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pubmed_977_7432
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This phase I study was designed to: (1) determine the maximum tolerated dose (MTD) and recommended dose (RD) of the fibroblast growth factor receptor (FGFR) inhibitor futibatinib in Japanese patients with advanced solid tumors, and (2) examine the antitumor activity of the RD in patients with gastric cancer (GC) or other advanced solid tumors who have FGFR or FGF/FGFR abnormalities, respectively. In the dose-escalation phase, patients were assigned to 21-day cycles of oral futibatinib 8-160 mg three times a week (TIW) or 16 or 20 mg once daily (QD). In the expansion phase, patients received oral futibatinib 56, 80, or 120 mg TIW, or 16 or 20 mg QD. Eighty-three patients received futibatinib TIW (n = 40) or QD (n = 43). No dose-limiting toxicities were observed according to the final study protocol definition, and the MTD was not reached. The most common adverse events with both regimens were hyperphosphatemia (TIW, 82.5%; QD, 100.0%) and decreased appetite (TIW, 40.0%; QD, 58.1%). Hyperphosphatemia was asymptomatic, not leading to futibatinib discontinuation. The overall response rate (ORR) was 11.5% in patients with FGF/FGFR abnormalities. Notably, in GC patients harboring FGFR2 copy number (CN) ≥10, the ORR was 36.4% versus 0 in patients with CN <10. Therefore, futibatinib had a generally predictable and manageable safety profile in patients with advanced solid tumors. Antitumor activity was seen in patients with FGF/FGFR abnormalities, particularly those with GC and high FGFR2 CNs. Thus, futibatinib 20 mg QD was chosen as the RD for phase II studies.
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10.1111/cas.15486
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pubmed_969_6960
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In order to establish the mechanism of perturbation of hormonally regulated calcium homeostasis in hepatocytes caused by menadione, the effects of menadione on hepatic alpha 1-adrenergic receptors and on alpha 1-adrenergic receptor-mediated increase in cytosolic free calcium concentration were determined. Menadione had no detectable effect on the alpha 1-adrenergic receptor but significantly inhibited (-)-epinephrine-dependent increases in intracellular free calcium concentration in Quin2 acetoxymethyl ester-loaded hepatocytes. The hormonally induced increase in intracellular free calcium concentration is caused by formation of inositol 1,4,5-trisphosphate (IP3) which binds to a specific receptor and causes a release of intracellular ATP-dependently sequestrated calcium. The IP3-stimulated release of calcium from intracellular pools in hepatocytes was inhibited to a great extent after treatment with menadione. This inhibition could also be observed after treatment of hepatocytes with p-benzoquinone and N-ethylmaleimide and could not be reversed by the thiol-reducing reagent dithiothreitol which indicated covalent binding to an essential free sulfhydryl group. The inhibition of IP3-dependent release of intracellular calcium was accompanied by a large increase in the number of detectable IP3 receptors without any change in the dissociation constant as determined in permeabilized hepatocytes. The increase in IP3 receptors caused by menadione could be reversed by dithiothreitol which suggests the involvement of free sulfhydryl groups. It is concluded that the IP3 receptor plays an important role in the mechanism of menadione-induced perturbation of hormonally regulated calcium homeostasis in rat hepatocytes.
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10.1016/0006-2952(91)90598-y
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pubmed_112_12877
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Fractures of the proximal fifth metatarsal can be divided into two distinct groups based on anatomical location and clinical course. Fractures of the tuberosity often heal well with nonoperative treatment, whereas fractures occurring in the proximal diaphysis (up to 1.5 cm distal to the tuberosity) have significantly increased risk for delayed union or nonunion. It is the purpose of this paper to describe the intraosseous vascular anatomy of the fifth metatarsal, and the clinical implications for basilar fracture healing. Ten fresh-frozen amputation or cadaver specimens were studied following arterial injection with India ink or barium sulfate suspension. The intraosseous blood supply to the fifth metatarsal tuberosity arose from numerous metaphyseal vessels penetrating the nonarticular surfaces of the tuberosity in a random, radiate pattern. The blood supply to the proximal diaphysis was derived primarily from the nutrient artery, which gave rise to longitudinal intramedullary branches. The arterial supply to the tuberosity joined the supply of the proximal diaphysis in the area just distal to the tuberosity, corresponding to the region of poor prognosis for fracture healing. This suggests that a relative lack of blood supply following a proximal diaphyseal fracture may contribute to delayed union and nonunion.
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10.1177/107110079201300306
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pubmed_739_21985
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Clear seismic-related anomalies in the radon (222Rn) concentration of the atmosphere were observed prior to the Kobe earthquake (magnitude 7.2) on 17 January 1995. The radon anomalies were observed at a monitoring station in Kobe, which is located about 20 km away from the epicenter. The means of radon concentration in the atmosphere for each day were calculated using the data observed between April 1984 and March 1994, in order to obtain the normal radon variation. The difference between the smoothed radon concentration and the smoothed mean radon concentration is the residual value. Using the weekly averages of residual values in the historical period, the weekly residual value in the validation period were predicted. The historical period was from April 1984 to March 1994. The validation period was from April 1994 to January 1996. The seismic-related radon anomaly higher than the 99% confidence limit of the residual value of radon concentration in the atmosphere was observed beginning about 2 mo before the earthquake.
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10.1097/00004032-199705000-00012
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pubmed_721_5340
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A laser Raman study has been made on the conformation of a series of self-complementary octameric deoxynucleotides that contain all four canonical deoxynucleotide bases [guanine (G), cytosine (C), adenine (A), and thymine (T)] in order to determine which sequences will crystallize in the Z form and which sequences will go into the Z form in aqueous solution at high salt concentrations (4-6 M NaCl). All four octadeoxynucleotides, d(TGCGCGCA) (I), d(CACGCGTG) (II), d(CGTGCACG) (III), and d(CGCATGCG) (IV), have been crystallized from low-salt solutions. The Raman spectra of microcrystals show that I, II, and IV crystallize in a rigorous Z form while III crystallizes in the B form. Sequences I and II go into a Z form in 4-6 M NaCl solution at 0 degrees C while sequences III and IV remain in the B form in 6 M salt. There are substantial differences in the Raman spectra of oligonucleotides in the Z form found in the crystal and in high-salt solutions. The Raman spectra of the Z forms in 6 M NaCl solution at 0 degrees C are not linear combinations of the Raman spectra of the complete Z form in the crystal and the complete B form in low-salt solutions. The terminal residues of these oligomers do not appear to be in a strict Z form. A detailed analysis of the ring puckers and syn/anti conformation for all of the residues both in solution and in the crystal has been made.(ABSTRACT TRUNCATED AT 250 WORDS)
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10.1021/bi00390a042
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pubmed_584_5970
|
The effects of aging on blood oxygen level dependent signal changes and the hemodynamic response (HDR) remain controversial. Using functional magnetic resonance (MR) imaging, we examined the HDR properties and activated voxel counts in striate and extrastriate cortex in 18 healthy elderly subjects in response to a simple visual paradigm. Subjects of equal number and gender were prospectively separated into groups from the seventh, eighth, and ninth decades. Activation data were compared with those of 6 healthy subjects aged 30-39 under the same conditions. We found no systematic difference in HDR amplitude, shape, or latency across these groups. However, increasing age over 60 was associated with a significant decline in activated voxel counts, relative to the young controls. The results are discussed in comparison with previously published studies and in the context of the effects of aging on MR signal change. While robust activation can be produced in the striate and extrastriate cortices until the end of the ninth decade, caution should be exercised when comparing data from subjects in different decades. As functional magnetic resonance imaging is increasingly being used to examine patients with stroke and dementia, these results emphasize the importance of careful selection and age matching of control subjects when comparing with a patient population affected by disease processes associated with aging.
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10.1016/s1053-8119(03)00237-4
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pubmed_887_11383
|
Development is the ordered sequence of changes in plant form and phenology that occurs through time. As such it is distinguished from that of growth and includes the succession of ontogenetic stages as well as the initiation of leaves, shoots and roots. It is more useful to look at rates of development as functions of environmental influences rather than, for example, total number of days to a given stage. It is often found that linear, or close to linear, relationships are found between rates and temperature, photoperiod and the duration of cold temperatures. These ideas are treated theoretically and illustrated with data from an experiment where wheat was grown at ten sites in Britain. We conclude that temperature is the most important factor governing differences in developmental rates between sites and sowing dates, especially for later stages of development. Variation in the timing of earlier stages depends on either exposure to photoperiods of different lengths or on the degree of vernalization of the plants. Calculation is made of the maximum effectiveness of these environmental factors in shortening the vegetative phases in a range of wheat cultivars and the basis of their interaction is also explored. For wheat it seems that they act multiplicatively in their effect on developmental rate. The rate at which plants produce their leaves is important in canopy development. The sensitivity of the rate of leaf emergence, measured in thermal time, has been linked to the rate at which daylength changes (d phi/dt). A possible mechanism may involve plants responding to the ratio of light in the red (R, ca 660 nm) and far-red (FR, ca 730 nm) wavebands (R/FR). This ratio decreases when d phi/dt is becoming more negative and vice versa. Linkage can be found between the change in R/FR at twilight and commensurate changes in calculated phytochrome photoequilibria. Thus, the possibility exists that phytochrome may be involved in modulating the leaf production rate in response to different sowing dates. Alternatively, variation in rate of leaf production may be through changes in the base temperature, in response to the 'spectrum' of temperatures the plants experience during development. Thus, any involvement of photoperiod in this response may be spurious. Controlled environment studies of leaf emergence tend to support this latter interpretation as does analysis of experiments from three European sites.
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pubmed_887_11383
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pubmed_269_25533
|
Since the beginning of the COVID-19 pandemic, the wastewater-based epidemiology (WBE) of SARS-CoV-2 has been used as a complementary indicator to follow up on the trends in the COVID-19 spread in Belgium and in many other countries. To further develop the use of WBE, a multiplex digital polymerase chain reaction (dPCR) assay was optimized, validated and applied for the measurement of emerging SARS-CoV-2 variants of concern (VOC) in influent wastewater (IWW) samples. Key mutations were targeted in the different VOC strains, including SΔ69/70 deletion, N501Y, SΔ241 and SΔ157. The presented bioanalytical method was able to distinguish between SARS-CoV-2 RNA originating from the wild-type and B.1.1.7, B.1.351 and B.1.617.2 variants. The dPCR assay proved to be sensitive enough to detect low concentrations of SARS-CoV-2 RNA in IWW since the limit of detection of the different targets ranged between 0.3 and 2.9 copies/µL. This developed WBE approach was applied to IWW samples originating from different Belgian locations and was able to monitor spatio-temporal changes in the presence of targeted VOC strains in the investigated communities. The present dPCR assay developments were realized to bring added-value to the current national WBE of COVID-19 by also having the spatio-temporal proportions of the VoC in presence in the wastewaters.
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10.3390/v14030610
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pubmed_906_1863
|
In the present study, we have shown that exposure of insulin-secreting clonal beta (HIT-T15) cells to interleukin-1beta (IL-1beta) results in a time- and concentration-dependent increase in nitric oxide (NO) release. These effects by IL-1beta on NO release were mediated by induction of inducible nitric oxide synthase (iNOS) from the cells. Preincubation of HIT cells with Clostridium sordellii lethal toxin-82, which irreversibly glucosylates and inactivates small G-proteins, such as Ras, Rap, Ral, and Rac, but not Cdc42, completely abolished IL-1beta-induced NO release. Pre-exposure of HIT cells to C. sordellii lethal toxin-9048, which monoglucosylates and inhibits Ras, Cdc42, Rac, and Rap, but not Ral, also attenuated IL-1beta-mediated NO release. These data indicate that activation of Ras and/or Rac may be necessary for IL-1beta-mediated NO release. Preincubation of HIT cells with C. difficile toxin-B, which monoglucosylates Rac, Cdc42, and Rho, had no demonstrable effects on IL-mediated NO release, ruling out the possibility that Rac may be involved in this signaling step. Further, two structurally dissimilar inhibitors of Ras function, namely manumycin A and damnacanthal, inhibited, in a concentration-dependent manner, the IL-1beta-mediated NO release from these cells. Together, our data provide evidence, for the first time, that Ras activation is an obligatory step in IL-1beta-mediated NO release and, presumably, the subsequent dysfunction of the pancreatic beta cell. Our data also provide a basis for future investigations to understand the mechanism of cytokine-induced beta cell death leading to the onset of insulin-dependent diabetes mellitus.
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10.1016/s0006-2952(01)00818-8
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pubmed_450_6733
|
We report the first systematic evolution and study of tRNA variants that are able to read a set of UAGN (N = A, G, U, C) codons in a genomically recoded E. coli strain that lacks any endogenous in-frame UAGN sequences and release factor 1. Through randomizing bases in anticodon stem-loop followed by a functional selection, we identified tRNA mutants with significantly improved UAGN decoding efficiency, which will augment the current efforts on genetic code expansion through quadruplet decoding. We found that an extended anticodon loop with an extra nucleotide was required for a detectable efficiency in UAGN decoding. We also observed that this crucial extra nucleotide was converged to a U (position 33.5) in all of the top tRNA hits no matter which UAGN codon they suppress. The insertion of U33.5 in the anticodon loop likely causes tRNA distortion and affects anticodon-codon interaction, which induces +1 frameshift in the P site of ribosome. A new model was proposed to explain the observed features of UAGN decoding. Overall, our findings elevate our understanding of the +1 frameshift mechanism and provide a useful guidance for further efforts on the genetic code expansion using a non-canonical quadruplet reading frame.
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10.1038/srep21898
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pubmed_74_7305
|
BACKGROUND
Duloxetine is an antidepressant that is also useful in chronic neuropathic and central origin pain. In this study, the role of duloxetine in decreasing acute postoperative pain after lumbar canal stenosis surgery is explored.
METHODS
In this single center, triple blinded, and placebo-controlled trial, 96 patients were randomized for statistical analysis. The intervention group received oral duloxetine 30 mg once a day (OD) for 2 days before surgery, 60 mg OD from the day of surgery to the postoperative second day and 30 mg OD for the next 2 days (a total duration of 7 days). A placebo capsule was given in the other group for a similar time and schedule. The same standard perioperative analgesia protocols were followed in both groups.
RESULTS
Total morphine consumption up to 24 hours was significantly decreased in the duloxetine group (P < 0.01). The time to the first analgesia requirement was similar in both groups but the time to the second and third dose of rescue analgesia increased significantly in the duloxetine group. The time to ambulation was decreased significantly (P < 0.01) in the duloxetine group as compared to the placebo group. Pain scores remained similar during most of the time interval. No significant difference was observed in the complication rate and patient satisfaction score recorded.
CONCLUSIONS
Duloxetine reduces postoperative pain after lumbar canal stenosis surgery with no increase in adverse effects.
