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pubmed_905_15157 | We consider the insertion of alkali-halide ion pairs into a narrow (5,5) carbon nanotube. In all cases considered, the insertion of a dimer is only slightly exothermic. While the image charge induced on the surface of the tube favors insertion, it simultaneously weakens the Coulomb attraction between the two ions. In addition, the anion experiences a sizable Pauli repulsion. For a one dimensional chain of NaCl embedded in the tube the most favorable position for the anion is at the center, and for the cation near the wall. The phonon spectrum of such chains shows both an acoustic and an optical branch. | 10.1039/c6fd00076b |
pubmed_98_13207 | In this work, we set out to better understand how the permeation enhancer sodium caprate (C10) influences the intestinal absorption of macromolecules. FITC-dextran 4000 (FD4) was selected as a model compound and formulated with 50-300 mM C10. Absorption was studied after bolus instillation of liquid formulation to the duodenum of anesthetized rats and intravenously as a reference, whereafter plasma samples were taken and analyzed for FD4 content. It was found that the AUC and Cmax of FD4 increased with increasing C10 concentration. Higher C10 concentrations were associated with an increased and extended absorption but also increased epithelial damage. Depending on the C10 concentration, the intestinal epithelium showed significant recovery already at 60-120 min after administration. At the highest studied C10 concentrations (100 and 300 mM), the absorption of FD4 was not affected by the colloidal structures of C10, with similar absorption obtained when C10 was administered as micelles (pH 8.5) and as vesicles (pH 6.5). In contrast, the FD4 absorption was lower when C10 was administered at 50 mM formulated as micelles as compared to vesicles. Intestinal dilution of C10 and FD4 revealed a trend of decreasing FD4 absorption with increasing intestinal dilution. However, the effect was smaller than that of altering the total administered C10 dose. Absorption was similar when the formulations were prepared in simulated intestinal fluids containing mixed micelles of bile salts and phospholipids and in simple buffer solution. The findings in this study suggest that in order to optimally enhance the absorption of macromolecules, high (≥100 mM) initial intestinal C10 concentrations are likely needed and that both the concentration and total dose of C10 are important parameters. | 10.1021/acs.molpharmaceut.1c00724 |
pubmed_414_21560 | INTRODUCTION
Genetic associations of American sarcoidosis susceptibility implicate MHC class II allele, DRB1*1101. We previously reported immune recognition of Mycobacterium peptides from peripheral cells of 26 sarcoidosis subjects, 24 PPD- healthy volunteers, and eight with latent tuberculosis infection.
MATERIALS AND METHODS
In order to further link these genetic and immunologic pillars of sarcoidosis pathogenesis, we performed flow cytometry on these same subjects to identify the cells responsible for immune responses to ESAT-6 and katG peptides, followed by HLA typing to determine allelic associations with recognition.
DISCUSSION AND CONCLUSION
Sarcoidosis CD4+ T cells were primarily responsible for the systemic responses. Recognition was inhibited by monoclonal antibody against HLA-DR and HLA-DQ, but not HLA-DP. Immune recognition of ESAT-6 peptide NNALQNLARTISEAG was associated with possession of DRB1*1101. ESAT-6 and katG presented by antigen-presenting cells expressing DRB1*1101-induced Th-1 responses from sarcoidosis T cells, thus providing a mechanistic insight for the association of HLA DRB1*1101 with sarcoidosis, and sarcoidosis T cell interaction with microbial antigens. | 10.1007/s10875-009-9311-y |
pubmed_54_13484 | This research presents an examination of Black gay men and their lived experiences while undergraduates at historically Black colleges and universities (HBCUs). Based on 10 in-depth interviews with self-identified Black gay men, the author presents four emergent themes, which reveal the complex ways in which Black gay men navigate and negotiate the intersections of their multiple identities as related to race, sexual orientation, and gender at HBCUs. The findings of this research have implications for larger discussions of community, Black masculinity, and gay identity in predominantly Black and non-Black contexts. | 10.1080/00918369.2014.972814 |
pubmed_643_20327 | INTRODUCTION
In theory, the direct anterior approach offers the only path to performing minimally invasive total hip arthroplasty in an intermuscular, internervous plane.
STEP 1 POSITION AND DRAPE PATIENT
Careful positioning is necessary to complete this procedure on a standard operating room table.
STEP 2 SUPERFICIAL EXPOSURE
Incise the fascia overlying the tensor fasciae latae and lift up the anterior edge, avoiding the perforating vessels.
STEP 3 DEEP EXPOSURE
The hip is flexed 30° during the deep dissection.
STEP 4 PREPARE ACETABULUM AND IMPLANT ACETABULAR COMPONENT
Ream the acetabulum in 10° to 15° of anteversion with an abduction angle of 40° to 45°.
STEP 5 PREPARE FEMUR AND IMPLANT FEMORAL COMPONENT
Use offset broaches to access the femur and prevent perforation through the greater trochanter.
STEP 6 TRIAL AND CLOSE
Specifically check for impingement of bone on the implant with the hip flexed 90°.
RESULTS
This approach has been used successfully for total hip arthroplasty for decades.
WHAT TO WATCH FOR
IndicationsContraindicationsPitfalls & Challenges. | 10.2106/JBJS.ST.K.00015 |
pubmed_323_22517 | There are two arylhydrocarbon receptor (AhR) isoforms in birds, AhR1 and AhR2. The varying sensitivity of AhR is reported to be related to two critical amino acids at positions 325 and 381 in the AhR1 ligand-binding domain. In this study, seven avian species whose in vivo dioxin sensitivity was known, and 13 species with no data regarding their in vivo dioxin sensitivity were examined. The two critical amino acids in the ligand-binding domain were investigated in avian species, and the results were compared with the taxonomy or phylogenetic trees for the bird AhR proteins. We found that the two critical amino acids did not correlate with the taxonomy or phylogeny of these proteins, suggesting that dioxin sensitivity was independent of taxonomy. | 10.1292/jvms.13-0179 |
pubmed_742_16822 | In the present work, we prepared core-corona-type nanospheres bearing a thermoresponsive polymer with a controlled chain length on their surface. The corona layers were composed of poly(N-isopropylacrylamide) (PNIPAAm) chains (Mn = 3000-18,000) with a narrow polydispersity index prepared by atom-transfer radical polymerization (ATRP). Nanospheres were prepared by dispersion copolymerization of styrene with the PNIPAAm macromonomer in a polar solvent. The obtained nanospheres were monodisperse in diameter. The diameter of the nanospheres was regulated either by the number or chain length of the PNIPAAm macromonomers. In fact, the nanosphere diameter was regulated from ca. 100 to 1000 nm. When two types of PNIPAAm macromonomers are used, the obtained nanospheres have two different kinds of PNIPAAm on their surface. The surface of the nanospheres was observed to be thermoresponsive nanosphere in 0, 50, 100 mmol L(-1) NaCl aqueous solution. The nanosphere diameter and the surface-grafted polymer were concurrently adjusted for use in biomedical applications. | 10.1021/la4034468 |
pubmed_983_18324 | OBJECTIVE
To evaluate the agreement between de ECG leads with ST elevation and the myocardial segments that present myocardial edema in the MRI study, in patients with acute myocardial infarction.
