Whitney test (p = 0.456) therefore, suggesting the lack of correlation between DR (18)F-CH PET/CT and ADT. CONCLUSION Similarly to previous published studies, in our series the overall DR of (18)F-CH PET/CT was 58 % and was significantly correlated to trigger PSA. The most important finding of the present study is that ADT does not negatively influence DR of (18)F-CH PET/CT in PC patients with biochemical relapse; therefore, it can be suggested that it is not necessary to withdraw ADT before performing (18)F-CH PET/CT.
10.1007/s00259-014-2720-z
pubmed_626_12812
We present a simple, flexible, and environmentally friendly approach to modify the PDMS surface by gradient-induced migration of embedded amphiphilic copolymer Pluronic F127 and the hydrophobic interaction between the migrated embedded Pluronic and substrate molecules near the surface. The modified surface is hydrophilic and reduces the nonspecific adsorption of protein significantly.
10.1039/b901651a
pubmed_777_5297
Congenital urethral diverticula are a rare finding in adult males. Most cases are diagnosed in childhood or adolescence because of voiding symptoms such as urinary dribbling. Diagnostic workup should include radiography and urethroscopy. The standard therapeutic approach is open surgical excision or endoscopic marsupialization. An unusual case of male congenital urethral diverticula that remained asymptomatic until age 57 is presented.
10.1159/000144069
pubmed_43_13318
PROteolysis-TArgeting Chimeras (PROTACs) is an emerging and promising approach to target intracellular proteins for ubiquitination-mediated degradation, including those so-called undruggable protein targets, such as transcriptional factors and scaffold proteins. To date, plenty of PROTACs have been developed to degrade various disease-relevant proteins, such as estrogen receptor (ER), androgen receptor (AR), RTK, and CDKs. However, the on-target off-tissue and off-target effect is one of the major limitation that prevents the usage of PROTACs in clinic. To this end, we and several other groups have recently developed light-controllable PROTACs, as the representative for the third generation controllable PROTACs, by using either photo-caging or photo-switch approaches. In this review, we summarize the emerging light-controllable PROTACs and the prospective for other potential ways to achieve temporospatial control of PROTACs.
10.3389/fcell.2021.678077
pubmed_14_15338
The new electrochemical thick film biosensors from Roche Diagnostics are presented. Following considerations about the principal requirements that biosensors have to fulfil to be useful for diagnostic purposes, the basic design of these thick film biosensors is shown. In this paper, the new generation of biosensors for glucose, lactate and urea are presented, as well as data from a new biosensor for creatinine. All biosensors are designed for multiple use, at minimum 500 samples or 1 week in-use (depending on type of enzyme used), for determinations in undiluted whole blood or plasma, with extra electrodes to compensate for interferences. The sensors are integrated in a disposable cassette requiring 38 microtl sample volume. The analytical ranges of the sensors scope well with the normal and pathological concentrations of metabolites in human blood, e.g. for glucose 0.5-40.0 mmol/L. Both biosensors and interference-compensating electrodes are developed to have a cycle time of 90 s maximum. Method comparison diagrams show excellent correlation of results obtained by biosensors compared to results achieved by reference methods. In addition, the possibility of urea and creatinine determinations in diluted urine is presented.