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10.3344/kjp.2020.33.1.40
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pubmed_1041_5346
|
We present a novel application of active voltage control of DNA captured in a nanopore to regulate the amount of time the DNA is available to molecules in the bulk phase that bind to the DNA. In this work, the control method is used to measure hybridization between a single molecule of DNA captured in a nanopore and complementary oligonucleotides in the bulk phase. We examine the effect of oligonucleotide length on hybridization, and the effect of DNA length heterogeneity on the measurements. Using a mathematical model, we are able to deduce the binding rate of complementary oligonucleotides, even when DNA samples in experiments are affected by heterogeneity in length. We analyze the lifetime distribution of DNA duplexes that are formed in the bulk phase and then pulled against the pore by reversing the voltage. The lifetime distribution reveals several dissociation modes. It remains to be resolved whether these dissociation modes are due to DNA heterogeneity or correspond to different states of duplex DNA. The control method is unique in its ability to detect single-molecule complex assembly in the bulk phase, free from external force and with a broad (millisecond-to-second) temporal range.
|
10.1016/j.bpj.2011.01.029
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pubmed_578_11387
|
Borrelia burgdorferi is a causative agent of Lyme disease in North America and Eurasia. The first complete genome sequence of B. burgdorferi strain 31, available for more than a decade, has assisted research on the pathogenesis of Lyme disease. Because a single genome sequence is not sufficient to understand the relationship between genotypic and geographic variation and disease phenotype, we determined the whole-genome sequences of 13 additional B. burgdorferi isolates that span the range of natural variation. These sequences should allow improved understanding of pathogenesis and provide a foundation for novel detection, diagnosis, and prevention strategies.
|
10.1128/JB.01158-10
|
pubmed_1055_14298
|
BACKGROUND
Uninsured patients have poor access to screening colonoscopy and subsequently present with advanced stages of colorectal cancer (CRC) that beget worse outcomes and higher total costs. Providing pro bono colonoscopies to uninsured patients at high risk for CRC can detect early stage disease and be cost-effective.
STUDY DESIGN
Patients considered at increased risk for CRC were offered free screening colonoscopies. Patient data from these colonoscopies were collected during a 12-month period, and the incidence of CRC was compared with a control group of uninsured patients from the Surveillance, Epidemiology, and End Results (SEER) registry. Published estimates derived from SEER Medicare data of health expenditures by CRC stage were used to develop a cost model. To compare overall costs between our cohort and the SEER control, the mean initial cost of care (up to 1 year) was weighted by the stage-specific CRC incidence in each group.
RESULTS
There were 682 uninsured patients screened, with 9 cancers identified (stage 0, n = 1; stage I, n = 3; stage II, n = 2; and stage III, n = 3) for an incidence of 1.3%. A total cost of $388,137 was estimated to be incurred during the initial phase of care. Compared with the SEER control, our cohort included more early stage cancers and subsequently had a marginally lower per-patient initial cost ($43,126 vs $43,736).
CONCLUSIONS
Our screening criteria successfully identified a high-risk population with an overall 1.3% incidence of CRC. For these patients, the provision of free screening colonoscopies identified earlier-stage tumors and appears to be cost-neutral.
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pubmed_1055_14298
|
pubmed_968_772
|
INTRODUCTION
Total femoral replacement (TFR), it is an uncommon surgery in non-oncological patients. Our main objective is to review our total femur replacement surgeries and analyze functional and clinical outcomes.
MATERIAL AND METHODS
We retrospectively review our series of seven non-oncological patients treated at our center with a TFR from 2011 to 2014. After excluding patients (Oncological patients or non-follow up) we revised four patients. Paprosky bone loos classification and different values were studied: number and time of surgeries, complications, revision surgeries, functional scales, and follow-up.
RESULTS
Mean age of 78.5 years. According to Paprosky classification of femur bone loss: 1 IIIA, 2 were IIIB, 1 IV. On the other side acetabular loss: 2 I, 1 IIA, 1 IIB. Surgical time for TFR was 110 minutes on average. Three patients were need revision surgery due to instability. And every single patient suffered from chronic infection. Mean range of motion was 85 flexion, 0o extension. Comparing preoperative and postoperative Harris Hip Score for hip function was 54.9 points and Enneking score was an average of 14.25 points better in our patients with TFR. Visual analogue pain score was on average less than two points. Mean follow-up is almost seven and a half years.
CONCLUSIONS
TFP has not a standardized surgical protocol yet. Infection is always present in our series and acetabular constrained components in TFR avoid instability complications. TFP should be implanted only in selected patients.
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pubmed_968_772
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pubmed_932_4432
|
OBJECTIVE
To test whether changes in the patient activation measure (PAM) are related to changes in health status and healthy behaviors.
METHODS
Data for this secondary analysis were taken from a group-randomized, controlled trial comparing a traditional health promotion program for employees with an activated consumer program and a control program. The study population included 320 employees (with and without chronic disease) from two U.S. companies: a large, integrated health care system and a national airline. Survey and biometric data were collected in Spring 2005 (baseline) and Spring 2007 (follow-up).
RESULTS
Change in PAM was associated with changes in health behaviors at every level (1-4), especially at level 4. Changes related to overall risk score and many of its components: aerobic exercise, safety, cancer risk, stress and mental health. Other changes included frequency of eating breakfast and the likelihood of knowing about health plans and how they compare.
CONCLUSION
Level 4 of patient activation is not an end-point. People are capable of continuing to make significant change within this level.
PRACTICE IMPLICATIONS
Interventions should be designed to encourage movement from lower to higher levels of activation. Even people at the most activated level improve health behaviors.
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10.1016/j.pec.2012.02.005
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pubmed_100_17499
|
Adult-born neurons are continuously generated and incorporated into the circuitry of the hippocampus throughout life in mammals. Cumulative evidence supports a physiological role for adult-born neurons, yet it not clear whether this subset of dentate granule cells makes a unique contribution to hippocampal function. Perturbation or ablation of adult hippocampal neurogenesis leads to deficits in the acquisition of learned associations or memory recall, whereas an increase in adult hippocampal neurogenesis enhances some forms of learning and memory. The observed effects thus far appear to be task-dependent, species-specific, and sensitive to the timing of manipulations. Here, we review the recent evidence correlating adult-born dentate granule cells (DGCs) with hippocampal-dependent behavior and focus on the dynamic properties of this neuronal population that may underlie its function. We further discuss a framework for future investigations of how newly integrated neurons may contribute to hippocampal processing using advanced genetic techniques with enhanced temporal resolution.
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10.1016/j.bbr.2011.07.012
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pubmed_345_20127
|
The generation of random numbers is a task of paramount importance in modern science. A central problem for both classical and quantum randomness generation is to estimate the entropy of the data generated by a given device. Here we present a protocol for self-testing quantum random number generation, in which the user can monitor the entropy in real time. Based on a few general assumptions, our protocol guarantees continuous generation of high quality randomness, without the need for a detailed characterization of the devices. Using a fully optical setup, we implement our protocol and illustrate its self-testing capacity. Our work thus provides a practical approach to quantum randomness generation in a scenario of trusted but error-prone devices.
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10.1103/PhysRevLett.114.150501
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pubmed_933_17954
|
BACKGROUND
With the growing use of pharmacokinetic (PK)-driven drug delivery and/or drug advisory displays, identifying the PK model that best characterizes propofol plasma concentration (Cp) across a variety of dosing conditions would be useful. We tested the accuracy of 3 compartmental models and 1 physiologically based recirculatory PK model for propofol to predict the time course of propofol Cp using concentration-time data originated from studies that used different infusion schemes.
METHODS
Three compartmental PK models for propofol, called the "Marsh," the "Schnider," and the "Schüttler" models, and 1 physiologically based recirculatory model called the "Upton" model, were used to simulate the time course of propofol Cp. To test the accuracy of the models, we used published measured plasma concentration data that originated from studies of manual (bolus and short infusion) and computer-controlled (target-controlled infusion [TCI] and long infusion) propofol dosing schemes. Measured/predicted (M/P) propofol Cp plots were constructed for each dataset. Bias and inaccuracy of each model were assessed by median prediction error (MDPE) and median absolute prediction error (MDAPE), respectively.
RESULTS
The M/P propofol Cp in the 4 PK models revealed bias in all 3 compartmental models during the bolus and short infusion regimens. In the long infusion, a worse M/P propofol Cp at higher concentration was seen for the Marsh and the Schüttler models than for the 2 other models. Less biased M/P propofol Cp was found for all models during TCI. In the bolus group, after 1 min, a clear overprediction was seen for all 3 compartmental models for the entire 5 min; however, this initial error resolved after 4 min in the Schnider model. The Upton model did not predict propofol Cp accurately (major overprediction) during the first minute. During the bolus and short infusion, the Marsh model demonstrated worse MDPE and MDAPE compared with the 3 other models. During short infusion, MDAPE for the Schnider and Schüttler models was better than the Upton and the Marsh models. All models showed similar MDPE and MDAPE during TCI simulations. During long infusion, the Marsh and the Schüttler models underestimated the higher plasma concentrations.
CONCLUSION
When combining the performance during various infusion regimens, it seems that the Schnider model, although still not perfect, is the recommended model to be used for TCI and advisory displays.
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10.1213/ANE.0b013e3181bdcf5b
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pubmed_534_2806
|
The scholarship in building community capacity by way of cultivating community social capital and community spirit through neighborhood design has spawned heated debates in urban and community studies. This paper contributes to this scholarship by examining the neighborhood contexts of grassroots participation in Chinese contemporary urban communities. In particular, it explores the relationship between neighborhood communal space and community participation, using a city-wide survey of 1,809 households in 39 commodity housing estates in the city of Guangzhou. It is found that local residents' participation in community affairs is conditioned by both the social milieu (measured by the overall level of social cohesion) and the physical environment (indicated by effects of communal space) of a neighborhood. Notably, communal space exerts positive indirect effects on grassroots participation by facilitating the development of place-based social capital and neighborhood attachment. These findings point to a civic virtue of communal space and provide nascent evidence regarding neighborhood contexts of grassroots participation in urban China.
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10.1016/j.habitatint.2014.10.013
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pubmed_496_11414
|
Five years after publication of the Institute for Medicine's landmark 1999 report,To Err Is Human, notable advances have been made. They include the development of performance standards, an increase in error reporting, integration of information technology, and improved safety systems. But the IOM notes that efforts are still needed to improve safety and reduce errors, including development of data standards for patient safety information, establishment of a national health information infrastructure, and comprehensive patient safety programs in health care organizations.
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pubmed_496_11414
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pubmed_335_25832
|
BACKGROUND
Minimally invasive surgeries are increasingly common as the first option for most urological diseases. However, laparoscopic techniques are difficult to master, especially for surgeons who were not trained during their residency programs. Therefore, postgraduate courses are important for such matters. This study aims to evaluate the results of postgraduate courses in minimally invasive urological surgery.
METHODS
A specific questionnaire was used to evaluate the impact of the course on urologists' professional activities. The questionnaire also evaluated demographic data and previous surgical experience. The postgraduate course was divided into 10 monthly modules, each one with 36 hours of activities, from March to December. All students of the laparoscopic postgraduate course from the last five years were enrolled in the study.
RESULTS
Forty-one students were included in the study. Thirty-nine students were male (95.1%), and the mean age was 39.5 years (range, 30-60 years). Students from all regions of the country were enrolled. Thirty (73.2%) students had minor laparoscopic experience. All students improved their laparoscopic skills and were able to include new procedures in their daily surgical practice. Eleven students (26.8%) had no laparoscopic experience, and all of them started to perform laparoscopic procedures. The median level of impact on professional life was 75 points (range, 0-100 points).
CONCLUSIONS
The postgraduate course is an appropriate way to acquire urological laparoscopic skills. The annual course allowed improvement and initiation of laparoscopic procedures, which significantly impacted urologists' daily activities.
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10.21037/tau.2018.03.18
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pubmed_358_19517
|
We performed a randomised controlled study to assess the accuracy of computer-assisted pedicle screw insertion versus conventional screw placement under clinical conditions. One hundred patients scheduled for posterior thoracolumbar or lumbosacral pedicle screw instrumentation were randomised into two groups, either for conventional pedicle screw placement or computer-assisted screw application using an optoelectronic navigation system. From the computer-assisted group, nine patients were excluded: one because of an inadequate preoperative computed tomography study, seven because of problems with the specific instruments or the computer system, and one because of an intraoperative anesthesiological complication. Thus, there were 50 patients in the conventional group and 41 in the computer-assisted group, and the number of screws inserted was 277 and 219, respectively. There was no statistical difference between the groups concerning age, gender, diagnosis, type of operation performed, mean operating time, blood loss, or number of screws inserted. The time taken for screw insertion was significantly longer in the computer-assisted group. Postoperatively, screw positions were assessed by an independent radiologist using a sophisticated CT imaging protocol. The pedicle perforation rate was 13.4% in the conventional group and 4.6% in the computer-assisted group (P = 0.006). Pedicle perforations of more than 4 mm were found in 1.4% (4/277) of the screw insertions in the conventional group, and none in the computer-assisted group. Complications not related to pedicle screws were two L5 nerve root lesions, one end plate fracture, one major intraoperative bleeding and one postoperative death in the conventional group, and one deep infection in the computer-assisted group. In conclusion, pedicular screws were inserted more accurately with image-guided computer navigation than with conventional methods.
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10.1007/s005860000146
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pubmed_411_15625
|
Studies in recent years have shown that academic procrastination in postgraduates is very common and has a negative impact on their mental health. Therefore, we conducted this study to explore the influencing mechanism of postgraduate academic procrastination. In this study, based on the Temporal Decision Model (TDM) of procrastination and the strength model of self-control, we administered a questionnaire survey to 577 full-time postgraduates (351 females, 226 males) to explore the influence mechanisms and gender differences of motivational and volitional factors on academic procrastination. Our results indicated significant differences in academic self-efficacy between females and males. Academic self-efficacy was positively correlated with academic self-control and negatively correlated with academic procrastination; academic self-control was negatively correlated with academic procrastination. Academic self-control had a completely mediating effect in the influence of academic self-efficacy on academic procrastination. Gender variables moderated the influence of academic self-efficacy on academic self-control and thus significantly moderated the mediating effect of academic self-control. Specifically, academic self-control had a stronger mediating effect between academic self-efficacy and academic procrastination for female postgraduates. Our findings may provide guidance for postgraduates who exhibit academic procrastination and extend the theory of academic procrastination.
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10.3389/fpsyg.2020.01752
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pubmed_559_4107
|
Clearance of hepatitis B surface antigen (HBsAg) by lamivudine is achieved in only a small proportion of patients with chronic hepatitis B virus (HBV) infection. We investigated the effect of lamivudine on de novo HBV reactivation after living-donor liver transplantation when the number of HBV was expected to be very small. Thirty-eight HBV-naive recipients who received liver grafts from antibodies to core antigen-positive donors receiving hepatitis B immunoglobulin (HBIG) were studied. HBsAg appeared in nine cases (23.7 %) despite receiving HBIG for 12-71 months (mean: 35.1 months) after transplantation. Lamivudine treatment was started in six recipients during the acute phase of HBV reactivation. Five of the six recipients achieved complete clearance of HBsAg in sera at a median of 4.6 months (ranging from 21 to 330 days) after lamivudine administration. Although lamivudine was stopped in four cases, all remained negative for HBsAg. Our findings suggested that short-term lamivudine treatment during acute phase of HBV reactivation could achieve complete clearance of HBsAg in a significant number of liver transplant recipients.