METHODS
There were included 91 patients with a first ST elevation myocardial infarction (STEMI) with reperfusion therapy during the first 12 hours of onset symptoms, in whom a Cardiovascular Magnetic Resonance (CMR) was done (mean 3 day after the ischemic event). Among the ECG leads (thoracic circle), there were identified those with ST higher elevation. In the CMR there were evaluated the myocardial segments with edema (T2-weighted sequence with hyperintensity).
RESULTS
The ECG leads with the best sensibility in the detection of injury, corresponding to cellular edema, were: basal anterior and anteroseptal: V2; basal inferoseptal LIII and aVF; basal inferior and inferolateral: LIII; basal anterolateral V7-V9; mid anterior and anteroseptal:V2 and V3; mid inferoseptal, inferior and inferolateral: LIII and aVF; mid anterolateral V2 and V8; apical anterior and septal: V2-V4; apical inferior and lateral: LII, LIII and aVF; apex: V2-V4.
CONCLUSIONS
The surface ECG leads with higher ST elevation corresponded to the myocardial segments with more important edema (defined as someone with hyperintensity in the T2- weighted MRI sequence). | pubmed_983_18324 |
pubmed_638_8886 | The rates of Diuron elimination by some advanced oxidation processes (AOPs) such as Fe(III)/UV, Ferrioxalate/UV, Fe(III)/H(2)O(2)/UV, Ferrioxalate/UV/H(2)O(2) and Fe(III)/H(2)O(2) have been compared. Experiments have been conducted at pH=2.3+/-0.1 with a batch reactor equipped with a low-pressure mercury lamp emitting mainly at 253.7 nm. Data obtained under the following experimental conditions ([H(2)O(2)](0)=10(-3)M, [Diuron](0)=5 x 10(-5)M and [Fe(III)](0)=10(-3)M) have shown that rates of Diuron oxidation were higher with the systems Fe(III)/H(2)O(2)/UV and Ferrioxalate/UV/H(2)O(2) than with Fe(III)/UV and Fe(III)/H(2)O(2). On the other hand, Fe(III)/UV was found to be very efficient in mineralization of Diuron solution in comparison to direct UV photolysis. The experimental results showed that radical ()OH is the major pathway in the process of Diuron degradation. | 10.1016/j.jenvman.2007.07.034 |
pubmed_489_15219 | Budding yeast septins assemble into hetero-octamers and filaments required for cytokinesis. Solvent-exposed cysteine (Cys) residues provide sites for attaching substituents useful in assessing assembly kinetics and protein interactions. To introduce Cys at defined locations, site-directed mutagenesis was used, first, to replace the native Cys residues in Cdc3 (C124 C253 C279), Cdc10 (C266), Cdc11 (C43 C137 C138), Cdc12 (C40 C278), and Shs1 (C29 C148) with Ala, Ser, Val, or Phe. When plasmid-expressed, each Cys-less septin mutant rescued the cytokinesis defects caused by absence of the corresponding chromosomal gene. When integrated and expressed from its endogenous promoter, the same mutants were fully functional, except Cys-less Cdc12 mutants (which were viable, but exhibited slow growth and aberrant morphology) and Cdc3(C124V C253V C279V) (which was inviable). No adverse phenotypes were observed when certain pairs of Cys-less septins were co-expressed as the sole source of these proteins. Cells grew less well when three Cys-less septins were co-expressed, suggesting some reduction in fitness. Nonetheless, cells chromosomally expressing Cys-less Cdc10, Cdc11, and Cdc12, and expressing Cys-less Cdc3 from a plasmid, grew well at 30°C. Moreover, recombinant Cys-less septins--or where one of the Cys-less septins contained a single Cys introduced at a new site--displayed assembly properties in vitro indistinguishable from wild-type. | 10.1002/prot.24345 |
pubmed_1129_17750 | Objective
Central venous oxygen saturation (ScvO2) is a measure of the balance between oxygen delivery and consumption. The purpose of this study was to evaluate whether ScvO2 predict weaning success and extubation in simple weaning postcardiac surgical patients.
Material and Method
We prospective observed critically ill post-cardiac surgical patients who were intubated and mechanically ventilated between December 2011 and October 2014. All enrolled patients underwent a spontaneous breathing trial (SBT) before extubation. Arterial and venous blood gas analysis, and hemodynamic and ventilator variables were recorded at the beginning of SBT (T1) and before extubation (T2). Weaning success was defined as successful extubation after SBT without re-intubation within 48 hours. The area under the receiver characteristic curve (ROC) demonstrated the ability to discriminate weaning success. Statistical significance was defined as p<0.05.
Results
A total 121 patients were included. Of these, 18 patients (15%) were re-intubation within 48 hours after extubation. There was no statistically significance in age, gender, and type of operations between those who were extubated successfully and those who were re-intubated within 48 hours. Regarding hemodynamic and respiratory parameters, the significant differences were found only in partial arterial oxygen pressure (PaO2; p = 0.048) and PaO2 to oxygen fraction ratio (PF ratio; p=0.048) at T1. There was no difference between the groups in ScvO2 at either T1 or T2. The area under the ROC (95% confidence interval) of ScvO2 was 0.60 (0.47-0.74) and 0.53 (0.39-0.66) at T1 and T2, respectively. Although ScvO2 was
combined with rapid shallow breathing index (RSBI), PF ratio and minute volume on the regression model at both T1 and T2, the discrimination ability was not significant increased.
Conclusion
ScvO2 or its combination with RSBI, PF ratio and minute volume does not predict successful weaning from mechanical ventilators and extubation in critically ill post-cardiac surgical patients. | pubmed_1129_17750 |
pubmed_614_15467 | BACKGROUND
Sparganosis is an infectious disease caused by the sparganum of Spirometra species, which seldom invades the respiratory system. The aim was to describe the clinical features and outcomes of pulmonary sparganosis.