10.1007/s00216-001-1186-6
pubmed_808_16626
Nowadays drug-induced hepatotoxicity is urgent problem worldwide. Currently more than 1000 drugs are hepatotoxic and most often are the reason of acute fulminant hepatitis and hepatocellular failure, the states requiring liver transplantation. The paracetamol induced liver toxicity is related with accumulation of its toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI), which is the free radical and enhances peroxidation of lipids, disturbs the energy status and causes death of hepatocytes. During our research we investigated and assessed the efficacy of acetylcysteine, corvitin and their combination in rat model of paracetamol induced acute toxic hepatitis. The study was performed on mature white male Wistar rates with body mass 150-180 g. 50 rats were randomly divided into 5 groups (10 rats in each group). To get the model of acute toxic hepatitis single intraperitoneal injection of paracetamol solution was used (750 mg/kg). Toxic hepatitis was treated with intrapertoneal administration of 40mg/kg acetylcysteine or 100mg/kg corvitin, as well as with combination of these drugs. Monotherapy with acetylcysteine and corvitin of paracetamol induced toxic hepatitis improved the liver function, decreased relative mass of the liver and animal mortality. The treatment of toxic hepatitis was most effective in the case of simultaneous administration of acetylcysteine and corvitin. The normal value of laboratory tests (ALT, ACT, alkaline phosphatase, total and unconjugated bilirubin) was reached and mortality was not more observed. On the bases of obtained data was concluded that acetylcysteine and corvitin have almost equal hepatoprotective activity. The combination of two drugs actually improves the liver function. The most pronounced hepatoprotective effect may be due to synergic action of acetylcysteine and corvitin and such regime can be recommended for correction of liver function.
pubmed_808_16626
pubmed_815_891
pH-Zone-refining counter-current chromatography was applied to the separation of basic amino acid benzyl esters. The method uses a retainer base in the stationary phase to retain analytes in the column and an eluent acid to elute the analytes in the decreasing order of pKa and hydrophilicity. The preparative capability of the method is demonstrated in the separation of a 10-g quantity of the sample.
10.1016/0021-9673(94)80470-2
pubmed_1054_9881
The nonlinear cable equation was solved numerically by means of an implicit procedure. The correlation between end-plate length and fiber diameter was determined in frog (Rana pipiens) sartorius muscles stained with gold chloride (Löwit, 1875). The diameter of the fibers stained by the Löwit method was 80 (74-85) micron (median and its 95% confidence interval for 52 fibers), the length of the end plates in the same fibers was 382 (353-417) micron. The fibers simulated were 80 micron in diameter. To solve the equation the muscle fibers were represented by 500 segments 20 micron long, and the equation was solved in steps of 10 microseconds; a double exponential function was incorporated to the first seven segments to represent the neuromuscular junction. The potential of the first segment of the cable was set to the clamping level and the membrane potential of the remaining segments calculated. The current needed to hold the first segment was estimated by adding the current flowing through the first segment to the current flowing from it to the second segment. Our results indicate that the lack of space clamp in the point voltage-clamp studies of the frog neuromuscular junction introduces serious errors in the estimates of the end-plate conductance value, the kinetics of the conductance changes, and the reversal potential of the end-plate currents. The possibility of an efficient voltage-clamp technique is also explored. Our calculations suggest that the study of end-plate current and conductance is possible with little error if the end-plate potential is controlled at both ends of the synaptic area simultaneously.
10.1016/S0006-3495(82)84505-0
pubmed_398_6368
The loss of myocytes as a consequence of myocardial infarction results in a prompt reduction in regional wall motion and often leads to more protracted and progressive changes in ventricular architecture. The recognition that the process of ventricular enlargement following myocardial infarction is modifiable provided the initial rationale for the use of angiotensin-converting enzyme (ACE) inhibitors as therapy to prevent deterioration in ventricular size and function following infarction. Experimental and clinical studies have documented the effectiveness of this therapy in preventing this late enlargement following infarction. Increasing clinical evidence indicates that this new use of ACE inhibitor therapy in survivors of acute myocardial infarction will lead to an improvement in clinical outcome.
10.1146/annurev.med.46.1.455
pubmed_534_2777
The phase behavior of binary mixtures of γ-oryzanol and β-sitosterol and ternary mixtures of γ-oryzanol and β-sitosterol in sunflower oil was studied. Binary mixtures of γ-oryzanol and β-sitosterol show double-eutectic behavior. Complex phase behavior with two intermediate mixed solid phases was derived from differential scanning calorimetry (DSC) and small-angle X-ray scattering (SAXS) data, in which a compound that consists of γ-oryzanol and β-sitosterol molecules at a specific ratio can be formed. SAXS shows that the organization of γ-oryzanol and β-sitosterol in the mixed phases is different from the structure of tubules in ternary systems. Ternary mixtures including sunflower oil do not show a sudden structural transition from the compound to a tubule, but a gradual transition occurs as γ-oryzanol and β-sitosterol are diluted in edible oil. The same behavior is observed when melting binary mixtures of γ-oryzanol and β-sitosterol at higher temperatures. This indicates the feasibility of having an organogelling agent in dynamic exchange between solid and liquid phase, which is an essential feature of triglyceride networks.