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10.1111/j.1600-6143.2006.01542.x
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pubmed_977_21403
|
BACKGROUND
Spinal muscular atrophy (SMA) is a rare degenerative neuromuscular disease, mostly occurring in infants and children, leading to muscle wasting and weakness, and premature death. Due to new developments of multiple disease-modifying treatments within the last years, the interest of research in patients affected by SMA increased steadily. However, the psychosocial situation of parents as informal caregivers is still rarely addressed.
OBJECTIVES
This review aims to highlight quantitative and qualitative data about the psychosocial situation, caregiver burden, and needs of parents as informal caregivers for children and adolescents with SMA.
METHODS
A systematic literature review was performed including quantitative and qualitative original studies focusing on different psychosocial aspects and outcomes for parents of children and adolescents < 21 years of age with SMA type I-IV (PROSPERO; registration number CRD42020219020). We searched the following databases in November 2020 with a research update in August 2021: MEDLINE, CINAHL, PsycINFO and Web of Science.
RESULTS
In total, 24 articles from 23 studies were selected for inclusion (15 quantitative studies, 7 articles from 6 qualitative studies, 2 mixed methods studies). The synthesis of included studies shows multiple sources of psychosocial burden for parents of children and adolescents affected by SMA: Most studies found reduced levels of quality of life, moderate to high levels of caregiver burden and distress, as well as physical and mental health symptoms. Further, findings indicate several unmet family needs regarding information, care coordination, treatment decisions, financial support, and adequate supportive care services.
CONCLUSION
Parents of children and adolescents with SMA face multiple sources of psychosocial stressors, caregiver burden and various unmet family needs. To unburden families, the needs of parents as caregivers should be included in integrated care paths for SMA to improve their psychosocial situation and thus their ability to care for their children and to treat or prevent physical and mental health problems due to overburdening. Future research should focus not only on quality of life and on caregiving-related burden but should also examine the clinical relevance of reported symptoms to support the implementation of adequate support services for families affected by SMA.
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10.1186/s13023-022-02407-5
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pubmed_603_4623
|
BACKGROUND
Cholesterol granulomas (CGs) of the petrous apex (PA) are rare, benign, expanding lesions. Surgical treatment is recommended for patients with symptomatic disease; however, the optimal surgical procedure is still controversial due to high recurrence rates. The main treatment strategy is divided into drainage and complete resection.
OBJECTIVE
We advocate radical resection of the lesion by the middle fossa approach and reconstruction with a vascularized galeofascial flap.
METHODS
A 10-year retrospective case review of 17 patients undergoing surgical treatment of PA CGs between 2000 and 2010 was undertaken. Operative outcomes and surgical complications were analyzed. In addition, our operative method and the related anatomy are described from cadaveric dissections.
RESULTS
All but 1 patient was operated on via a middle fossa approach. Using the middle fossa approach, radical resection of all PA CGs was achieved with obliteration of the cyst cavity using a vascularized flap. Important surrounding structures included the internal auditory canal, cochlea, petrous carotid artery, and abducens nerve. There was 1 death caused by internal carotid artery occlusion. No other major complications or cranial nerve deficits occurred postoperatively. Clinical recurrence occurred in 1 patient (5.9%).
CONCLUSION
Our technique of radical resection and reconstruction with a vascularized flap has the advantage of being less invasive with less cosmetic deformity and allows preservation of cranial nerve function with a low recurrence rate. Knowledge of the surgical anatomy and the characteristics of CG is prudent because important neurovascular structures may be exposed behind the CG wall due to bony erosion.
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10.1227/NEU.0b013e3182724354
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pubmed_564_20786
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The influence of bone mineral density on the stability of transpedicle screwing was studied in the human cadaveric lumbar vertebrae. The pull-out force correlated with bone mineral density. The tilting moment (load needed to tilt the screw 4 degrees cranially at the screw-plate junction) and the cut-up force (load needed to tip the end plate up by the screw) correlated with bone mineral density. A correlation was also found between the maximum insertion torque of the screw and bone mineral density. The maximum insertion torque correlated with the pull-out force, the tilting moment, and the cut-up force. In the cyclic tilting test (200 cycles), the mean value of the tilting moment at the 200th cycle was 67.4 +/- 6.1%, compared with the first cycle. The results suggest that preoperative measurement of BMD is necessary for transpedicle screwing in osteoporotic cases, and that the cyclic tilting motion decrease its mechanical stability. The authors have also concluded that the maximum insertion torque could predict the mechanical stability.
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10.1097/00007632-199311000-00016
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pubmed_902_3746
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A modified electrospinning process has been utilized to align magnetite (Fe(3)O(4)) nanoparticles inside highly oriented poly(ethylene oxide) nanofibers. The structural characterization of the fiber encapsulated nanoparticle arrays via electron microscopy has been detailed, and the magnetic behavior has been studied using vibrating sample magnetometry. The fiber encapsulated nanoparticle arrays exhibit orientation-dependent magnetic behavior with respect to the applied magnetic field. A strong anisotropy along orthogonal axes is obtained for aligned arrays and is manifested as a notable increase in the coercivity and remanence magnetization in the parallel field configuration. The magnetic behavior of isotropic fibers is also examined as a reference and no orientation dependence is observed. The results were found to corroborate theoretical predictions from the chain-of-spheres model. Such hybrid nanoparticle arrays may find relevance in applications requiring an orientation-dependent physical response and in the directional transfer of signals.
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10.1088/0957-4484/21/8/085707
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pubmed_411_10967
|
OBJECTIVE
To identify the impact of sociodemographic and health variables on the age at which patients undergo cleft lip repair, cleft palate repair, and primary speech evaluation.
DESIGN
A retrospective, noninterventional quality assessment, and quality improvement study was designed.
SETTING
This institutional study was performed at Michigan Medicine in Ann Arbor, MI.
PATIENTS
All patients born between 2011 and 2014 who received surgical cleft repair, excluded those who were adopted (n = 165).
MAIN OUTCOME MEASURE
The age at which patients undergo cleft lip repair, cleft palate repair, and primary speech evaluation.
RESULTS
Cleft lip repair was performed significantly later for patients identifying as Asian (18 weeks, P = .01), patients with Child Protective Services contact (19 weeks, P = .01), patients with a significant comorbidity (14 weeks, P = .02), and patients who underwent preliminary lip adhesion surgery (19 weeks, P < .01). Cleft palate repair was performed significantly later for patients identifying racially as Asian (19 weeks, P = .03) and other (22 weeks, P = .03). Preliminary speech and language evaluation were performed significantly later for patients identifying as black (55 weeks, P = .03) and patients diagnosed with an isolated cleft lip (71 weeks, P < .01).
CONCLUSIONS
Timing of cleft lip, cleft palate repair, and primary speech and language evaluation are subject to variation which may be predicted by clinically accessible factors. By identifying race, Child Protective Services contact, and care variables as significant predictors of increased patient age at time of intervention, multidisciplinary cleft care teams can proactively allocate patient support resources.
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10.1177/1055665620949119
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pubmed_260_20580
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In the photochemical cycle of bacteriorhodopsin, the light-driven proton pump of halobacteria, only the first step, the isomerization of the all-trans retinal to 13-cis, is dependent on illumination. Because the steps that accomplish the translocation of a proton during the ensuing reaction sequence of intermediate states are thermal reactions, they have direct analogies with such steps in other ion pumps. In a surprisingly large number of cases, the reactions of the photocycle could be studied without using light. This review recounts experiments of this kind, and what they contribute to understanding the transport mechanism of this pump, and perhaps indirectly other ion pumps as well.
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10.1159/000099642
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pubmed_68_8034
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We determined the accuracy and sensitivity of scalp-sphenoidal EEG for seizure focus localization in 50 patients who became seizure-free or had rare seizures following temporal lobectomy. EEG localization was based on concordant interpretations of scalp-sphenoidal ictal EEG by three independent interpreters. All patients became seizure-free or had rare seizures following temporal lobectomy. Localization from EEG disagreed with the side of surgery in only 1 (2%) of 50 patients. We identified 3 distinct patient groups with a low, moderate, and high likelihood of having a focal ictal EEG pattern during a seizure. These groups comprised 31% (low likelihood), 44% (moderate likelihood), and 25% (high likelihood) of patients. A model based on these results suggests that with multiple ictal EEG recordings, accurate localization from scalp-sphenoidal EEG is possible in approximately up to 65-70% of patients with temporal lobe epilepsy.
|
10.1097/00004691-199403000-00006
|
pubmed_636_11274
|
OBJECTIVE
To investigate the effect of bufalin on nucleus-mitochondria localization of human telomerase reverse transcriptase(hTERT) by exploring its effect on proliferation and apoptosis in human esophageal squamous carcinoma EC9706 cells.
METHODS
EC9706 cells were treated with bufalin at various concentrations, and then the cell growth inhibition of EC9706 cells was examined by CCK-8 assay and the 50% inhibitory concentration (IC(50)) was calculated.Cell cycle analysis was performed by flow cytometry with PI staining, and nucleus morphology of apoptosis were observed by fluorescence microscopy with Hoechst 33342 staining. The apoptotic index was measured by flow cytometry with Annexin V-FITC/PI double staining. hTERT subcellular localization and protein expression were determined by Western blotting and multiple immunofluorescence labling combined with laser confocal scanning microscopy.
RESULTS
The proliferation of EC 9706 cells was significantly inhibited by bufalin along with the increase of processing time and concentrations (p<0.01). After the EC9706 cells were exposed to 100 nmol/L bufalin,the number of cells gradually decreased in G(1) phase and increased in S and G(2)/M phases(p<0.05). The typical nucleus morphological changes of apoptosis were observed and the apoptotic index was increased(p<0.01). The expression of hTERT decreased in nucleus but increased in mitochondria(p<0.05).
CONCLUSIONS
Bufalin can inhibit the proliferation of human esophageal squamous carcinoma EC9706 cells in a time- and dose-dependent manner. It can arrest cell cycle in S and G(2)/M phases and induce the apoptosis of EC 9706 cells. hTERT is localized in both nucleus and mitochondria,and can be partially translocated from nucleus to mitochondria during the bufalin-induced apoptosis.
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10.3881/j.issn.1000-503X.2012.06.004
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pubmed_594_10185
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The reciprocal interaction in the forearm flexor in the human subjects were determined in the time of passive and active rest, using H-reflex testing. H-reflex was evoked by stimulation of n. medianus after 1, 10 and 150 ms after conditioned stimulus. The maximum of reciprocal inhibition was found on the beginning of passive rest; however, recover motoneurones activity coincided in the suppression of this inhibition. The recovery of motoneurones' responses during active rest was realized through increase of three phases of reciprocal inhibition. The possible mechanisms of the studied phenomenon were discussed.
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pubmed_594_10185
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pubmed_1053_4420
|
A simple specific method for the determination of vitamin C has been investigated by elucidating the reaction mechanism of its oxidation with cerium(IV) in sulphuric acid media. The reaction kinetics and rate measurements which form the basis of this method were determined by following the decrease of the intense yellow colour of cerium(IV) at 405 nm. The fixed-time and fixed-concentration methods were investigated. The former was found to be more precise and was consequently used for the determination. Advantages of this method over the B.P. and other methods are discussed.
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10.1016/0731-7085(90)80048-t
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pubmed_149_14350
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Tumor microenvironment is particularly enriched with extracellular ATP (eATP), but conflicting evidence has been provided on its functional effects on tumor growth and vascular remodeling. We have previously shown that high eATP concentrations exert a strong anti-migratory, antiangiogenic and normalizing activity on human tumor-derived endothelial cells (TECs). Since both metabotropic and ionotropic purinergic receptors trigger cytosolic calcium increase ([Ca2+]c), the present work investigated the properties of [Ca2+]c events elicited by high eATP in TECs and their role in anti-migratory activity. In particular, the quantitative and kinetic properties of purinergic-induced Ca2+ release from intracellular stores and Ca2+ entry from extracellular medium were investigated. The main conclusions are: (1) stimulation of TECs with high eATP triggers [Ca2+]c signals which include Ca2+ mobilization from intracellular stores (mainly ER) and Ca2+ entry through the plasma membrane; (2) the long-lasting Ca2+ influx phase requires both store-operated Ca2+ entry (SOCE) and non-SOCE components; (3) SOCE is not significantly involved in the antimigratory effect of high ATP stimulation; (4) ER is the main source for intracellular Ca2+ release by eATP: it is required for the constitutive migratory potential of TECs but is not the only determinant for the inhibitory effect of high eATP; (5) a complex interplay occurs among ER, mitochondria and lysosomes upon purinergic stimulation; (6) high eUTP is unable to inhibit TEC migration and evokes [Ca2+]c signals very similar to those described for eATP. The potential role played by store-independent Ca2+ entry and Ca2+-independent events in the regulation of TEC migration by high purinergic stimula deserves future investigation.
|
10.3390/cancers11060766
|
pubmed_1109_19429
|
Curcumin (diferuloylmethane), the active ingredient in the eastern spice turmeric (Curcuma longa), has been shown to inhibit the activities of numerous enzymes and signaling molecules involved in cancer, bacterial and viral infections and inflammatory diseases. We have investigated the inhibitory activities of curcumin and chemically modified curcumin (CMC) derivatives toward lethal factor (LF), the proteolytic component of anthrax toxin produced by the bacterium Bacillus anthracis. Curcumin (Compound 1) appears to inhibit the catalytic activity of LF through a mixture of inhibitory mechanisms, without significant compromise to the binding of oligopeptide substrates, and one CMC derivative in particular, Compound 3 (4-phenylaminocarbonylbis-demethoxycurcumin), is capable of inhibiting LF with potency comparable with the parent compound, while also showing improved solubility and stability. The quantitative reduction in catalytic activity achieved by the different CMC derivatives appears to be a function of the proportion of the multiple mechanisms through which they inhibit the enzyme.
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10.3109/14756366.2013.837901
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pubmed_293_4242
|
BACKGROUND
Preclinical studies have demonstrated that maternal inflammation or neonatal hyperoxia adversely affects kidney maturation. This study explored whether prenatal lipopolysaccharide (LPS) exposure can augment neonatal hyperoxia-induced kidney injury.
METHODS
Pregnant Sprague-Dawley rats received intraperitoneal injections of LPS (0.5 mg/kg) in normal saline (NS) or NS on 20 and 21 days of gestation. The pups were reared in room air (RA) or 2 weeks of 85% O2, creating the four study groups, NS + RA, NS + O2, LPS + RA, and LPS + O2. Kidneys were taken for oxidase stress and histological analyses.
RESULTS
The rats exposed to maternal LPS or neonatal hyperoxia exhibited significantly higher kidney injury score, lower glomerular number, higher toll-like receptor 4 (TLR4), myeloperoxidase (MPO), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) expressions, and higher MPO activity compared with the rats exposed to maternal NS and neonatal RA. The rats exposed to both maternal LPS and neonatal hyperoxia exhibited significantly lower glomerular number, higher kidney injury score, TLR4, MPO, and 8-OHdG expressions compared with the rats exposed to maternal LPS or neonatal hyperoxia.