METHODS
A total of 40 patients with pulmonary sparganosis were reviewed, including 12 cases known from this experience and 28 cases reported in the literature.
RESULTS
Among these 40 patients at an average age of 45.4 ± 11.1 years (men 29), 34 (85%) had a history of ingesting raw or undercooked meat (mainly frogs or snakes). The top 3 symptoms were coughing (60.0%), fever (57.5%) and chest pain (42.5%). Peripheral blood eosinophilia was found in 30 cases (75%). Lesions were located in lung parenchyma, airway, pleura and pulmonary vessels of the patients. Thirty-one patients (77.5%) had pleural effusion. The diagnosis was established by antisparganum antibody test in 30 cases (75%) and by pathology in 9 cases (22.5%); 1 case was not mentioned. Among the 35 cases with follow-up information, 2 treated with complete surgical removal and 31 with oral administration of praziquantel had no recurrence; the remaining 2 died without effective treatments.
CONCLUSIONS
As an extremely rare and life-threatening parasitic zoonosis, pulmonary sparganosis should be diagnosed by combining the epidemiology, patient history, eosinophilia and the positive antisparganum antibody test result together if no worm was detected. Oral praziquantel is considered to be an effective treatment. | 10.1097/MAJ.0000000000000578 |
pubmed_829_22539 | Electronic absorption spectra and Raman spectra of N,N-dimethyl-p-nitroaniline (DMPNA) have been measured in various fluids from the gaseous-like conditions in supercritical fluids (SCFs) to highly polar room-temperature ionic liquids (RTILs). We found that the S0-S1 absorption band center of DMPNA in RTILs is mostly determined by the molar concentrations of ions. On the other hand, the bandwidth of the absorption spectrum does not follow the expectation from a simple dielectric continuum model. Especially in SCFs, the bandwidth of the absorption spectrum decreases with increasing solvent density, suggesting that the intramolecular reorganization energy is a decreasing function of the solvent density. The Raman shift of the NO2 stretching mode has been proven to be a good indicator of the solvent polarity; i.e., the vibrational frequency of the NO2 stretching mode changes from 1340 cm-1 in mostly nonpolar solvent such as ethane to 1300 cm-1 in water. The linear relationship between the absorption band center and the vibrational frequency of the NO2 mode, which was observed for conventional liquids in a previous paper (Fujisawa, T.; Terazima, M.; Kimura, Y. J. Chem. Phys. 2006, 124, 184503), holds almost well for all fluids including SCFs and RTILs. On the other hand, the vibrational bandwidth does not show a simple relationship with the absorption band center. The vibrational bandwidths in RTILs are generally larger in comparison with those in conventional liquids with similar polarity scales. Among the RTILs we investigated, the vibrational bandwidth loosely correlates with the molecular size of the anion. A similar dependence on the anion size is also observed for the bandwidth of the absorption spectrum. We have also investigated the excitation wavelength dependence of the Raman shift of the NO2 stretching mode in RTILs. The extent of the dependence on the excitation wavelength in all fluids is well correlated with the vibrational bandwidth. | 10.1021/jp072020u |
pubmed_757_136 | BACKGROUND
Pituitary adenomas (PAs) are among the most common brain tumors which characteristically become symptomatic due to the mass effect on surrounding structures and/or hormonal imbalances. This study describes 28 cases of PAs with an extrasellar invasive growth (EIG) at the early stage of tumor growth with normal sellar cavity size.
METHODS
1200 cases of PAs either treated medically or via Endoscopic transsphenoidal surgery were reviewed during a 10-year period. Pre-operative imaging was analyzed to evaluate the tumor expansion pattern, tumor invasion sites and other relevant tumor properties. A comprehensive preoperative endocrinological along with postoperative histopathological studies were conducted to evaluate the subjects' homeostasis and further identify the lesions characteristics.
RESULTS
Of the 28 patients, patients 19, 2, 1 and 6 had a growth hormone (GH)-secreting PA, an adrenocorticotropic hormone (ACTH)-secreting PA, a nonfunctional PA (NFPA) and a mix-hormones secreting PA, respectively. There was a statistically significant difference between patients with and without EIG regarding types of PAs (P = 0.000). Post-hoc tests demonstrated that GH-secreting PAs (P = 0.0003) and mix-hormones secreting PAs (P = 0.0000) are significantly more invasive, while NFPAs (P = 0.0000) are less invasive. There was not a statistically significant difference between the invasion sites and different types of PAs (P = 0.122).
CONCLUSION
Among different histological subtypes of PAs, GH-secreting PAs revealed a remarkable tendency for EIG with normal sellar cavity size. The extra-sellar tumor extension with a normal sella did not correlate with atypical histology. Considering EIG patterns, surgeons should be vigilant to investigate and follow the tumor spreading to its enclosing boundary during surgery, the clival part of sphenoid bone should be more exposed, and both inferomedial and lateral borders of the sphenoid sinus should be carefully explored in order to remove the tumor. | 10.1016/j.clineuro.2021.106942 |
pubmed_881_3575 | Synthesis of the neurotrophic factor brain-derived neurotrophic factor (BDNF) and its receptor TrkB in the hippocampus have been proposed to be influenced by endogenous glutamate. To test this hypothesis we have investigated if increases in BDNF and trkB mRNAs are associated with changes in the synaptic release of glutamate in the dorsal hippocampus in the conscious rat by combining the technique of in vivo microdialysis with in situ hybridization histochemistry. A 35% and 66% increase in extracellular levels of glutamate in the dorsal CA1 region was detected following injection into the lateral entorhinal cortex of 2.4 and 9.6 microg of the non-NMDA glutamate receptor agonist quisqualate, respectively. The increase in glutamate was attenuated by local administration of tetrodotoxin (TTX) indicating neuronal origin. Levels of BDNF and trkB mRNAs were increased in the hippocampus in a dose-dependent fashion following the stimulations. The extracellular levels of glutamate in individual animals correlated to the levels of BDNF and trkB mRNAs in the dorsal CA1 region of the hippocampus. This study provides for the first time evidence of an entorhinal cortex influenced concentration-dependent relationship between the release of endogenous glutamate in vivo and neuronal expression of mRNAs for BDNF and its receptor trkB in the hippocampus. | 10.1016/s0169-328x(96)00134-9 |