10.1007/s11746-015-2731-3
pubmed_847_5109
BACKGROUND Digital technologies have enabled social connection during prolonged periods of physical distancing and travel restrictions throughout the COVID-19 pandemic. These solutions may exclude older adults, who are at higher risk for social isolation, loneliness, and severe outcomes if infected with SARS-CoV-2. OBJECTIVE This study investigated factors associated with nonuse of social media or video communications to connect with friends and family among older adults during the pandemic's first wave. METHODS A web-based, cross-sectional survey was administered to members of a national retired educators' organization based in Ontario, Canada, between May 6 and 19, 2020. Respondents (N=4879) were asked about their use of social networking websites or apps to communicate with friends and family, their internet connection and smartphone access, loneliness, and sociodemographic characteristics. Factors associated with nonuse were evaluated using multivariable logistic regression. A thematic analysis was performed on open-ended survey responses that described experiences with technology and virtual connection. RESULTS Overall, 15.4% (751/4868) of respondents did not use social networking websites or apps. After adjustment, male gender (odds ratio [OR] 1.60, 95% CI 1.33-1.92), advanced age (OR 1.88, 95% CI 1.38-2.55), living alone (OR 1.68, 95% CI 1.39-2.02), poorer health (OR 1.33, 95% CI 1.04-1.71), and lower social support (OR 1.44, 95% CI 1.20-1.71) increased the odds of nonuse. The reliability of internet connection and access to a smartphone also predicted nonuse. Many respondents viewed these technologies as beneficial, especially for maintaining pre-COVID-19 social contacts and routines, despite preferences for in-person connection. CONCLUSIONS Several factors including advanced age, living alone, and low social support increased the odds of nonuse of social media in older adults to communicate with friends and family during COVID-19's first wave. Our findings identified socially vulnerable subgroups who may benefit from intervention (eg, improved access, digital literacy, and telephone outreach) to improve social connection.
10.2196/34793
pubmed_902_6123
The in vitro activities of ceftaroline, a novel, parenteral, broad-spectrum cephalosporin, and four comparator antimicrobials were determined against anaerobic bacteria. Against Gram-positive strains, the activity of ceftaroline was similar to that of amoxicillin-clavulanate and four to eight times greater than that of ceftriaxone. Against Gram-negative organisms, ceftaroline showed good activity against beta-lactamase-negative strains but not against the members of the Bacteroides fragilis group. Ceftaroline showed potent activity against a broad spectrum of anaerobes encountered in respiratory, skin, and soft tissue infections.
10.1128/AAC.01788-09
pubmed_157_21654
CONTEXT Acne vulgaris affects about 85% of teenagers and may continue to adulthood. There are about two million visits to physicians per year for teenagers and the direct cost of acne treatment in the US exceeds $1 billion per year. EVIDENCE ACQUISITION A wide variety of treatment regimens exist for acne vulgaris including benzoil peroxide, retinoids, isotretinoids, keratolytic soaps, alpha hydroxy acids, azelaic acid, salicilic acid as well as hormonal, anti-androgen or antiseborrheic treatments. However, none of these methods is free of side effects and their exact role in therapy is not clear. In this paper apart from presenting the possible causes of acne vulgaris and its available drugs, recently published papers about medicinal plants used in the treatment of acne vulgaris were reviewed. RESULTS Consumption of alternative and complementary medicine, including medicinal plants, is increasing and is common amongst patients affected by acne and infectious skin diseases. Medicinal plants have a long history of use and have been shown to possess low side effects. These plants are a reliable source for preparation of new drugs. CONCLUSIONS Many plants seem to have inhibitory effects on the growth of bacteria, fungi and viruses in vitro. However, there are a few clinical evidences about the effectiveness and safety of these plants in the treatment of acne and other skin infections.