CONCLUSION
Maternal inflammation exacerbates neonatal hyperoxia-induced kidney injury and the underlying mechanism may be related to activation of TLR4 and increased oxidative stress.
|
10.1038/s41390-019-0413-9
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pubmed_377_1215
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Gold nanoshells have been intensively investigated and applied to various biomedical fields because of their flexible optical tunability and biological compatibility. They hold great potential to serve as luminescent contrast agents excitable with near-infrared (NIR) lasers. In this paper, we describe the development of nanoshells with a peak of plasmon resonance at 800 nm and their subsequent use for in vivo blood vessel imaging using two-photon excitation microscopy at an excitation wavelength of 750 nm. We were able to image single nanoshell particles in blood vessels and generate optical contrast for blood vessel structure using luminescent signals. These results confirm the feasibility of engineering nanoshells with controlled optical properties for single-particle-based in vivo imaging.
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10.1088/0957-4484/22/36/365102
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pubmed_1053_21366
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Twenty volunteers with normal noses were studied to determine the effect of phenylephrine on nasal ciliary function. In vivo study of this drug was performed in 15 patients and revealed a significant increase in their ciliary beat frequency from a control of 11 Hz to 12.03 Hz (p = 0.001). Mucociliary transit times in these volunteers were also studied, revealing a mean of 9.9 minutes prestimulation and 10.2 minutes poststimulation, which was not statistically significant (p = 0.77). Five additional subjects donated ciliated mucosal samples for in vitro analysis of varying concentrations of this agent that showed a significant ciliostimulatory effect at lower concentrations (0.01%), with a progressive cilioinhibitory effect at higher concentrations (0.25%, 0.5%). The 0.05% concentration showed no significant change in ciliary activity compared to control measurements. These data demonstrate that phenylephrine has a ciliostimulatory effect in vivo, as well as in appropriate concentrations in vitro, and should be safe and relatively nontoxic to the mucociliary apparatus for short-term use.
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10.1177/019459989010300406
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pubmed_527_560
|
UNLABELLED
SUMMAR OBJECTIVES: To find the detection rate of prostate cancer (PCa) in our population with PSA values between 2.6 and 4 ng/ml.
METHODS
We included 33 consecutive patients with a median age of 66 years, that had a Transrectal Ultrasound (TRUS) guided biopsy with PSA between 2.6-4 ng/ml. Patients were divided into 2 groups. Group 1: patients with normal Digital Rectal Examination (DRE) and Group 2: Patients with DRE with asymmetry not definitive of PCa.
EXCLUSION CRITERIA
known history of PCa, intraepithelial neoplasia or Positive DRE. Statistical analysis/ Chi square, t-student and Fischer exact test.
RESULTS
Twenty eight percent of the patients had positive biopsy for PCa. Fifty six percent were Gleason 6 and 44% Gleason 7. Group 1 had 59%(20) and Group 2 41% (13) in. In Group 1 16% had positive biopsy for PCa vs 46% in group 2 (p 0.04) RR 3.07.
CONCLUSIONS
There are traces that the detection rate in our population could be lower in comparison with what has been reported in the literature. DRE is crucial in the initial evaluation; asymmetry could increase 3 fold the risk of having PCa.
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pubmed_527_560
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pubmed_602_19347
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An unplanned pregnancy is a crisis in a woman's life. She may request assistance from the health care provider in reviewing her options of becoming a parent, continuing the pregnancy and placing her baby for adoption, or terminating the pregnancy. To facilitate the decision-making process for women facing these choices, the clinician must first examine her own values and biases. To aid the clinician in providing nonjudgmental and nondirective counseling, this article provides factual information about abortion and adoption, values clarification exercises, and concrete approaches to help women examine their beliefs.
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10.1016/j.jmwh.2004.01.002
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pubmed_128_21794
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BACKGROUND
Emotional blunting is a characteristic feature of behavioral variant frontotemporal dementia (bvFTD) and can help discriminate between patients with bvFTD and other forms of younger-onset dementia.
OBJECTIVE
We compared the presence of emotional blunting symptoms in patients with bvFTD and early-onset Alzheimer's disease (AD), and investigated the neuroanatomical associations between emotional blunting and regional brain volume.
METHODS
Twenty-five individuals with bvFTD (n = 11) and early-onset AD (n = 14) underwent magnetic resonance imaging (MRI) and were rated on symptoms of emotional blunting using the Scale for Emotional Blunting (SEB). The two groups were compared on SEB ratings and MRI-derived brain volume using tensor-based morphometry. Voxel-wise linear regression was performed to determine neuroanatomical correlates of SEB scores.
RESULTS
The bvFTD group had significantly higher SEB scores compared to the AD group. On MRI, bvFTD patients had smaller bilateral frontal lobe volume compared to AD patients, while AD patients had smaller bilateral temporal and left parietal volume than bvFTD patients. In bvFTD, SEB ratings were strongly correlated with right anterior temporal volume, while the association between SEB and the right orbitofrontal cortex was non-significant.
CONCLUSIONS
Symptoms of emotional blunting were more prevalent in bvFTD than early-onset AD patients. These symptoms were particularly associated with right-sided atrophy, with significant involvement of the right anterior temporal region. Based on these findings, the SEB appears to measure symptoms of emotional blunting that are localized to the right anterior temporal lobe.
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10.3233/JAD-132219
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pubmed_471_13892
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In the pathophysiology of Alzheimer's disease (AD), the deposition of amyloid β protein (Aβ) is associated with oxidative stress, leading to cognitive impairment and neurodegeneration. Betaine (glycine betaine or trimethylglycine), known as an osmolyte and methyl donor in mammalian cells, has been reported to suppress the proinflammatory response and oxidative stress in the kidneys, but the effects of betaine on brain diseases remain to be determined. Here, to investigate the effects of betaine treatment on cognitive impairment and the increase in oxidative stress in the brain of an AD animal model, we performed a novel object recognition test and measured the malondialdehyde (MDA; a marker of oxidative stress) levels in the frontal cortex and hippocampus of mice intracerebroventricularly injected with Aβ25-35, an active fragment of Aβ. Betaine prevented cognitive impairment as well as increases of the cortical and hippocampal MDA levels in Aβ25-35-injected mice. Of note, NNC 05-2090, a selective inhibitor of betaine/GABA transporter-1 (GAT2/BGT-1), reduced the preventive effects of betaine on Aβ25-35-induced cognitive impairment without affecting the increased MDA levels in the brain of Aβ25-35-injected mice. As betaine is used as a substrate of GAT2/BGT-1, these results suggest that betaine is transported through GAT2/BGT-1 and prevents cognitive impairment in Aβ25-35-injected mice, but GAT2/BGT-1 function is not required for the antioxidant effects of betaine.
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10.1016/j.ejphar.2018.10.037
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pubmed_217_20291
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An ambiguous figure such as the Necker cube causes spontaneous perceptual switching (SPS). The mechanism of SPS in multistable perception has not yet been determined. Although early psychological studies suggested that SPS may be caused by fatigue or satiation of orientation, the neural mechanism of SPS is still unknown. Functional magnetic resonance imaging (fMRI) has shown that the dorsal attention network (DAN), which mainly controls voluntary attention, is involved in bistable perception of the Necker cube. To determine whether neural dynamics along the DAN cause SPS, we performed simultaneous electroencephalography (EEG) and fMRI during an SPS task with the Necker cube, with every SPS reported by pressing a button. This EEG-fMRI integrated analysis showed that (a) 3-4 Hz spectral EEG power modulation at fronto-central, parietal, and centro-parietal electrode sites sequentially appeared from 750 to 350 ms prior to the button press; and (b) activations correlating with the EEG modulation traveled along the DAN from the frontal to the parietal regions. These findings suggest that slow oscillation initiates SPS through global dynamics along the attentional system such as the DAN.
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10.1007/s11571-012-9196-y
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pubmed_494_9541
|
Fungal infections caused by the members of the genera Pseudallescheria and/or Scedosporium are important complications in patients after near-drowning. As the taxonomy of Pseudallescheria and Scedosporium has been revised, clinical isolates from 11 patients, after near-drowning, previously identified as P. boydii or S. apiospermum had to be re-identified. S. apiospermum, now separated from P. boydii as a distinct species, was found most frequently (n = 8), while S. aurantiacum, recently described as new species and P. boydii were less common (n = 2 and n = 1, respectively). Three patients near-drowned during the Tsunami 2004 were infected by different species of the P. boydii complex. In vitro testing resulted in lowest minimal inhibitory concentration (MICs) for voriconazole (range 0.25-2.0 microg ml(-1)).
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10.1111/j.1439-0507.2008.01579.x
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pubmed_997_6767
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The human-specific gene ARHGAP11B has been implicated in human neocortex expansion. However, the extent of ARHGAP11B's contribution to this expansion during hominid evolution is unknown. Here we address this issue by genetic manipulation of ARHGAP11B levels and function in chimpanzee and human cerebral organoids. ARHGAP11B expression in chimpanzee cerebral organoids doubles basal progenitor levels, the class of cortical progenitors with a key role in neocortex expansion. Conversely, interference with ARHGAP11B's function in human cerebral organoids decreases basal progenitors down to the chimpanzee level. Moreover, ARHGAP11A or ARHGAP11B rescue experiments in ARHGAP11A plus ARHGAP11B double-knockout human forebrain organoids indicate that lack of ARHGAP11B, but not of ARHGAP11A, decreases the abundance of basal radial glia - the basal progenitor type thought to be of particular relevance for neocortex expansion. Taken together, our findings demonstrate that ARHGAP11B is necessary and sufficient to ensure the elevated basal progenitor levels that characterize the fetal human neocortex, suggesting that this human-specific gene was a major contributor to neocortex expansion during human evolution.
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10.1101/2020.10.01.322792
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pubmed_31_10984
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Chemical, physical and mechanical methods of nanomaterial preparation are still regarded as mainstream methods, and the scientific community continues to search for new ways of nanomaterial preparation. The major objective of this review is to highlight the advantages of using green chemistry and bionanotechnology in the preparation of functional low-cost catalysts. Bionanotechnology employs biological principles and processes connected with bio-phase participation in both design and development of nano-structures and nano-materials, and the biosynthesis of metallic nanoparticles is becoming even more popular due to; (i) economic and ecologic effectiveness, (ii) simple one-step nanoparticle formation, stabilisation and biomass support and (iii) the possibility of bio-waste valorisation. Although it is quite difficult to determine the precise mechanisms in particular biosynthesis and research is performed with some risk in all trial and error experiments, there is also the incentive of understanding the exact mechanisms involved. This enables further optimisation of bionanoparticle preparation and increases their application potential. Moreover, it is very important in bionanotechnological procedures to ensure repeatability of the methods related to the recognised reaction mechanisms. This review, therefore, summarises the current state of nanoparticle biosynthesis. It then demonstrates the application of biosynthesised metallic nanoparticles in heterogeneous catalysis by identifying the many examples where bionanocatalysts have been successfully applied in model reactions. These describe the degradation of organic dyes, the reduction of aromatic nitro compounds, dehalogenation of chlorinated aromatic compounds, reduction of Cr(VI) and the synthesis of important commercial chemicals. To ensure sustainability, it is important to focus on nanomaterials that are capable of maintaining the important green chemistry principles directly from design inception to ultimate application.
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10.1016/j.biotechadv.2018.11.012
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pubmed_667_19771
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Kingella denitrificans possess type-4 pili, and the type strain, ATCC 33394, contains at least four complete copies of type-4 pilin-encoding genes. Previously reported hybridization patterns of K. denitrificans chromosomal DNA seen using a Neisseria gonorrhoeae pilin gene region probe, had been interpreted as representing possible partial, silent gene loci. This now appears to be due to cross-reaction to multiple copies of 18-bp inverted repeat structures. Data are presented on a variety of colony variants which have changed from a spreading-corroding (SC) phenotype to a nonspreading-noncorroding (N) phenotype. Interestingly, while the SC to N transition is most often associated with loss of piliation in other bacteria containing type-4 pili, many of the K. denitrificans N variants still produce pilin, and some still produce pili.
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10.1016/s0378-1119(96)00828-1
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pubmed_567_717
|
A new simple, accurate, precise and sensitive indirect method for the determination of pindolol HCl (1), propranolol HCl (2) and levamisole HCl (3) using atomic absorption spectrometry has been developed. The method is based on precipitation of the ion associates formed from the reaction of (1), (2) or (3) with manganese thiocyanate and/or potassium ferricyanide. The solubility of the solid complexes at the optimum conditions of pH and ionic strength values have been studied. Saturated solutions of each ion-associate were prepared under the optimum conditions and the metal ion content in the supernatant was determined. The method has been used for the determination of 1.14-17.07, 1.18-17.75 and 1.08-16.24 microg/ml of (1), (2) and (3), respectively using manganese thiocyanate and 1.71-25.60, 1.77-26.62 and 1.62-24.36 microg/ml of (1), (2) and (3), respectively using potassium ferricyanide. The method developed applied for analysis of bulk drugs and some of their pharmaceutical preparations.
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10.1016/s0731-7085(99)00240-x
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pubmed_20_16188
|
Versican is an extracellular matrix (ECM) molecule that interacts with other ECM components to influence ECM organization, stability, composition, and cell behavior. Versican is known to increase in a number of cancers, but little is known about how versican influences the amount and organization of the ECM components in the tumor microenvironment. In the present study, we modulated versican expression using siRNAs in the human leiomyosarcoma (LMS) smooth muscle cell line SK-LMS-1, and observed the formation of elastin and elastic fibers in vitro and also in vivo in a nude mouse tumor model. Constitutive siRNA-directed knockdown of versican in LMS cells resulted in increased levels of elastin, as shown by immunohistochemical staining of the cells in vitro, and by mRNA and protein analyses. Moreover, versican siRNA LMS cells, when injected into nude mice, generated smaller tumors that had significantly greater immunohistochemical and histochemical staining for elastin when compared to control tumors. Additionally, microarray analyses were used to determine the influence of versican isoform modulation on gene expression profiles, and to identify genes that influence and relate to the process of elastogenesis. cDNA microarray analysis and TaqMan low density array validation identified previously unreported genes associated with downregulation of versican and increased elastogenesis. These results highlight an important role for the proteoglycan versican in regulating the expression and assembly of elastin and the phenotype of LMS cells.
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pubmed_20_16188
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pubmed_750_8884
|
A magnetic molecularly imprinted composite was prepared by reverse microemulsion using carbon dots (CDs), Fe3O4 as the co-nucleus, and a molecularly imprinted polymer (MIP; with 2,4,6-trinitrophenol as the template) acting as recognition sites. The composite of type CD/Fe3O4@MIPs was characterized by transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), Fourier transform infrared spectroscopy (FT-IR), zeta potentiometric analysis, X-ray diffraction (XRD) and vibrating sample magnetometry (VSM). The results showed that the composite MIP has a spherical shape with average diameter of 200 nm. They also showed that the composite contains core-shell structures with several Fe3O4 nanoparticles and CDs embedded in each of the microsphere. The composite can extract 2,4,6-trinitrophenol (TNP) and has an imprinting factor of 3.6. It has high selectivity and sensitivity for TNP which acts as a quencher of the fluorescence of the CDs (with excitation/emission maxima at 370/470 nm). The limit of detection of this fluorometric TNP assay is 0.5 nM. The method was successfully applied to the determination of TNP in spiked tap water and river water samples, and recoveries ranged from 89.4% to 108.5% (with an RSD of <6%). Graphical abstract Schematic representation of the magnetic molecularly imprinted composite containing fluorescent carbon dots, Fe3O4 and molecularly imprinted polymer (CD/Fe3O4@MIPs). The CD/Fe3O4@MIPs were applied to the selective and sensitive detection of 2,4,6-trinitrophenol (TNP) by fluorometry.