pubmed_999_6403 | This study investigated disparities in the uptake of telemedicine and the degree of patient-centeredness of telemedicine consultations among vulnerable patient populations. The focus includes rural adults and adults living with psychological distress and a high risk for chronic obstructive pulmonary disease (COPD). In August 2020, a random sample of 932 U.S. adults ≥35 years old with a history of smoking tobacco completed an online survey. Chi-squared analyses were conducted to compare the sociodemographics of participants who did and did not use telemedicine. A series of analysis of variance tests were conducted to examine whether satisfaction with patient-centeredness of telemedicine consultations (i.e., open-endedness, expressed empathy, provider's ability, 5-point Likert scale) differs by rural/urban residence, psychological distress, and COPD risk. About 25% of the sample (n = 240) reported having used telemedicine. Telemedicine use was associated with younger age, Hispanic ethnicity, and moderate-to-high psychological distress, but not rurality. Participants reported high general satisfaction with the patient-centeredness of telemedicine consultations (M = 4.42 ± 0.73). However, high psychological distress and identifying as a current smoker were associated with less satisfaction across all domains. High COPD risk was uniquely associated with less satisfaction in how providers express empathy remotely. Individuals with moderate-to-high psychological distress and a high risk for COPD experience challenges accessing high-quality, patient-centered care via telemedicine. As telemedicine becomes ubiquitous in health care, innovative solutions are needed to overcome barriers that prevent providers from delivering patient-centered care and patients from feeling satisfied with their remote consultations. | 10.1089/tmj.2021.0001 |
pubmed_492_1750 | Pulmonary embolism is a common cardiovascular emergency, but it is still often misdiagnosed due to its unspecific clinical symptoms. Elevated troponin concentrations are associated with greater morbidity and mortality in patients with pulmonary embolism. Right ventricular ischemia due to increased right ventricular afterload is believed to be underlying mechanism of elevated troponin values in acute pulmonary embolism, but a paradoxical coronary artery embolism through opened intra-atrial communication is another possible explanation as shown in our case report. | 10.1186/1476-7120-8-50 |
pubmed_1010_14821 | Attention plays a fundamental role in acquiring and understanding information. Therefore, it is useful to evaluate attention objectively in such fields as education and mental health. Aimed at extracting objective indicators of attention from physiological signals, this study examined the characteristics of electroencephalography (EEG), near-infrared spectroscopy (NIRS), and pupil diameter signals during a free recall task. The objective was to clarify the temporal characteristics of these signals in relation to attention. We used a free recall task as a cognitive task with an attentional load. The participants attempted to memorize and then recall 13 serially presented words. Our hypothesis was that the significant physiological responses should differ depending on the time scale of the attention evaluation. The physiological responses were compared on the basis of differences between success and failure to recall a word on a short time scale, in terms of the attentional state among five serial position groups on a middle time scale, and on the basis of differences between trials with many and few words recalled on a long time scale. We found that the response of each physiological signal depended on the attention in the different time-scale comparisons. (1) The P300 amplitudes of the EEG signals for the words that were recalled were significantly higher than those for the words that were not recalled. (2) Pupillary dilation differed significantly depending on the serial position group. (3) Functional connectivity in the right hemisphere revealed by NIRS was significantly stronger in trials with many words recalled than in those with few words recalled. Different temporal characteristics of physiological signals with respect to attention were suggested by multimodal measurement and multiple-time-scale analysis. Consideration of these characteristics should help in the development of applications requiring objective attention evaluation. | 10.3389/fnins.2019.01307 |
pubmed_876_21267 | The effects of clenbuterol in preserving the form and function of muscle after unilateral sciatic nerve division and epineural repair were investigated in a rat model. The drug (a beta2-adrenoceptor agonist) was administered daily for six weeks by gastric gavage (10 microg/kg body weight), interrupted every 5 days by a 2 day omission of dosing to avoid drug desensitization. Clenbuterol reduced the loss of wet weight, total protein, muscle fibre cross sectional area and (in part) contractile forces in denervated hindlimb muscles, with most effects lasting until reinnervation. The effects were dependent on muscle type, with slow-twitch oxidative muscle (soleus) and mixed-fibre (gastrocnemius) showing greater sensitivity to the drug than fast-twitch muscle (extensor digitorum longus). Anabolic effects on the contralateral innervated muscles tended to be small. The results suggest a potential for the adjuvant use of selective beta -adrenoceptor agonists in the management of peripheral nerve injuries in humans. | 10.1054/jhsb.2001.0603 |
pubmed_85_49 | Postoperative atrial fibrillation (POAF) is a frequent complication of cardiac surgery, which results in increased morbidity, mortality, length of stay, and hospital costs. We developed and followed a process map to implement a protocol to decrease POAF: (1) identify stakeholders and form a working committee, (2) formal literature and guideline review, (3) retrospective analysis of current institutional data, (4) data modeling to determine expected effects of change, (4) protocol development and implementation into the electronic medical record, and (5) ongoing review of data and protocol adjustment. Retrospective analysis demonstrated that POAF occurred in 29.8% of all cardiovascular surgery cases. Median length of stay was 2 days longer (P<0.001), and median total variable costs $2495 higher (P<0.001) in POAF patients. Modeling predicted that up to 60 cases of POAF and >$200 000 annually could be saved. A clinically based electronic medical record tool was implemented into the electronic medical record to aid preoperative clinic providers in identifying patients eligible for prophylactic amiodarone. Initial results during the 9-month period after implementation demonstrated a reduction in POAF in patients using the protocol, compared with those who qualified but did not receive amiodarone and those not evaluated (11.1% versus 38.7% and 38.8%; P=0.022); however, only 17.3% of patients used the protocol. A standardized methodological approach to quality improvement and electronic medical record integration has potential to significantly decrease the incidence of POAF, length of stay, and total variable cost in patients undergoing elective coronary artery bypass graft and valve surgeries. This framework for quality improvement interventions may be adapted to similar clinical problems beyond POAF. | 10.1161/CIRCOUTCOMES.116.003122 |
pubmed_959_540 | BACKGROUND
Cotton stem trichomes and seed fibers are each single celled structures formed by protrusions of epidermal cells, and were found sharing the overlapping molecular mechanism. Compared with fibers, cotton stem trichomes are more easily observed, but the molecular mechanisms underlying their development are still poorly understood.