10.5812/jjm.25580
pubmed_786_2875
Highly reactive transition metals, such as copper and iron play an obligatory role in generating of reactive oxygen species (ROS). Many neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD) show increased accumulation of these metals. Phosphoinositide metabolism is altered in neurodegenerative diseases. In the present study, we examined the effect of CuSO(4) and FeCl(2) on phospholipase C (PLC) activity degrading phosphatidylinositol-4,5-bisphosphate (PIP(2)) and phosphatidylinositol (PI) in synaptic plasma membranes (SPM) from the rat brain cortex. We report that 25 microM CuSO(4) and FeCl(2) decreased PIP(2)-PLC activity by 60% and 75%, respectively. However, both compounds had no effect on PI-PLC activity. These data indicated that exclusively PIP(2)-PLC is sensitive to transition metal ions. We suggest that chelators of these metals may protect brain against alteration of phosphoinositide metabolism and might be beneficial in the treatment of neurodegenerative diseases.
pubmed_786_2875
pubmed_120_12401
Human cytomegalovirus (HCMV) has developed multiple strategies to escape immune recognition. Here, we demonstrate that HCMV down-regulates HLA-DR expression in infected interferon gamma (IFN-gamma)-stimulated fibroblasts at 1 day after infection. Decreased HLA-DR expression was not observed on cells infected with an HCMV strain lacking the pp65 gene (RVAD65), but was observed on cells transfected with the pp65 gene. HLA-DR expression accumulated in vacuoles near the nucleus in HCMV-infected, but not in uninfected or RVAD65-infected cells. In addition, the HLA-DR alpha-chain, but not the beta-chain or HLA-DM, was degraded in HCMV-infected but not in RVAD65-infected cells. Thus, the HCMV protein pp65 mediates decreased expression of HLA-DR, by mediating an accumulation of HLA class II molecules in lysosomes that results in degradation of the HLA-DR alpha-chain.
10.1182/blood-2002-05-1504
pubmed_30_4825
A device for manual compression and palpation during supine fluoroscopy has been designed. It enables effective use of the physiologic grasping and lever force potentials of the hand and wrist. The device permits optimal fluoroscopic palpation and compression techniques and prevents direct exposure to the lead-gloved hand.
10.1148/radiology.170.2.2911686
pubmed_203_245
Nematode mitochondria expresses two types of extremely truncated tRNAs that are specifically recognized by two distinct elongation factor Tu (EF-Tu) species named EF-Tu1 and EF-Tu2. This is unlike the canonical EF-Tu molecule that participates in the standard protein biosynthesis systems, which basically recognizes all elongator tRNAs. EF-Tu2 specifically recognizes Ser-tRNA(Ser) that lacks a D arm but has a short T arm. Our previous study led us to speculate the lack of the D arm may be essential for the tRNA recognition of EF-Tu2. However, here, we showed that the EF-Tu2 can bind to D arm-bearing Ser-tRNAs, in which the D-T arm interaction was weakened by the mutations. The ethylnitrosourea-modification interference assay showed that EF-Tu2 is unique, in that it interacts with the phosphate groups on the T stem on the side that is opposite to where canonical EF-Tu binds. The hydrolysis protection assay using several EF-Tu2 mutants then strongly suggests that seven C-terminal amino acid residues of EF-Tu2 are essential for its aminoacyl-tRNA-binding activity. Our results indicate that the formation of the nematode mitochondrial (mt) EF-Tu2/GTP/aminoacyl-tRNA ternary complex is probably supported by a unique interaction between the C-terminal extension of EF-Tu2 and the tRNA.
10.1093/nar/gki784