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10.1007/s00604-018-3200-0
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pubmed_370_8441
|
The rational management of the palpable breast lump requires a tissue diagnosis. The more conventional approach is biopsy under general anesthesia, examination of frozen sections and "follow-on" mastectomy when indicated. In the present study, we aimed at arriving at an unequivocal tissue diagnosis by studying permanent sections at a separate ambulatory procedure either with formal biopsy under local anesthetic or, in suspicious lumps, with the Trucut biopsy needle (Travenol Laboratories, Inc. USA). Only 7 (14%) of the 56 women with 64 breast lumps were hospitalized for biopsy under general anesthesia. In 13 out of 22 breast cancers, the definitive diagnosis was made by examining Trucut needle biopsy specimens. This alternative approach provides a significant reduction of costs, more efficient utilization of operating time and a fully evaluated, psychologically prepared patient, when mastectomy is indicated.
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pubmed_370_8441
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pubmed_623_17585
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OBJECTIVES
To report epidemiology and characteristics of urinary lithiasis and its management in kidney allograft at the time of organ procurement or after kidney transplantation.
MATERIAL AND METHODS
An exhaustive systematic review of the scientific literature was performed in the Medline database (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) using different associations of the following keywords (MESH): urinary lithiasis, stone, kidney transplantation. Publications obtained were selected based on methodology, language, date of publication (last 10 years) and relevance. Prospective and retrospective studies, in English or French, review articles; meta-analysis and guidelines were selected and analyzed. This search found 58 articles. After reading, 37 were included in the text based on their relevance.
RESULTS
Frequency of urinary lithiasis in renal transplant recipient is similar to those observed in the general population. Generally, urinary lithiasis of the graft is asymptomatic because of renal denervation after organ procurement and transplantation. Nevertheless, this situation may be at high risk due to the immunosuppressed state of the recipient with a unique functioning kidney. Most of the time, the diagnosis is incidental during routine post-transplantation follow-up. Management of urolithiasis in renal transplant recipient is similar to that performed in general population.
CONCLUSION
Due to its potential severity in transplanted immunosuppressed patients with a sole kidney, urolithiasis requires expert urological management.
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10.1016/j.purol.2016.08.012
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pubmed_452_12225
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HemoDose is a software tool, which estimates absorbed doses based on blood cell counts (BCC). The aim of our study was to validate HemoDose for early dose estimates. Dose estimates generated by HemoDose were compared with dose estimates stored in SEARCH from radiation victims. Moreover, BCC from unirradiated donors and corresponding HemoDose dose estimates were analysed. We employed linear or logistic regression analysis. There was a significant correlation between calculated doses by HemoDose based on single and multiple lymphocyte counts when omitting lowest and highest dose estimates. Furthermore, there was a significant correlation between calculated doses by HemoDose based on lymphocyte counts and the estimated doses based on DIC. The dose estimates by HemoDose based on lymphocyte counts and DIC showed a comparable correlation with HARS degrees 0 and 4. In conclusion, HemoDose dose estimation based on early lymphocyte counts appears to be a promising biodosimetry tool under certain considerations.
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10.1093/rpd/ncaa063
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pubmed_285_10361
|
BACKGROUND
Elimination of lymphatic filariasis (LF) in Samoa continues to be challenging despite multiple annual mass drug campaigns aimed at stopping transmission by reducing the prevalence and density of microfilaraemia. The persistence of transmission may be partly related to the highly efficient Aedes vectors. The assessment of pathogen transmission by mosquito vectors and of vector control relies on the ability to capture mosquitoes efficiently. The aims of this study are to compare trapping methods to capture LF-infected mosquitoes and determine the role in transmission of the species of Aedes mosquitoes in the area.
METHODS
Fasitoo-Tai village was the chosen site because of persistent transmission despite annual mass drug administration. Sampling methods included BioGents Sentinel (BGS) trap, human-baited collections (HBC) and the Centers for Disease Control (CDC) trap. BGS and CDC traps were baited with BG-lure, CO2, and/or octenol. Individual trap locations were geo-located and efficiency of sampling methods was evaluated using a randomized Latin-square design in two locations. Number of mosquitoes collected (male and female), as well as species for each trapping method were determined. Additionally, Ae. polynesiensis and Ae. (Finlaya) spp. females were pooled by trap method and analysed for filarial DNA. Infection prevalence was estimated using the PoolScreen software.
RESULTS
The BGS trap with any type of bait collected more mosquitoes compared to both the CDC trap and the HBC. The BGS trap baited with BG-lure collected more mosquitoes than with CO2 and octenol. There were no significant differences between trapping methods in terms of proportions of infected females collected. The prevalence of filarial infection in Ae. polynesiensis and Ae. (Finlaya) spp. was estimated at 4.7% and 0.67% respectively.
CONCLUSIONS
This study supports the use of the BGS trap for research on and surveillance of the mosquito vectors of LF in Samoa. The BGS trap is a suitable and safer alternative to HBC for sampling Ae. polynesiensis and Ae. (Finlaya) spp., which continue to be the predominant vectors of LF. Of concern was the high prevalence of LF in mosquitoes despite a recent mass drug administration programme. This highlights the urgency for updated policies concerning filariasis elimination in Samoa.
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10.1186/s13071-015-0886-2
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pubmed_339_21234
|
Asthma is a complex genetic disease with multiple genes involved in the pathogenesis. Some of these genes have been investigated to determine whether they influence an individual's response to asthma medication. We summarise the recent developments in the genetics of asthma as they pertain to the three main treatments available - inhaled glucocorticoids (GCs), (2)-agonists and leukotriene modulators. It has been shown that polymorphisms in the (2)-adrenergic receptor ((2)AR) gene influence responsiveness to (2)-agonists. Polymorphisms in the 5-lipoxygenase (5-LO) gene and the leukotriene C(4) (LTC4) synthase gene have been associated with response to medications that target the LT pathway. However, no polymorphisms have been identified that influence response to anticholinergics or are involved in steroid resistance. In the future, knowledge of an individual's genotype may help us tailor treatment to make it the most appropriate form for that asthmatic individual.
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10.1517/14622416.2.4.329
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pubmed_810_10308
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MR imaging at high magnetic fields benefits from an increased signal-to-noise ratio; however T(1)-based MR contrast agents show decreasing relaxivity (r(1)) at higher fields. High field, high relaxivity contrast agents can be designed by carefully controlling the rotational dynamics of the molecule. To this end, we investigated applications of the alanine analogue of Gd(DOTA), Gd(DOTAla). Fmoc-protected DOTAla suitable for solid phase peptide synthesis was synthesized and integrated into polypeptide structures. Gd(III) coordination results in very rigid attachment of the metal chelate to the peptide backbone through both the amino acid side chain and coordination of the amide carbonyl. Linear and cyclic monomers (GdL1, GdC1), dimers (Gd(2)L2, Gd(2)C2), and trimers (Gd(3)L3, Gd(3)C3) were prepared and relaxivities were determined at different field strengths ranging from 0.47 to 11.7 T. Amide carbonyl coordination was indirectly confirmed by determination of the hydration number q for the EuL1 integrated into a peptide backbone, q = 0.96 ± 0.09. The water residency time of GdL1 at 37 °C was optimal for relaxivity, τ(M) = 17 ± 2 ns. Increased molecular size leads to increased per Gd relaxivity (from r(1) = 7.5 for GdL1 to 12.9 mM(-1) s(-1) for Gd(3)L3 at 1.4 T, 37 °C). The cyclic, multimeric derivatives exhibited slightly higher relaxivities than the corresponding linearized multimers (Gd(2)C2: r(1) = 10.5 mM(-1) s(-1) versus Gd(2)C2-red r(1) = 9 mM(-1) s(-1) at 1.4 T, 37 °C). Overall, all six synthesized Gd complexes had higher relaxivities at low, intermediate, and high fields than the clinically used small molecule contrast agent [Gd(HP-DO3A)(H(2)O)].
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10.1021/ja309187m
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pubmed_469_5810
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In this work, we have explored a novel application of one-dimensional (1D) photonic crystals (PCs) as a biomarker for the detection of organic materials in wastewater. The high concentration of organic materials may lead to adverse impact on human life. In order to save human life from these adverse effects, we have investigated the bio-alcohol sensing properties of a 1D multilayer periodic structure (AB) capable of detecting organic materials in wastewater. The proposed structure works on the principle to detect a very small change in the refractive index of the wastewater sample under investigation by means of producing a shift in the position of the defect mode inside the photonic band gap (PBG) of the proposed structure. The transfer matrix method (TMM) has been used to investigate the transmission properties of the proposed design with the help of MATLAB software. We have also studied the effect of changes in the defect layer's thickness, the volume fraction of the nanocomposite material and the incident angle on the sensitivity of our proposed bio-alcohol sensing design. Our bio-alcohol sensor shows a high sensitivity value of 500 nm/RIU and a low detection limit value of 1 × 10-5 RIU. The figure of merit and quality factor values of our bio-alcohol sensor are 5 × 103 and 5.236 × 103, respectively. The damping rate of the design is ξ=95.4927×10-5.
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10.3390/ma15114012
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pubmed_575_2797
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Protecting molecular structures from disclosure against external parties is of great relevance for industrial and private associations, such as pharmaceutical companies. Within the framework of external collaborations, it is common to exchange datasets by encoding the molecular structures into descriptors. Molecular fingerprints such as the extended-connectivity fingerprints (ECFPs) are frequently used for such an exchange, because they typically perform well on quantitative structure-activity relationship tasks. ECFPs are often considered to be non-invertible due to the way they are computed. In this paper, we present a fast reverse-engineering method to deduce the molecular structure given revealed ECFPs. Our method includes the Neuraldecipher, a neural network model that predicts a compact vector representation of compounds, given ECFPs. We then utilize another pre-trained model to retrieve the molecular structure as SMILES representation. We demonstrate that our method is able to reconstruct molecular structures to some extent, and improves, when ECFPs with larger fingerprint sizes are revealed. For example, given ECFP count vectors of length 4096, we are able to correctly deduce up to 69% of molecular structures on a validation set (112 K unique samples) with our method.
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10.1039/d0sc03115a
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pubmed_703_13388
|
Repeat-induced point mutation (RIP) is a sexual stage-specific mutational process of Neurospora crassa and other fungi that alters duplicated DNA sequences. Previous studies from our laboratory showed that chromosome segment duplications (Dps) longer than (approx.) 300 kbp can dominantly suppress RIP, presumably by titration of the RIP machinery, and that although Dps less than 200 kbp did not individually suppress RIP, they could do so in homozygous and multiply heterozygous crosses, provided the sum of the duplicated DNA exceeds (approx.) 300 kbp. Here we demonstrate suppression of RIP in a subset of progeny carrying the normally sub-threshold 154 kbp Dp(R2394) from a cross of T(R2394) to the wild isolated Carrefour Mme. Gras strain (CMG). Thus, the CMG strain contains a factor that together with Dp(R2394) produces a synthetic RIP suppressor phenotype. It is possible that the factor is a cryptic Dp that together with Dp(R2394) can exceed the size threshold for titration of the RIP machinery and thereby causes RIP suppression.
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10.1007/s12038-011-9153-7
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pubmed_396_4120
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Several clinical laboratories in different regions of Spain have shared the search for reference individuals and the production of reference values for quantities concerning thyrotropin, non-protein bound thyroxine, triiodothyronine, cobalamines and folates, using an Elecsys 2010 analyser. All the logistic work has been done in co-operation with the supplier of the analyser (Roche Diagnostics España, S.L., Barcelona). The reference limits produced in the virtual laboratory are in fact derived from the blend of reference values obtained by each laboratory. The multicentric reference limits were estimated according to the recommendations of the International Federation of Clinical Chemistry. The work done represents a model of co-operation between the in vitro diagnostic industry and clinical laboratories for the production of reference values.
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10.1016/s0009-8981(00)00406-x
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pubmed_42_14924
|
The cytoplasmic membrane protein TonB couples the proton electrochemical potential of the cytoplasmic membrane to transport events at the outer membrane of Gram-negative bacteria. The amino-terminal signal anchor of TonB and its interaction with the cytoplasmic membrane protein ExbB are essential to this process. The TonB signal anchor is predicted to form an alpha-helix, with a conserved face comprised of residues Ser(16), His(20), Leu(27), and Ser(31). Deletion of either Ser(16) or His(20) or of individual intervening but not flanking residues rendered TonB inactive and unable to assume a proton motive force-dependent conformation. In vivo formaldehyde cross-linking experiments revealed that the ability of this subset of mutants to form a characteristic heterodimer with ExbB was greatly diminished. Replacement of residues 17-19 by three consecutive alanines produced a wild type TonB allele, indicating that the intervening residues (Val, Cys, and Ile) contributed only to spacing. These data indicated that the spatial relationship of Ser(16) to His(20) was essential to function and suggested that the motif HXXXS defines the minimal requirement for the coupling of TonB to the cytoplasmic membrane electrochemical gradient. Deletion of Trp(11) resulted in a TonB that remained active yet was unable to cross-link with ExbB. Because Trp(11) was demonstrably not involved in the actual cross-linking, these results suggest that the TonB/ExbB interaction detected by cross-linking occurred at a step in the energy transduction cycle distinct from the coupling of TonB to the electrochemical gradient.
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10.1074/jbc.M007479200
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pubmed_298_12320
|
BACKGROUND & AIMS
We evaluated the efficacy and safety of high-dose swallowed fluticasone propionate (FP) and dose reduction in patients with eosinophilic esophagitis (EoE) and analyzed esophageal transcriptomes to identify mechanisms.
METHODS
We conducted a randomized, multisite, double-blind, placebo-controlled trial of daily 1760 mcg FP in participants age 3-30 years with active EoE. Twenty-eight participants received FP, and 14 participants received placebo. After 3 months, participants given FP who were in complete remission (CR) received 880 mcg FP daily, and participants in the FP or placebo groups who were not in CR continued or started, respectively, 1760 mcg FP daily for 3 additional months. The primary end point was histologic evidence for CR. Secondary end points were partial remission (PR), symptoms, compliance, esophageal gene expression, esophageal eosinophil count, and the relationship between clinical features and FP responsiveness.
RESULTS
After 3 months, 65% of subjects given FP and no subjects given placebo were in CR (P = .0001); 12% of those given FP and 8% of those given placebo were in PR. In the FP group, 73% of subjects remained in CR, and 20% were in PR after the daily dose was reduced by 50%. Extending FP therapy in FP-resistant participants did not induce remission. FP decreased heartburn severity (P = .041). Compliance, age, sex, atopic status, or anthropomorphic features were not associated with response to FP. Gene expression patterns in esophageal tissues of FP responders were similar to those of patients without EoE; there was evidence for heterogeneous steroid signaling in subjects who did not respond to FP and preliminary evidence for transcripts predictive of FP responsiveness.