RESULTS
In this study, Gossypium hirsutum (Gh) and G. barbadense (Gb) were found to differ greatly in percentages of varieties/accessions with glabrous stems and in trichome density, length, and number per trichopore. Gh varieties normally had long singular and clustered trichomes, while Gb varieties had short clustered trichomes. Genetic mapping using five F2 populations from crosses between glabrous varieties and those with different types of stem trichomes revealed that much variation among stem trichome phenotypes could be accounted for by different combinations of genes/alleles on Chr. 06 and Chr. 24. The twenty- six F1 generations from crosses between varieties with different types of trichomes had varied phenotypes, further suggesting that the trichomes of tetraploid cotton were controlled by different genes/alleles. Compared to modern varieties, a greater proportion of Gh wild accessions were glabrous or had shorter and denser trichomes; whereas a smaller proportion of Gb primitive accessions had glabrous stems. A close correlation between fuzz fiber number and stem trichome density was observed in both Gh and Gb primitive accessions and modern varieties.
CONCLUSION
Based on these findings, we hypothesize that stem trichomes evolved in parallel with seed fibers during the domestication of cultivated tetraploid cotton. In addition, the current results illustrated that stem trichome can be used as a morphological index of fiber quality in cotton conventional breeding. | 10.1186/s12870-021-02871-4 |
pubmed_268_10900 | The theory of magnetoencephalography (MEG) and its application to epilepsy research are reviewed briefly. The MEG prediction appears to agree in general with regions where epileptiform discharges are found on the electrocorticogram. MEG appears to have a somewhat better localizing capability than EEG, although MEG may well miss the tangential component of magnetic fields. Thus, the combination of MEG and EEG may be more fruitful than either one alone. | 10.1111/j.1440-1819.1990.tb01402.x |
pubmed_1023_11914 | Neurophysiological investigations of a patient suffering from the stiff-man syndrome revealed that exteroceptive reflexes, in particular those elicited from the skin, were excessively enhanced. In contrast, no abnormalities were found within the monosynaptic reflex arc. Clomipramine injection severely aggravated the clinical symptoms whereas diazepam, clonidine, and tizanidine decreased both muscular stiffness and abnormal exteroceptive reflexes. The hypothesis is put forward that the stiff-man syndrome is a disorder of descending brain-stem systems which exert a net inhibitory control on axial and limb girdle muscle tone as well as on exteroceptive reflex transmission. Detection of abnormal exteroceptive reflex activity in conjunction with neuropharmacological testing might help in the diagnosis of this rare disease. | 10.1136/jnnp.47.3.280 |
pubmed_2_22094 | Use of second generation sequencing (SGS) technologies for transcriptional profiling (RNA-Seq) has revolutionized transcriptomics, enabling measurement of RNA abundances with unprecedented specificity and sensitivity and the discovery of novel RNA species. Preparation of RNA-Seq libraries requires conversion of the RNA starting material into cDNA flanked by platform-specific adaptor sequences. Each of the published methods and commercial kits currently available for RNA-Seq library preparation suffers from at least one major drawback, including long processing times, large starting material requirements, uneven coverage, loss of strand information and high cost. We report the development of a new RNA-Seq library preparation technique that produces representative, strand-specific RNA-Seq libraries from small amounts of starting material in a fast, simple and cost-effective manner. Additionally, we have developed a new quantitative PCR-based assay for precisely determining the number of PCR cycles to perform for optimal enrichment of the final library, a key step in all SGS library preparation workflows. | 10.4161/rna.24284 |
pubmed_722_22418 | In the yeast Saccharomyces cerevisiae, mitochondrial cytochrome c oxidase (COX) biogenesis is translationally regulated. Mss51, a specific COX1 mRNA translational activator and Cox1 chaperone, drives the regulatory mechanism. During translation and post-translationally, newly synthesized Cox1 physically interacts with a complex of proteins involving Ssc1, Mss51, and Cox14, which eventually hand over Cox1 to the assembly pathway. This step is probably catalyzed by assembly chaperones such as Shy1 in a process coupled to the release of Ssc1-Mss51 from the complex. Impaired COX assembly results in the trapping of Mss51 in the complex, thus limiting its availability for COX1 mRNA translation. An exception is a null mutation in COX14 that does not affect Cox1 synthesis because the Mss51 trapping complexes become unstable, and Mss51 is readily available for translation. Here we present evidence showing that Cox25 is a new essential COX assembly factor that plays some roles similar to Cox14. A null mutation in COX25 by itself or in combination with other COX mutations does not affect Cox1 synthesis. Cox25 is an inner mitochondrial membrane intrinsic protein with a hydrophilic C terminus protruding into the matrix. Cox25 is an essential component of the complexes containing newly synthesized Cox1, Ssc1, Mss51, and Cox14. In addition, Cox25 is also found to interact with Shy1 and Cox5 in a complex that does not contain Mss51. These results suggest that once Ssc1-Mss51 are released from the Cox1 stabilization complex, Cox25 continues to interact with Cox14 and Cox1 to facilitate the formation of multisubunit COX assembly intermediates. | 10.1074/jbc.M110.188805 |
pubmed_182_19620 | INTRODUCTION
Pain is a common non-motor feature encountered by patients with Parkinson's disease. Recognition and accurate characterization of pain is crucial for the optimal treatment of Parkinson's disease patients. Pain has been associated with poverty and ethnicity. We determined the prevalence of pain in Parkinson's disease patients in Ethiopia.
METHOD
We conducted a cross-sectional study for a six month period from April 01, 2017-September 30, 2017 with patients with Parkinson's disease who were attending two neurology referral clinics in Addis Ababa, Ethiopia to assess for the prevalence and the characterization of pain.
RESULTS
We surveyed 103 patients with Parkinson's disease. Of these, 87/103 (84%) had symptoms of pain. Only 16/87 (18.4%) received pain medications, and no one was referred for physiotherapy.
CONCLUSION
In Ethiopia, the prevalence of pain in Parkinson's disease patients is amongst the highest in the world, under recognized and undertreated. | 10.1016/j.parkreldis.2018.09.030 |
pubmed_674_6499 | The health benefits of playing football and the importance of exercise and social contact for healthy ageing are well established, but few older adults in the UK take enough exercise. Football is popular, flexible in format and draws players into engrossing, effortful and social exercise, but the physical demands of play at full speed may make it unsustainable for some older adults. Restricted to walking pace, will play still be engaging? Will health benefits be retained? Will physical demands remain manageable? This pilot study aims to investigate: (1) the experience of older adults playing walking football every week, is it sustainable and rewarding, (2) the intensity and locomotor pattern of walking football, (3) the scale and nature of walking football health benefits and (4) possible cognitive benefits of playing walking football through measures of processing speed, selective and divided attention and updating and inhibition components of executive function.