CONCLUSIONS
Daily administration of a high dose of FP induces histologic remission in 65%-77% of patients with EoE after 3 months. A 50% dose reduction remained effective in 73%-93% of patients who initially responded to FP. Nonresponders had evidence of steroid resistance; histologic and molecular markers may predict resistance. Clinicaltrials.gov number: NCT00426283.
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pubmed_298_12320
|
pubmed_13_6361
|
PURPOSE
To determine the value of structural magnetic resonance imaging (MRI) in predicting post-operative paediatric cerebellar mutism syndrome (pCMS) in children undergoing surgical treatment for medulloblastoma.
METHODS
Retrospective cohort study design. Electronic/paper case note review of all children with medulloblastoma presenting to Great Ormond Street Hospital between 2003 and 2013. The diagnosis of pCMS was established through a scoring system incorporating mutism, ataxia, behavioural disturbance and cranial nerve deficits. MRI scans performed at three time points were assessed by neuroradiologists blinded to the diagnosis of pCMS.
RESULTS
Of 56 children included, 12 (21.4%) developed pCMS as judged by a core symptom of mutism. pCMS was more common in those aged 5 or younger. There was no statistically significant difference in pre-operative distortion or signal change of the dentate or red nuclei or superior cerebellar peduncles (SCPs) between those who did and did not develop pCMS. In both early (median 5 days) and late (median 31 months) post-operative scans, T2-weighted signal change in SCPs was more common in the pCMS group (p = 0.040 and 0.046 respectively). Late scans also showed statistically significant signal change in the dentate nuclei (p = 0.024).
CONCLUSIONS
The development of pCMS could not be linked to any observable changes on pre-operative structural MRI scans. Post-operative T2-weighted signal change in the SCPs and dentate nuclei underlines the role of cerebellar efferent injury in pCMS. Further research using advanced quantitative MRI sequences is warranted given the inability of conventional pre-surgical MRI to predict pCMS.
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10.1007/s00381-018-3867-x
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pubmed_789_19893
|
Omega-3 fatty acids, such as, DHA and EPA, have well established beneficial effects on human health, but their action mechanisms remain unknown. Recent pharmacological studies have suggested several molecular targets for the anti-inflammatory effects of omega-3 fatty acids, namely, nuclear receptor PPARγ and the G protein-coupled receptor GPR120. Furthermore, the conversions of omega-3 fatty acids to anti-inflammatory and pro-resolving resolvins and protectins and the identifications of putative target GPCRs, ChemR23, BLT₁, ALX/FPR2, and GPR32, have drawn great attention. In addition, the pharmacology of omega-3 fatty acids is now under scrutiny. However, questions remain to be answered regarding the in vivo effects of omega-3 fatty acids at the molecular level. In this review, anti-inflammatory effects of omega-3 fatty acids are discussed from the viewpoint of molecular pharmacology, particularly with respect to the above-mentioned GPCRs.
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10.1016/j.plipres.2012.02.003
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pubmed_496_1639
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The study describes brain areas involved in medial temporal lobe (mTL) seizures of 12 patients. All patients showed so-called oro-alimentary behavior within the first 20 s of clinical seizure manifestation characteristic of mTL seizures. Single photon emission computed tomography (SPECT) images of regional cerebral blood flow (rCBF) were acquired from the patients in ictal and interictal phases and from normal volunteers. Image analysis employed categorical comparisons with statistical parametric mapping and principal component analysis (PCA) to assess functional connectivity. PCA supplemented the findings of the categorical analysis by decomposing the covariance matrix containing images of patients and healthy subjects into distinct component images of independent variance, including areas not identified by the categorical analysis. Two principal components (PCs) discriminated the subject groups: patients with right or left mTL seizures and normal volunteers, indicating distinct neuronal networks implicated by the seizure. Both PCs were correlated with seizure duration, one positively and the other negatively, confirming their physiological significance. The independence of the two PCs yielded a clear clustering of subject groups. The local pattern within the temporal lobe describes critical relay nodes which are the counterpart of oro-alimentary behavior: (1) right mesial temporal zone and ipsilateral anterior insula in right mTL seizures, and (2) temporal poles on both sides that are densely interconnected by the anterior commissure. Regions remote from the temporal lobe may be related to seizure propagation and include positively and negatively loaded areas. These patterns, the covarying areas of the temporal pole and occipito-basal visual association cortices, for example, are related to known anatomic paths.
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10.1002/hbm.20196
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pubmed_491_22232
|
Diesel particulate matter (DPM) is associated with adverse human health effects. This study aims to investigate the relationship between DPM exposure and emissions by estimating the individual intake fraction (iFi) and population intake fraction (iFp) of DPM. Daily average concentrations of particulate matter at two bus stops during rush hours were measured, and then they were apportioned to DPM due to heavy-duty diesel bus emissions using Chemical Mass Balance Model. The DPM emissions of diesel buses for different driving conditions (idling, creeping and traveling) were estimated on the basis of field observations and published emission factors. The median iFi of DPM was 0.67 and 1.39 per million for commuters standing at the bus stop and pedestrians/cyclists passing through the bus stop during rush hours, respectively. The median iFp of DPM was 94 per million. Estimations of iFi and iFp of DPM are potentially significant for exposure assessment and risk management.
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pubmed_491_22232
|
pubmed_935_11588
|
Conversion of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoic acid into 3 alpha, 7 alpha, 12 alpha 24-tetrahydroxy-5 beta-cholestanoic and cholic acids was catalyzed either by the mitochondrial fraction fortified with coenzyme A, ATP, MgCl2 and NAD or by the combination of microsomal fraction and 100,000 x g supernatant fluid fortified with coenzyme A, ATP and nad. 24-hydroxylation and formation of cholic acid occurred at similar rates with the 25R- and the 25S-forms of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoic acid. The 25R- and 25S-forms of 3 alpha, 7 alpha, 12 alpha-trihydroxy- and 3 alpha, 7 alpha, 12 alpha, 24-tetrahydroxy-5 beta-cholestanoic acids were administered to bile fistula rats. Labeled cholic acid was isolated from the bile. The initial specific radioactivity of cholic acid was higher and the disappearance of radioactivity more rapid after administration of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoic acid than of 3 alpha, 7 alpha, 12 alpha, 24-tetrahydroxy-5 beta-cholestanoic acid. The findings are discussed in relation to the assumed pathway for side chain cleavage in cholic acid biosynthesis.
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10.1007/BF02533886
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pubmed_658_11029
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Aerobic granulation was studied in a column-type of sequential sludge blanket reactor. Reactor was operated 4 hours per cycle under a chemical oxygen demand (COD) loading rate of 6.0 kg/m3/d by using acetate as substrate. Results showed that aerobic granules with a mean diameter of 0.35 mm were observed at cycle 42. With granulation proceeding, the sludge volume index (SVI) value gradually decreased, and to an average value of 50 mL/g at stable granulation period. Observation of granules' microstructure by scanning electron microscopy (SEM) showed that rod bacteria were dominant in granules with lots of cavities presented. An increase in cell hydrophobicity was observed after the appearance of aerobic granules. The cell hydrophobicity of sludge was found to be about 50% higher after granulation. It appears that high hydrophobicity could induce cell attachment and further strengthen cell-cell interaction; cell hydrophobicity might therefore play a major role in the formation of aerobic granules.
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pubmed_658_11029
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pubmed_845_2422
|
OBJECTIVE
A previous survey investigated postmenopausal vaginal atrophy in a sample of women across Latin America. To help implement a tailored approach to improve postmenopausal care and outcomes in Brazil, we consider results from the survey for this country.
METHODS
A total of 2509 postmenopausal women resident in Argentina, Brazil, Chile, Colombia, or Mexico completed an online questionnaire. The Brazilian cohort comprised 504 women.
RESULTS
Over half of the Brazilian cohort (56%) reported experiencing symptoms of vaginal atrophy; most described them as moderate or severe (76%), and almost half (48%) experienced symptoms for at least 1 year. Three-quarters of the Brazilian cohort (75%) were unaware of the chronic nature of the condition. Upon experiencing symptoms of vaginal atrophy, 92% had visited a health-care provider to discuss treatment options. Overall, 56% were aware of some form of local hormone therapy and 40% of those affected by vaginal atrophy had used such treatment.
CONCLUSION
Postmenopausal women in Brazil are likely to benefit from increased awareness of the symptoms of vaginal atrophy. Health-care providers can potentially improve outcomes by helping women to understand the chronic nature of the condition and available treatment options. Women may be open to education pre menopause, before symptoms occur.
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10.1080/13697137.2020.1804546
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pubmed_30_14435
|
Rats were treated for 5 to 14 days with perfluoroacetate, perfluorobutyrate and perfluorooctanoate. Alterations in hepatic morphology with special reference to the peroxisomal compartment were investigated by light and electron microscopy following cytochemical staining of catalase activity with the alkaline 3,3'-diaminobenzidine medium. All three compounds induced hepatomegaly and peroxisome proliferation. Perfluorobutyrate and perfluorooctanoate were found to be more active than perfluoroacetate. Perfluorooctanoate-induced peroxisome proliferation was more prevalent in centrilobular than in periportal hepatocytes. Peroxisomes in centrilobular liver cells frequently were of round shape, exhibited diameters of up to 1.5 microns and were predominantly located within smooth endoplasmic reticulum-glycogen areas. In periportal cells, however, clusters of polymorphous peroxisomes ranging from 250 to 1,100 nm in diameter were observed at the periphery of smooth endoplasmic reticulum-glycogen regions. Peroxisome proliferation was accompanied by a change of peroxisomal and mitochondrial enzyme activities, in particular an increase in peroxisomal palmitoyl-CoA oxidation. Significant alterations in the concentration of peroxisomal matrix and membrane polypeptides were also noted. Within the first 2 days, perfluorooctanoate treatment exerted a strong hypolipidemic activity and both compounds perfluorooctanoate and perfluorobutyrate raised the level of hepatic free acid-soluble CoA nearly 10-fold as compared with control livers. The results suggest perfluorinated carboxylic acids to be model substances suitable to correlate biochemical and morphological parameters with the zonal heterogeneity of the peroxisomal compartment in rat liver. Due to the manifold hepatic effects, contact of humans with perfluorinated carboxylic acids or their metabolic precursors may represent a severe health risk.
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10.1002/hep.1840090411
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pubmed_643_5450
|
BACKGROUND
Pain has a great impact on the physical and mental condition of hospitalized patients, reduces quality of life, and increases economic burden.
AIMS
The study aimed to determine pain prevalence, its characteristics, analgesic treatment, and associated factors for severity and chronicity of pain in hospitalized patients.
METHODS
A cross-sectional study was carried out including 847 eligible adult in-patients, aged ≥18 years, admitted to the All India Institute of Medical Sciences, Bhubaneswar, India, from June to August 2018. Pain severity was evaluated by visual analog scale (VAS) at the time of interview and after 1 week/completion of pain treatment.
RESULTS
The prevalence of pain during the 24 hours preceding the interview was 70.6%. The duration of pain was ≥4 weeks in 162 (27.1%) patients and severe (VAS ≥ 7) in 144 (24.1%) patients. The mean VAS score was 6.27 ± 1.97 at the time of interview and 3.31 ± 1.89 after 1 week/completion of pain treatment (p < .001). Use of opioid analgesics (adjusted odds ratio [aOR]: 3.18; confidence interval [CI]: 2.23-4.55) was significantly related to pain severity, whereas patients ≥60 years (aOR: 1.64; CI: 0.99-2.70), patients in a nonsurgical ward (aOR: 1.78; CI: 1.21-2.60), and patients using opioid analgesics (aOR: 2.63; CI: 1.73-3.98) had prolonged pain, defined as ≥4 weeks.
CONCLUSION
Pain prevalence and intensity in this Indian hospital were high and pain treatment was adequate in many cases. Timely assessment and appropriate management of pain in hospitalized patients is needed to prevent further pain and its complications in these patients.
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10.1016/j.pmn.2019.06.005
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pubmed_134_22039
|
PURPOSE
We report our experience with salvage radical surgery as palliative treatment in patients with bulky recurrence of prostate cancer following radical prostatectomy (RP).
MATERIALS AND METHODS
From files at the department of urology we identified 5 patients who had biopsy confirmed, bulky recurrence of prostate cancer after initial RP and subsequent salvage radiation therapy (4), prior to presentation at our cancer center. Positive surgical margins were present in all 5 patients. All received androgen ablation and 4 also received systemic chemotherapy. Due to persistent bulky tumors in the 5 patients and debilitating unrelenting symptoms, including refractory hematuria, obstructive uropathy and pelvic pain in 4, salvage radical surgery was performed. Total pelvic exenteration was done in 4 patients and wide tumor resection with continent urinary diversion was done in 1.
RESULTS
Four patients were permanently relieved of local symptoms following surgery and another had entero-urethral fistula formation. Revision of a continent urinary diversion was necessary in another patient who was otherwise free of cancer and of local pelvic symptoms. Long-term symptom-free survival was achieved in 2 patients following surgery at 26 and 56 months, respectively. One patient died of metastatic disease 3.5 months after surgery but he had been rendered free of local symptoms by surgery. The other 2 patients are currently free of local symptoms 5 and 7 months following surgery, respectively. Wound infection, delirium and prolonged ileus occurred in 1 patient each. Otherwise surgery was well tolerated.
CONCLUSIONS
Salvage radical surgery is feasible and it provides effective palliation in patients with bulky local recurrence following RP.
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10.1097/01.ju.0000152394.32858.14
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pubmed_355_20963
|
The structure of beta-amyloid (beta A) from Alzheimer disease brains was examined to determine if post-translational modifications might be linked to the abnormal deposition of this peptide in the diseased tissue. The beta A peptides were isolated from the compact amyloid cores of neuritic plaques and separated from minor glycoprotein components by size-exclusion high-pressure liquid chromatography (HPLC). This parenchymal beta A has a maximal length of 42 residues, but shorter forms with "ragged" NH2 termini are also present. Tryptic peptide analysis revealed heterogeneity in the beta A1-5 and beta A6-16 peptides, each of which eluted as four peaks on reverse phase HPLC. Amino acid composition and sequence analyses, mass spectrometry, enzymatic methylation, and stereoisomer determinations revealed that these multiple peptide forms resulted from structural rearrangements of the aspartyl residues at beta A positions 1 and 7. The L-isoaspartyl form predominates at each of these positions, whereas the D-isoaspartyl, L-aspartyl, and D-aspartyl forms are present in lesser amounts. beta A purified from the leptomeningeal microvasculature contains the same structural alterations as parenchymal beta A, but is 2 residues shorter at its COOH terminus. Using two different purification protocols, and using a synthetic beta A1-42 peptide as a control, we show that these modifications arose endogenously and were not caused by the experimental manipulations. The abundance of structurally altered aspartyl residues may profoundly affect the conformation of the beta A protein within plaque cores and thus significantly impact normal catabolic processes designed to limit its deposition. These alterations may therefore contribute to the production and stability of beta-amyloid deposits in Alzheimer brain tissue.