'Walking football' and 'waiting list' groups were compared before and after 12 weeks of one-hour per week football. Walking football was found to be engaging, sustainable for older adults and moderately intensive; however, selective health and cognitive benefits were not found from this brief intervention. Highlights Walking football is a lower impact but authentic form of football that enables older players to extend their active participation. Walking football is enjoyable and moderately demanding and may be a sustainable form of exercise for older adults. Health and cognitive benefits to playing walking football were not found. | 10.1080/17461391.2017.1298671 |
pubmed_71_12550 | Figs (Ficus sp.) are often considered as keystone resources which strongly influence tropical forest ecosystems. We used long-term tree-census data to track the population dynamics of two abundant free-standing fig species, Ficus insipida and F. yoponensis, on Barro Colorado Island (BCI), a 15.6-km2 island in Lake Gatún, Panama. Vegetation cover on BCI consists of a mosaic of old growth (>400 years) and maturing (about 90-150 year old) secondary rainforest. Locations and conditions of fig trees have been mapped and monitored on BCI for more than 35 years (1973-2011), with a focus on the Lutz Catchment area (25 ha). The original distribution of the fig trees shortly after the construction of the Panama Canal was derived from an aerial photograph from 1927 and was compared with previous land use and forest status. The distribution of both fig species (~850 trees) is restricted to secondary forest. Of the original 119 trees observed in Lutz Catchment in 1973, >70% of F. insipida and >90% of F. yoponensis had died by 2011. Observations in other areas on BCI support the trend of declining free-standing figs. We interpret the decline of these figs on BCI as a natural process within a maturing tropical lowland forest. Senescence of the fig trees appears to have been accelerated by severe droughts such as the strong El Niño event in the year 1982/83. Because figs form such an important food resource for frugivores, this shift in resource availability is likely to have cascading effects on frugivore populations. | 10.1371/journal.pone.0177060 |
pubmed_495_3223 | Cholinergic neurotransmission is thought to be modulated by serotonin as documented in animal and human studies. We examined the effects of the muscarinic antagonist scopolamine (0.4 mg IV) given alone or together with the serotonin mixed agonist/antagonist m-chlorophenylpiperazine (m-CPP, 0.08 mg/kg IV), and the selective 5-HT3 receptor antagonist ondansetron (0.15 mg/kg IV). Ten normal elderly volunteers each received five separate pharmacologic challenges (placebo, ondansetron, scopolamine, scopolamine+ondansetron, and scopolamine+m-CPP). Cognitive, behavioral, and physiologic variables were analyzed using repeated measures analysis of variance. The acute effects of scopolamine in certain cognitive, behavioral, and physiological measures were significantly exaggerated by the addition of m-CPP. Scopolamine's cognitive effects were unaffected by ondansetron at the dose tested, nor did ondansetron given alone affect basal cognitive performance. This pilot study suggests that the serotonin mixed agonist/antagonist m-CPP may influence cholinergic neurotransmission. The changes associated with the combination of scopolamine and m-CPP do not appear to be secondary to simple pharmacokinetic alterations and suggest a complex interaction between the cholinergic and serotonergic systems centrally. | 10.1007/BF02311175 |
pubmed_714_9819 | Odontogenic sarcoma is a gnathic malignant connective tissue tumor containing epithelium similar to that seen in an ameloblastoma or ameloblastic fibroma. It is a mixed odontogenic tumor in which the epithelial component is benign and the proliferative mesenchymal component is malignant. With each recurrence, the ameloblastic fibrosarcoma demonstrates increasing evidence of stromal cellularity and mitotic activity but diminishing evidence of odontogenic epithelium. If an ameloblastic fibrosarcoma exhibits dysplastic dentin, it can be called an ameloblastic fibrodentinosarcoma, and if it additionally shows focal deposits of dysplastic enamel proteins, it can be designated an ameloblastic fibro-odontosarcoma. A jaw tumor displaying both a carcinomatous and a malignant spindle cell component can be termed an odontogenic carcinosarcoma if it reveals an ameloblastic fibroma-like pattern. If it lacks this pattern, the appellations "spindle-cell ameloblastic carcinoma" or "biphasic ameloblastic sarcomatoid carcinoma" might be preferable. This is a US government work. There are no restrictions on its use. | pubmed_714_9819 |
pubmed_1066_21123 | The spatiotemporal organization of chromatin is regulated at different levels in the nucleus. Epigenetic modifications such as DNA methylation and histone modifications are involved in chromatin regulation and play fundamental roles in genome function. While the one-dimensional epigenomic landscape in many cell types has been revealed by chromatin immunoprecipitation and sequencing, the dynamic changes of chromatin modifications and their relevance to chromatin organization and genome function remain elusive. Live-cell probes to visualize chromatin and its modifications have become powerful tools to monitor dynamic chromatin regulation. Bulk chromatin can be visualized by both small fluorescent dyes and fluorescent proteins, and specific endogenous genomic loci have been detected by adapting genome-editing tools. To track chromatin modifications in living cells, various types of probes have been developed. Protein domains that bind weakly to specific modifications, such as chromodomains for histone methylation, can be repeated to create a tighter binding probe that can then be tagged with a fluorescent protein. It has also been demonstrated that antigen-binding fragments and single-chain variable fragments from modification-specific antibodies can serve as binding probes without disturbing cell division, development and differentiation. These modification-binding modules are used in modification sensors based on fluorescence/Förster resonance energy transfer to measure the intramolecular conformational changes triggered by modifications. Other probes can be created using a bivalent binding system, such as fluorescence complementation or luciferase chemiluminescence. Live-cell chromatin modification imaging using these probes will address dynamic chromatin regulation and will be useful for assaying and screening effective epigenome drugs in cells and organisms. | 10.1093/jmicro/dfab030 |