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pubmed_355_20963
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pubmed_832_15585
|
SUMMARY
We describe a 56-year-old postmenopausal woman with hypertension, hypokalemia and severe alopecia who was found to have a 4.5-cm lipid-poor left adrenal mass on CT scan performed to evaluate her chronic right-sided abdominal pain. Hormonal studies revealed unequivocal evidence of primary aldosteronism and subclinical hypercortisolemia of adrenal origin. Although a laparoscopic left adrenalectomy rendered her normotensive, normokalemic and adrenal insufficient for 2.5 years, her alopecia did not improve and she later presented with facial hyperpigmentation acne, worsening hirsutism, clitoromegaly, and an estrogen receptor-positive breast cancer. Further testing demonstrated markedly elevated serum androstenedione and total and free testosterone and persistently undetectable DHEAS levels. As biochemical and radiologic studies ruled out primary adrenal malignancy and obvious ovarian neoplasms, a bilateral salpingo-oophorectomy was undertaken, which revealed bilateral ovarian hyperthecosis. This case highlights how the clinical manifestations associated with hyperaldosteronism and hypercortisolemia masqueraded the hyperandrogenic findings. It was only when her severe alopecia failed to improve after the resolution of hypercortisolism, hyperandrogenic manifestations worsened despite adrenal insufficiency and an estrogen receptor-positive breast cancer was found, did it becomes apparent that her symptoms were due to ovarian hyperthecosis.
LEARNING POINTS
As cortisol cosecretion appears to be highly prevalent in patients with primary aldosteronism, the term 'Connshing' syndrome has been suggested. The associated subclinical hypercortisolemia could be the driver for the increased metabolic alterations seen in patients with Conn syndrome. The identification of these dual secretors before adrenal venous sampling could alert the clinician about possible equivocal test results. The identification of these dual secretors before unilateral adrenalectomy could avoid unexpected postoperative adrenal crises. Hyperfunctioning adrenal and ovarian lesions can coexist, and the clinical manifestations associated with hypercortisolemia can masquerade the hyperandrogenic findings.
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pubmed_832_15585
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pubmed_143_2900
|
Care and research in childhood cerebral palsy (CP) continue to evolve. As our understanding of CP grows more nuanced, so grows our need to describe function, activities, challenges, adaptations of children with CP. In CP, robust means of measuring outcomes are vital to understanding utility of treatments. Research must accurately measure meaningful constructs of children with CP as a reliable ruler to establish if interventions produce useful effects. This article addresses the challenges of outcome measurement in CP, current status of outcome measurement in CP, and issues of understanding change in childhood CP.
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10.1016/j.pmr.2019.09.011
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pubmed_415_5096
|
Neuromyelitis optica (NMO) is associated with antibodies to aquaporin-4 (termed NMO-IgG or AQP4-Ab) in 60-90% of cases. Little is known about the aetiology of NMO in NMO-IgG/AQP4-Ab negative patients. Here we report on CV2/CRMP5 antibodies in a 69-year-old male patient with NMO-IgG/AQP4-Ab negative NMO. The association of CV2/CRMP5-Ab with prostate cancer suggests a paraneoplastic aetiology of NMO in our patient. Our report strengthens the case of antibodies other than AQP4-Ab being involved in the immunopathogenesis in a subset of patients with NMO. We conclude that CV2/CRMP5-Ab should be included in the differential diagnosis of NMO, in particular if AQP4-Ab are negative and irrespective of whether a tumour is known or not. We recommend that recombinant tests, which are increasingly used because of their higher sensitivity and specificity, should always be accompanied by standard indirect immunofluorescence employing brain tissue sections in order to avoid CV2/CRMP5-Ab or other paraneoplastic antibodies being overlooked. In addition, we provide a comprehensive review of all patients with CV2/CRMP5-Ab and NMO-like disease published in the English literature so far.
|
10.1016/j.clineuro.2011.10.048
|
pubmed_105_14117
|
Background
Central nervous system tumors are now the most common primary neoplasms seen in children, and radiation therapy is a key component in management. Secondary malignant neoplasms (SMNs) are rare, but dreaded complications. Proton beam therapy (PBT) can potentially minimize the risk of SMNs compared to conventional photon radiation therapy (RT), and multiple recent studies with mature data have reported the risk of SMNs after PBT. We performed this systematic review and meta-analysis to characterize and compare the incidence of SMNs after proton and photon-based radiation for pediatric CNS tumors.
Methods
A systematic search of literature on electronic (PubMed, Cochrane Central, and Embase) databases was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. We included studies reporting the incidence and nature of SMNs in pediatric patients with primary CNS tumors. The crude incidence of SMNs and all secondary neoplasms were separately extracted, and the random-effects model was used for pooled analysis and subgroup comparison was performed between studies using photons vs. protons.
Results
Twenty-four studies were included for analysis. A total of 418 SMNs were seen in 38,163 patients. The most common SMN were gliomas (40.6%) followed by meningiomas (38.7%), sarcomas (4.8%), and thyroid cancers (4.2%). The median follow-up was 8.8 years [3.3-23.2].The median latency to SMN for photons and protons were 11.9 years [5-23] and 5.9 years [5-6.7], respectively. The pooled incidence of SMNs was 1.8% (95% CI: 1.1%-2.6%, I2 = 94%) with photons and 1.5% (95% CI: 0%-4.5%, I2 = 81%) with protons. The pooled incidence of all SNs was not different [photons: 3.6% (95% CI: 2.5%-4.8%, I2 = 96%) vs. protons: 1.5% (95% CI: 0-4.5%, I2 = 80%); p = 0.21].
Conclusion
We observed similar rates of SMN with PBT at 1.5% compared to 1.8% with photon-based RT for pediatric CNS tumors. We observed a shorter latency to SMN with PBT compared to RT. With increasing use of pencil beam scanning PBT and VMAT, further studies are warranted to evaluate the risk of secondary cancers in patients treated with these newer modalities.
|
10.3389/fonc.2022.893855
|
pubmed_18_3007
|
INTRODUCTION
Acute cellular rejection is a major cause of graft loss in heart transplantation (HT). Endomyocardial biopsy remains the gold standard for its diagnosis, but it is an invasive procedure not without risk. A proinflammatory state exists in rejection that could be assessed by determining plasma levels of inflammatory biomarkers.
OBJECTIVE
To analyze the utility of various inflammatory markers, which is most important and what values best classify patients to diagnose rejection.
MATERIALS AND METHODS
A prospective study in 123 consecutive cardiac transplant recipients was conducted from January 2002 to December 2006. Fibrinogen protein (Fgp) and function (Fgf), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and sialic acid (SA) determinations were performed at one, two, four, six, nine, and 12 months post-HT at the same time as biopsies. Coronary arteriography and intravascular ultrasound were performed on the first and last follow-up visits. Heart-lung transplants, retransplants, pediatric transplants, patients who died in the first month, and patients who refused consent were excluded. Also excluded were determinations that coincided with renal dysfunction, active infection, hemodynamic instability, or a non-evaluable biopsy. The final analysis included 79 patients and 294 determinations. The correlation between the levels of these biomarkers and the presence of rejection in the biopsy (> or = ISHLT grade 3) was studied.
RESULTS
We did not find significant differences in the values of any of the markers analyzed on the six follow-up visits. Only CRP showed significant and sustained differences between the two groups (with and without rejection) from the second follow-up visit (month 2). The area under the curve showed significant differences in Fgp (0.614, p = 0.013), Fgf (0.585, p = 0.05), TNF-alpha (0.605, p = 0.02), SA (0.637, p = 0.002) and mainly CRP (0.765, p = 0.0001). CRP levels below 0.87 mg/dL ruled out rejection with a specificity of 90%.
CONCLUSIONS
Among the inflammatory markers analyzed, CRP was the most useful parameter for non-invasive screening of acute cellular rejection in the first year post-HT.
|
10.1111/j.1399-0012.2009.01074.x
|
pubmed_868_1145
|
AIMS
To investigate cross-sectional and longitudinal associations between personality and smoking, and test whether socio-demographic factors modify these associations.
DESIGN
Cross-sectional and longitudinal individual-participant meta-analysis.
SETTING
Nine cohort studies from Australia, Germany, the United Kingdom and the United States.
PARTICIPANTS
A total of 79 757 men and women (mean age = 50.8 years).
MEASUREMENTS
Personality traits of the five-factor model (extraversion, neuroticism, agreeableness, conscientiousness and openness to experience) were used as exposures. Outcomes were current smoking status (current smoker, ex-smoker and never smoker), smoking initiation, smoking relapse and smoking cessation. Associations between personality and smoking were modelled using logistic and multinomial logistic regression, and study-specific findings were combined using random-effect meta-analysis.
FINDINGS
Current smoking was associated with higher extraversion [odds ratio per 1 standard deviation increase in the score: 1.16; 95% confidence interval (CI) = 1.08-1.24], higher neuroticism (1.19; 95% CI = 1.13-1.26) and lower conscientiousness (95% CI = 0.88; 0.83-0.94). Among non-smokers, smoking initiation during the follow-up period was predicted prospectively by higher extraversion (1.22; 95% CI = 1.04-1.43) and lower conscientiousness (0.80; 95% CI = 0.68-0.93), whereas higher neuroticism (1.16; 95% CI = 1.04-1.30) predicted smoking relapse among ex-smokers. Among smokers, smoking cessation was negatively associated with neuroticism (0.91; 95% CI = 0.87-0.96). Socio-demographic variables did not appear to modify the associations between personality and smoking.
CONCLUSIONS
Adult smokers have higher extraversion, higher neuroticism and lower conscientiousness personality scores than non-smokers. Initiation into smoking is associated positively with higher extraversion and lower conscientiousness, while relapse to smoking among ex-smokers is associated with higher neuroticism.
|
10.1111/add.13079
|
pubmed_837_16095
|
An Epstein-Barr virus (EBV) genome-positive epithelial hybrid cell line, NPC-KT, derived from the fusion of primary nasopharyngeal carcinoma cells with a human epithelial cell line of adenoid origin has previously been described (Takimoto, Kamide, and Umeda, 1984a; Takimoto, Ogura, Sato, and Hatano, 1984b; Takimoto, Ogura, Sato, Umeda, and Hatano, 1985). The NPC-KT cells produce virus (NPC virus) with both transforming and lytic properties. An EBV genome-negative human lymphoblastoid cell line, Ramos, was infected with NPC virus. Three months after infection, more than 90% of the cell population expressed EBV-associated nuclear antigen (EBNA). Approximately 40% of the cells exhibited a brilliant pattern, whereas the remaining 50% of the cells showed a faint granular pattern. The result suggests that there may be heterogeneity in NPC virus.
|
10.1016/s0385-8146(87)80025-1
|
pubmed_748_17453
|
We present specific heat measurements on Pr(2-x)CexCuO(4-delta) single crystals which show an unexpected change in the field dependence of the electronic specific heat (Cel) from linear at T = 2 K to nonlinear at T > or = 3 K. We consider several possible explanations for this change and propose, as a possible interpretation, a phase transition in the symmetry of the order parameter from nodal (e.g., d wave) at T > or = 3 K to gapped (e.g., s wave) at T = 2 K. Such a phase transition could be an explanation for the previous conflicting experimental results on the pairing symmetry in the electron-doped cuprates.
|
10.1103/PhysRevLett.93.067001
|
pubmed_727_10858
|
The influence of intravenous infusions of various concentrations of NaCl solutions on temperature regulation was investigated in dogs at rest and during moderate exercise for 1 h on a treadmill. Infusion of hypertonic solutions either before and during exercise resulted in elevated (P less than 0.05) plasma Na+ and osmotic concentrations and produced higher equilibrium levels (P less than 0.05) of rectal temperature (Tre) during exercise (prehypertonic 40.9 degrees C vs. no infusion 40.4 degrees C; hypertonic 40.8 degrees C vs. isotonic infusion 40.4 degrees C), but not at rest. Increasing the [Na+] and osmotic concentrations above 170 meq/liter and 325 mosmol/kg, respectively, resulted in no additional increase in exercise Tre. Water consumption during exercise decreased (P less than 0.05) plasma [Na+], osmolality, and the equilibrium level of Tre to control levels. There was no effect of changes in plasma volume (PV) of +/- 8% on the time course, equilibrium level, or change in Tre during exercise. At the end of exercise, there were moderate correlations (P less than 0.01) between Tre and [Na+] (r = 0.51) and Tre and osmoti (r = 0.52) concentrations. It was concluded that a) the exercise Tre responses of the dog respond quantitatively like man to elevated plasma [Na+] and osmolality, b) the Tre levels are not influenced by changes in PV, and c) water intake significantly reduces the ion-osmotic hyperthermia.
|
10.1152/ajplegacy.1976.230.1.74
|
pubmed_996_18055
|
Excitatory amino acid (EAA) and cholinergic neurotransmission in the spinal cord of urethan-anesthetized rats was investigated to assess mechanisms regulating sympathetic activity after spinal cord injury. Blockade of EAA transmission by intrathecal injection of kynurenic acid decreased arterial blood pressure by 24 +/- 4 mmHg, heart rate by 15 +/- 10 beats/min, and renal sympathetic nerve activity (RSNA) by 85 +/- 4% in intact rats. In rats with cervical spinal transections, this blockade decreased RSNA by 51 +/- 5% and had no effect on arterial pressure and heart rate. Muscarinic blockade by intrathecal atropine decreased RSNA by 12 +/- 3 and 32 +/- 6% in intact and spinal rats, respectively, and caused no cardiovascular responses in either group. Combined blockade of EAA and muscarinic receptors in spinal rats decreased RSNA by 77 +/- 1%. Intrathecal injections of the EAA agonist D,L-homocysteic acid in spinal rats caused initial increases (335 +/- 28%) in RSNA lasting approximately 3 min and later sustained increases (157 +/- 19%) lasting 36 +/- 8 min. Only the early excitation increased arterial pressure by 17 +/- 3 mmHg, and then pressure returned to baseline values. The EAA agonist kainic acid increased RSNA by 402 +/- 90% in spinal rats, an effect lasting 70 +/- 5 min, and increased arterial pressure by only 8 +/- 2 mmHg for 12 +/- 5 min. These findings suggest that tonic activity of spinal neurons with EAA and cholinergic receptors maintains tonic RSNA after spinal cord transection. However, this activity does not play a major role in maintaining arterial pressure, even if it is increased substantially by EAA receptor stimulation.
|
10.1152/ajpheart.1994.266.4.H1485
|
pubmed_751_14012
|
A study was undertaken to determine the changes in the seminal fluid of adult patients presenting with unilateral testicular torsion. There was beneficial effect from excising an infarcted torsive testis and a deleterious effect from retaining it.
|
10.1016/0090-4295(86)90365-1
|
pubmed_526_4487
|
OBJECTIVES
To assess whether a true knowledge of crowding alters treatment decisions compared with estimates of crowding.
MATERIALS AND METHODS
Thirty-six orthodontists were asked to estimate crowding using visualization on eight mandibular arch study models and to indicate possible extraction choices. For each model, the intermolar widths, intercanine widths, and clinical scenarios were identical, but the true crowding varied from 0.2 to 8.4mm as to a lesser extent did the curve of Spee. Eleven orthodontists repeated the visualization exercise after 2 weeks to assess reliability. All 36 of the orthodontists were asked to repeat the treatment planning exercise on the same models, but this time was provided with the true amount of crowding in each case.
RESULTS
When the 36 orthodontists used direct visualization of the models to assess crowding, the range of their estimates of crowding increased as the crowding increased. As might be expected, they also tended to move towards extraction treatments as the crowding increased (P = 0.013, odds ratio = 3). Although the reliability of the repeat estimates of crowding were moderate, the mean estimates were greater than the true crowding for each model. When orthodontists were presented with the true amount of crowding, rather than their estimate of crowding, it had a significant effect on the decision to extract, with fewer orthodontists recommending extractions.
LIMITATIONS
The principal limitation of this study is that it was a laboratory-based study and utilized just the mandibular arch model for estimation and treatment planning.
CONCLUSIONS
Direct visualization may overestimate the amount of crowding present. When the true amount of crowding is known, it can lead to more consistent treatment planning, with the decision to extract fewer teeth in the borderline cases. A formal space analysis is likely to assist with treatment planning.
|
10.1093/ejo/cjv011
|
pubmed_335_24769
|
BACKGROUND
Acinetobacter baumannii has become an increasingly important nosocomial pathogen. Carbapenem is the preferred drug of choice for treatment of multidrug-resistant gram-negative bacilli, but carbapenem-resistant A baumannii (CRAB) has now emerged. The aim of this study was to determine the incidence, outcomes, and risk factors for CRAB bacteremia in liver transplant recipients.
METHODS
The medical records of 393 subjects who underwent living donor liver transplant at Seoul St. Mary's Hospital from January 2008 to April 2015 were reviewed.
RESULTS
A total of 92 (23.4%) bacteremic patients, comprising 156 episodes, were identified. Fourteen patients, totaling 18 episodes, had CRAB bacteremia. The median time of emergence of CRAB bacteremia was 55.5 (range, 2-829) days after transplantation, and 72.2% of episodes (n = 13) occurred within 6 months of transplant. The presumed sources of infection were intra-abdominal (n = 11, 61.1%), biliary tract (n = 3, 16.7%), lung (n = 2, 11.1%), catheter (n = 1, 5.6%), and wound (n = 1, 5.6%). By multivariate analysis, length of post-transplant intensive care unit (ICU) stay (odds ratio [OR], 1.1, 95% confidence interval [CI], 1.11-1.15; P = .04) was associated with CRAB bacteremia. Overall mortality in 14 recipients with CRAB bacteremia was 50% (n = 7), but only 10% (30 of 301) in non-bacteremic patients and 20.5% (16 of 78) in other bacteremic patients excluding CRAB (P < .001).
CONCLUSION
In our study, patients with CRAB bacteremia after liver transplant showed an unfavorable outcome and, recently, CRAB has become an increasingly major pathogen at our center. Reducing the length of ICU stay could be a solution for preventing CRAB bacteremia.
|
10.1016/j.transproceed.2018.01.043
|
pubmed_796_4585
|
We measured the binding of [3H]-5-(N-methyl-N-isobutyl) amiloride (MIA) to purified rabbit renal brush border membranes. MIA binding was protein, temperature and time dependent with optimal binding at pH 8.0 or above. At low pH MIA binding was inhibited, suggesting competition between H+ ions and MIA for the MIA binding site. There was 70-80% specific binding which reached a plateau at 30 min and remained stable thereafter for 150 min. Scatchard analysis revealed one family of binding sites with Bmax of 3.4 +/- 0.4 pmoles/mg protein and Kd of 30.5 +/- 2.3 nM. MIA inhibited the Vmax of the Na-H antiporter (assessed by acridine orange quenching) in a dose dependent fashion with 100% inhibition at MIA concentration of 10(-3) M and this inhibition was greater than that of amiloride. We conclude that MIA, a potent inhibitor of the Na-H antiporter, displays a high percentage of specific binding to renal brush border membranes and can be used to assess the number of the Na-H antiporters.
|
10.1016/0024-3205(89)90102-1
|
pubmed_935_14364
|
The possible embryogenesis of diplomyelia is discussed in the context of the current understanding of neurulation. The mechanisms of normal development of the neural tube differ from one region to another, so the initial step in development of diplomyelia will probably depend on the location of the lesion. In the cranial portion of the neural tube, abnormal folding of the neural plate is most likely to be responsible for the formation of supernumerary lumina. In the intermediate transitional region, the neural plate diminishes as the contribution from the end bud increases, so errors might originate in either or both of these structures. In the caudal region of the embryo, the neural tube is established by canalization of the solid medullary cord, so diplomyelia in this region is most likely to stem from faulty canalization. Once the sub-populations of neural cells have been established, their subsequent physical separation appears to be due to changes in the region between the adjacent lumina, for example enlargement of intercellular spaces and degeneration of neural cells.
|
10.1111/j.1469-8749.1980.tb04334.x
|
pubmed_548_19123
|
Numerous mechanisms have been postulated to play an important role in the pathogenesis of poikiloderma of Civatte (PC), including chronic exposure to ultraviolet radiation, menopause-related hormonal changes, contact hypersensitivity and genetic predisposition. Herein, we report a case of contact sensitization to fragrances and commonly used preservatives, methylchloroisothiazolinone and methylisothiazolinone, also widely known as Kathon CG, in a post-menopausal woman with PC, who denied excessive sun exposure and a family history. After abstaining from the use of her personal care products containing the documented allergens, not only the itching and burning symptoms, but also the cutaneous changes appeared to improve partially. This report underlines the possible influence of contact hypersensitivity in the pathogenesis of PC.
|
10.1159/000369489
|
pubmed_495_12636
|
The standard ELISA for measuring rheumatoid factor (RF) binding was modified by treatment after the RF-Fc interaction with 2 M guanidine, which allowed a measurement of the avidity of the interaction. Incubation with 4 M guanidine eliminated RF binding. There was a direct correlation (r = 0.99) between the avidity as measured by the modified guanidine ELISA, and the dissociation constant for monoclonal RFs, as measured by competitive ELISA. Of the seropositive rheumatoid arthritis (RA) patients tested, 47% had high-avidity RFs (> or = 8% RF binding remaining after guanidine treatment). Tender joint count scores were significantly higher in the high avidity group (p = 0.05), whereas there was no significant difference in the ages, disease duration, sedimentation rate, RF titer or serum Ig levels compared to those with low-avidity RFs. Additionally 58% of those with high-avidity RFs had subcutaneous nodules, compared to 40% of the low-avidity group. A significantly higher number of nodules was present in the high-avidity RF group compared to those with low-avidity RFs (p = 0.03). Interestingly, the RF avidity was significantly higher in isolated immune complexes (IC), compared to that in circulating IgM RFs (p = 0.01). The RF avidity correlated with the presence of the glycoform of IgG lacking galactose in both circulating and IC-derived IgG (p = 0.003 and 0.009 respectively). Information about the strength of binding to Fc identifies a subgroup of IgM RFs that are likely pathological in patients with RA, as well as a specific glycoform of the target antigen.
|
10.1007/BF01540882
|
pubmed_224_8519
|
Rickets, whether due to lack of proper nutrition or secondary to disease or medication, may be unexpectedly detected on radiographs obtained for other reasons. Several recent examples are reported here. It is important to be aware of the manifestations of rickets so that appropriate treatment is not delayed. Physicians should be alert for signs of rickets in the x-ray examination of any child.
|
pubmed_224_8519
|
pubmed_380_17432
|
BACKGROUND
Pilomatricomas, which are usually solitary, firm to hard tumors that are covered by normal skin, rarely show a bullous appearance.
OBJECTIVE
To discuss, through a case report, the clinical and histopathologic characteristics of bullous pilomatricomas.
METHODS
A 15-year-old boy presented with a firm, well-defined tumor on his right arm that showed dark-blue discoloration and bullous formation over it.
RESULTS
Excisional biopsy was performed, and histopathologic examination confirmed the diagnosis of bullous pilomatricoma.
CONCLUSION
The presence of dilated lymphatics, also seen in our patient, is a common feature of bullous pilomatricomas.
|
10.1046/j.1524-4725.2003.29304.x
|
pubmed_954_3903
|
Levels of IL-18 were significantly lower in women with recurrent miscarriage (RM) than those without idiopathic RM. IL-18 promoter single nucleotide polymorphisms were previously identified to have an impact on IL18 gene transcription activity and influence the level of IL-18 protein production. The aim of this study was to evaluate whether IL-18 gene polymorphisms are risk factors for idiopathic RM in Chinese Han population. Study subjects comprised of 484 idiopathic RM patients and 468 controls. Three polymorphisms (rs360717, rs187238, rs1946518) in IL-18 gene and serum IL-18 concentrations were assessed. rs187238 variant exhibits significant association with RM in additive and recessive genetic model (additive model p = 1.05 × 10(-4), dominant model p = 0.025, recessive model p = 2.43 × 10(-5)). In contrast, rs360717 and rs1946518 are not significantly associated with RM. Serum IL-18 levels are significantly lower in RM cases than in control (111.98 ± 93.13 versus 148.74 ± 130.51 pg/mL, p = 7.42 × 10(-7)). There are lower levels of serum IL-18 in rs187238 homozygous mutant (CC) than homozygous wild-type (GG) in this study population, including cases and control groups (98.31 ± 86.46 versus 131.87 ± 115.02 pg/mL, p = 0.015). These results suggest that reduced IL-18 levels and rs187238 variant may contribute to pathogenesis of idiopathic RM in Chinese Han population.
|
10.3390/ijms16024180
|
pubmed_781_15589
|
AIM
To provide insight into potential regulatory mechanisms of gene expression underlying addiction, analgesia, psychotropic drug response and adverse drug events, genome-wide association studies searching for variants associated with these phenotypes has been undertaken with limited success. We undertook analysis of these results with the aim of applying epigenetic knowledge to aid variant discovery and interpretation.
METHODS
We applied conditional imputation to results from 26 genome-wide association studies and three candidate gene-association studies. The analysis workflow included data from chromatin conformation capture, chromatin state annotation, DNase I hypersensitivity, hypomethylation, anatomical localization and biochronicity. We also made use of chromatin state data from the epigenome roadmap, transcription factor-binding data, spatial maps from published Hi-C datasets and 'guilt by association' methods.
RESULTS
We identified 31 pharmacoepigenomic SNPs from a total of 2024 variants in linkage disequilibrium with lead SNPs, of which only 6% were coding variants. Interrogation of chromatin state using our workflow and the epigenome roadmap showed agreement on 34 of 35 tissue assignments to regulatory elements including enhancers and promoters. Loop boundary domains were inferred by association with CTCF (CCCTC-binding factor) and cohesin, suggesting proximity to topologically associating domain boundaries and enhancer clusters. Spatial interactions between enhancer-promoter pairs detected both known and previously unknown mechanisms. Addiction and analgesia SNPs were common in relevant populations and exhibited large effect sizes, whereas a SNP located in the promoter of the SLC1A2 gene exhibited a moderate effect size for lithium response in bipolar disorder in patients of European ancestry. SNPs associated with drug-induced organ injury were rare but exhibited the largest effect sizes, consistent with the published literature.
CONCLUSION
This work demonstrates that an in silico bioinformatics-based approach using integrative analysis of a diversity of molecular and morphological data types can discover pharmacoepigenomic variants that are suitable candidates for further validation in cell lines, animal models and human clinical trials.
|
10.2217/pgs.15.105
|
pubmed_311_25247
|
CRISPR-Cas9-based combinatorial perturbation approaches for orthogonal knockout and gene activation have been impeded by complex vector designs and co-delivery of multiple constructs. Here, we demonstrate that catalytically active CRISPR-Cas12a fused to a transcriptional-activator domain enables flexible switching between genome editing and transcriptional activation by altering guide length. By leveraging Cas12a-mediated CRISPR-RNA array processing, we illustrate that Cas12a-VPR enables simplified multiplexed knockout and transcriptional activation in vitro and in vivo.
|
10.1038/s41592-018-0262-1
|
pubmed_635_5707
|
Ribavirin is a nucleoside which is used as an antiviral agent against both RNA and DNA viruses. However, accumulation in erythrocytes causes hemolysis which limits its usefulness. To minimize ribavirin-induced hemolysis and increase its antiviral effect, considerable efforts have been made involving chemical prodrugs and various formulations. Combination with macromolecules to achieve better targeting and increased uptake is one of the most promising strategies. In addition, decreasing the association with RBCs through prodrugs and delivery systems is considered. This review summarizes prodrugs and delivery systems for ribavirin and, at the same time examines these different strategies. Moreover, a novel design of prodrug is proposed for further study.
|
pubmed_635_5707
|
pubmed_143_18988
|
Alzheimer disease (AD) is a neurodegenerative disease characterized by deposition of pathologically aggregated amyloid-β in the extracellular space and pathologically aggregated tau protein in the intracellular space. Mainly affected brain areas are the temporal and the parietal lobe, which cause the classical AD phenotype consisting of increasing forgetfulness and difficulties to orientate. However, AD pathology is not restricted to these brain areas and spreads through the brain as the disease progresses, which can lead to a number of additional symptoms and to atypical presentations. Motor symptoms in AD are the topic of this chapter. Even though motor symptoms are usually not severe and seldomly treated, motor symptoms are quite frequent and can be observed in the majority of AD cases. Motor symptoms are especially frequent in cases with early onset and long disease duration, for example in Apolipoprotein E e4 carriers and in familial early onset AD. In severe cases treatment with pharmacological approaches might be considered. However, treatment strategies largely rely on expert opinions. Due to potential positive impact on prognosis non-pharmacological treatment and exercise might be considered in less advanced cases.
|
10.1016/bs.irn.2019.10.005
|
pubmed_333_371
|
Sarcoid patients frequently show depression of skin delayed hypersensitivity reactions suggesting depression of thymic (T) lymphocyte function. In vitro demonstration of such depression, however, to date, is inconclusive. We have used the macrophage migration inhibition test with Kveim "antigen" (KMIF), and spontaneous sheep red cell rosetting (SRC) techniques as indicator systems. We found that a positive KMIF test obtained in 7 of 16 subjects (13 sarcoid and 3 non sarcoid) in the presence of foetal bovine sera (FBS) became negative in the presence of sarcoid patients sera. Using lymphocytes from a single normal healthy subject the SRC tests were performed in the presence of sarcoid, normal healthy sera and FBS. With sarcoid sera 38% of lymphocytes showed rosetting as compared with normal human sera, 54%, and with FBS, 57%. Where lymphocytes were pre-incubated for one hour in the various sera the percentage of rosetting cells were even further reduced, sarcoid sera 23%, as compared to normal human sera, (49%), and FBS, (54%). Thus, using two tests of lymphocyte function our preliminary results suggest the presence of T cell inhibitory factors in sarcoid sera.
|
pubmed_333_371
|
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