pubmed_450_4041 | A common genetic alteration in acute myeloid leukemia is the internal tandem duplication (ITD) in FLT3, the receptor for cytokine FLT3 ligand (FLT3L). Constitutively active FLT3-ITD promotes the expansion of transformed progenitors, but also has pleiotropic effects on hematopoiesis. We analyzed the effect of FLT3-ITD on dendritic cells (DCs), which express FLT3 and can be expanded by FLT3L administration. Pre-leukemic mice with the Flt3(ITD) knock-in allele manifested an expansion of classical DCs (cDCs) and plasmacytoid DCs. The expansion originated in DC progenitors, was cell intrinsic, and was further enhanced in Flt3(ITD/ITD) mice. The mutation caused the down-regulation of Flt3 on the surface of DCs and reduced their responsiveness to Flt3L. Both canonical Batf3-dependent CD8(+) cDCs and noncanonical CD8(+) cDCs were expanded and showed specific alterations in their expression profiles. Flt3(ITD) mice showed enhanced capacity to support T cell proliferation, including a cell-extrinsic expansion of regulatory T (T reg) cells. Accordingly, these mice restricted alloreactive T cell responses during graft-versus-host reaction, but failed to control autoimmunity without T reg cells. Thus, the FLT3-ITD mutation directly affects DC development, indirectly modulating T cell homeostasis and supporting T reg cell expansion. We hypothesize that this effect of FLT3-ITD might subvert immunosurveillance and promote leukemogenesis in a cell-extrinsic manner. | 10.1084/jem.20150642 |
pubmed_490_14814 | The intracellular proinflammatory mediator IL-32 is associated with tumor progression; however, the mechanisms remain unknown. We studied IL-32 mRNA expression as well as expression of other proinflammatory cytokines and mediators, including IL-1α, IL-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, the proangiogenic and antiapoptotic enzyme cyclooxygenase-2, the IL-8 receptor C-X-C chemokine receptor (CXCR) 1, and the intracellular kinase focal adhesion kinase-1. The interaction of IL-32 expression with expression of IL-6, TNF-α, IL-8, and cyclooxygenase-2 was also investigated. Biopsy specimens of 11 HIV-related, 7 non-HIV-related Kaposi sarcoma (KS), and 7 normal skin tissues (NSTs) of Dutch origin were analyzed. RNA was isolated from the paraffin material, and gene expression levels of IL-32 α, β, and γ isoforms, IL1a, IL1b, IL6, IL8, TNFA, PTGS2, CXCR1, and PTK2 were determined using real-time quantitative PCR. Significantly higher expression of IL-32β and IL-32γ isoforms was observed in HIV-related KS biopsy specimens compared with non-HIV-related KS and NST. The splicing ratio of the IL-32 isoforms showed IL-32γ as the highest expressed isoform, followed by IL-32β, in HIV-related KS cases compared with non-HIV-related KS and NST. Our data suggest a possible survival mechanism by the splicing of IL-32γ to IL-32β and also IL-6, IL-8, and CXCR1 signaling pathways to reverse the proapoptotic effect of the IL-32γ isoform, leading to tumor cell survival and thus favoring tumor progression. | 10.1016/j.ajpath.2017.08.033 |
pubmed_760_23645 | The acoustic properties of an air-saturated macroscopically inhomogeneous aluminum foam in the equivalent fluid approximation are studied. A reference sample built by forcing a highly compressible melamine foam with conical shape inside a constant diameter rigid tube is studied first. In this process, a radial compression varying with depth is applied. With the help of an assumption on the compressed pore geometry, properties of the reference sample can be modelled everywhere in the thickness and it is possible to use the classical transfer matrix method as theoretical reference. In the mixture approach, the material is viewed as a mixture of two known materials placed in a patchwork configuration and with proportions of each varying with depth. The properties are derived from the use of a mixing law. For the reference sample, the classical transfer matrix method is used to validate the experimental results. These results are used to validate the mixture approach. The mixture approach is then used to characterize a porous aluminium for which only the properties of the external faces are known. A porosity profile is needed and is obtained from the simulated annealing optimization process. | 10.1121/1.4965300 |
pubmed_917_14836 | The existence of distinct 69- and 100-kDa forms of 2-5A-synthetase in addition to the smaller (40 and 46 kDa) forms has recently been established. Using specific monoclonal antibodies we investigated the induction, synthesis, and activity of 69- and 100-kDa 2',5'-oligoadenylate (2-5A) synthetases in interferon-treated human Daudi cells. Although induction of these synthetases is detectable in cells treated with as little as 1-5 units/ml of human alpha-interferon, higher concentrations are required for maximum synthesis of the 100 kDa than the 69-kDa protein. At 5 units/ml of interferon, enhanced synthesis of both proteins is detectable at 4 h with maximum synthesis occurring between 8 to 12 and 12 to 16 h for 69- and 100-kDa 2-5A-synthetases, respectively. At 24 h after addition of interferon, synthesis of these synthetases declines due to a decrease of active interferon in the culture medium. The synthesis of both synthetases is blocked by actinomycin D, and the half-life of these proteins is estimated to be 8 h. The activities of immunoaffinity purified 69- and 100-kDa synthetases are dependent on double-stranded (ds)RNA but show different requirements for optimum concentration of dsRNA and pH of the reaction. The apparent Km of 69- and 100-kDa synthetases for ATP is 1.7 X 10(-3) M and 3.6 X 10(-3) M, respectively. At optimum conditions for the activity of these enzymes, the pattern of 2',5'-linked oligoadenylates synthesized are different, the 69-kDa protein synthesizing higher oligomers than the 100-kDa species. Taken together, these results indicate that the 69- and 100-kDa 2-5A-synthetases are distinct proteins each with specific characteristics of induction and enzymatic activity. | pubmed_917_14836 |
pubmed_341_24243 | West Nile virus (WNV) is an emerging mosquito-borne flavivirus, related to dengue virus and Zika virus. To gain insight into host pathways involved in WNV infection, we performed a systematic affinity-tag purification mass spectrometry (APMS) study to identify 259 WNV-interacting human proteins. RNA interference screening revealed 26 genes that both interact with WNV proteins and influence WNV infection. We found that WNV, dengue and Zika virus capsids interact with a conserved subset of proteins that impact infection. These include the exon-junction complex (EJC) recycling factor PYM1, which is antiviral against all three viruses. The EJC has roles in nonsense-mediated decay (NMD), and we found that both the EJC and NMD are antiviral and the EJC protein RBM8A directly binds WNV RNA. To counteract this, flavivirus infection inhibits NMD and the capsid-PYM1 interaction interferes with EJC protein function and localization. Depletion of PYM1 attenuates RBM8A binding to viral RNA, suggesting that WNV sequesters PYM1 to protect viral RNA from decay. Together, these data suggest a complex interplay between the virus and host in regulating NMD and the EJC. | 10.1038/s41564-019-0375-z |
pubmed_1014_23521 | Marek's disease is one of the most common viral diseases of poultry affecting chicken flocks worldwide. The disease is caused by an alphaherpesvirus, the Marek's disease virus (MDV), and is characterized by the rapid onset of multifocal aggressive T-cell lymphoma in the chicken host. Although several viral oncogenes have been identified, the detailed mechanisms underlying MDV-induced lymphomagenesis are still poorly understood. Many viruses modulate cell cycle progression to enhance their replication and persistence in the host cell, in the case of some oncogenic viruses ultimately leading to cellular transformation and oncogenesis. In the present study, we found that MDV, like other viruses, is able to subvert the cell cycle progression by triggering the proliferation of low proliferating chicken cells and a subsequent delay of the cell cycle progression into S-phase. We further identified the tegument protein VP22 (pUL49) as a major MDV-encoded cell cycle regulator, as its vector-driven overexpression in cells lead to a dramatic cell cycle arrest in S-phase. This striking functional feature of VP22 appears to depend on its ability to associate with histones in the nucleus. Finally, we established that VP22 expression triggers the induction of massive and severe DNA damages in cells, which might cause the observed intra S-phase arrest. Taken together, our results provide the first evidence for a hitherto unknown function of the VP22 tegument protein in herpesviral reprogramming of the cell cycle of the host cell and its potential implication in the generation of DNA damages. | 10.1371/journal.pone.0100004 |
pubmed_857_17333 | A new method of estimating pharmacokinetic parameters for enterohepatic recirculation models is presented. The algorithm, based on the simplex method, assures a convergence toward the minimum minimorum; provides reliable parameters, even in large numbers; and handles up to five cycle effects in five established models: IV, EV, mono-, bi- or tricompartmental. For each model, the reabsorption rate may be considered to be slow (characterised by a rate constant with a significant value) or instantaneous (an infinite rate constant). Two examples are given to illustrate the qualities of the software that incorporates this new algorithm. The first relates to the pharmacokinetics of zinc orally given to humans; the second treats the kinetics of alpha-methylDOPA given to dogs intra-arterially (note: values of plasma concentrations have been extracted from the literature). | 10.1007/BF03188787 |
pubmed_530_15028 | UNLABELLED
PREMISE OF THE STUDY
Microsatellite primers were developed in Iris ensata (Iridaceae) to provide polymorphic markers for further studies into population genetics. •
METHODS AND RESULTS
Thirteen polymorphic microsatellite loci were isolated from I. ensata. These loci were successfully amplified in two natural populations of I. ensata from eastern China (Longwangshan, Zhejiang Province) and northeastern China (Jinchuan, Jilin Province). There was no significant linkage disequilibrium found for any pair of loci. These loci contained between two and 12 alleles per locus across all 48 individuals of I. ensata. The number of alleles per locus varied from two to 10 at the population level and the observed and expected heterozygosities ranged from 0.167 to 0.958 and from 0.284 to 0.853, respectively. •
CONCLUSIONS
These loci showed high levels of polymorphism and could be used to study the population genetic structure, genetic relationships, and phylogeography of I. ensata. | 10.3732/ajb.1200266 |
pubmed_188_9838 | Campylobacter jejuni, a major cause of bacterial foodborne illnesses, is considered highly susceptible to environmental stresses. In this study, we extensively investigated the stress tolerance of 121 clinical strains of C. jejuni against 5 stress conditions (aerobic stress, disinfectant exposure, freeze-thaw, heat treatment, and osmotic stress) that this pathogenic bacterium might encounter during foodborne transmission to humans. In contrast to our current perception about high stress sensitivity of C. jejuni, a number of clinical strains of C. jejuni were highly tolerant to multiple stresses. We performed population genetics analysis by using comparative genomic fingerprinting and showed that multistress-tolerant strains of C. jejuni constituted distinct clades. The comparative genomic fingerprinting subtypes belonging to multistress-tolerant clades were more frequently implicated in human infections than those in stress-sensitive clades. We identified unique stress-tolerant C. jejuni clones and showed the role of stress tolerance in human campylobacteriosis. | 10.3201/eid2406.171587 |
pubmed_715_14663 | OBJECTIVE
To study the methods of differential diagnosis between mucosa-associated lymphoid tissue (MALT) type lymphoma and reactive lymphoid hyperplasia in ocular adnexa.
METHODS
The clinical, morphologic, immunohistochemical, and molecular biologic (polymerase chain reaction [PCR]) studies were performed on 29 patients with MALT-type lymphoma and 8 patients with reactive lymphoid hyperplasia of the ocular adnexa.
RESULTS
29 cases with MALT-type lymphoma expressed B-cell markers and but T-cell makers, whereas 8 cases of reactive lymphoid hyperplasia all expressed B and T cell markers and the positive rate of T-cell marker was up to 30%. immunohistochemistry staining showed 11 cases were positive for immunoglobin light chain (kappa or lambda), however it was positive in one chain of the immunoglobin in 15 cases of MALT type lymphoma by PCR. No significant difference in the clinical characteristics was observed between the MALT type lymphoma and reactive lymphoid hyperplasia in ocular adnexa.
CONCLUSION
Immunohistochemical analysis and PCR are helpful in confirming the diagnosis between the MALT-lymphoma and the reactive lymphoid hyperplasia. | pubmed_715_14663 |
pubmed_692_9655 | CONTEXT
Saponinum album (SA) is a complex mixture of triterpenoid saponins previously shown to augment the cytotoxicity of the type I ribosome-inactivating protein saporin and an EGF-saporin target toxin that could potentially be used to improve the therapeutic window of targeted toxins.
OBJECTIVE
To investigate the augmentative property of SA on saporin and saporin-based immunotoxins (IT) directed against five different cell surface target molecules on human leukemia and lymphoma cells.
MATERIALS AND METHODS
After determining the optimum dose of SA for each cell line, the extent of SA-mediated augmentation was established for saporin and five saporin-based ITs using XTT and an annexin V apoptosis assay. Immunospecificity was investigated using three different blocking assays. Dose-scheduling was also investigated using the XTT assay.
RESULTS
Uncorrected SA-mediated augmentation ranged at best from 31.5 million-fold to, at worse, 174-fold. However, when the calculated fold-increases were adjusted for the non-immunospecific effects of SA on an off-target IT, the true augmentative effects of SA were found to be largely non-immunospecific. Antibody blocking studies demonstrated that the augmentative effect of SA was only partially immunospecific. Separate exposure of target cells to IT and SA at different times demonstrated that immunospecific augmentation of IT by SA could be achieved but only if cells were exposed to IT first and SA second.
CONCLUSIONS
SA significantly, although variably, augments the cytotoxicity of saporin and saporin-based immunotoxins. Concomitant exposure to both IT and SA can result in non-immunospecific cytotoxicity that can be overcome by temporally separating exposure to each. | 10.3109/08923973.2014.971964 |
pubmed_946_13135 | Patients with enhanced catabolism of prednisolone exhibit a reduction in steroid efficacy. Since prednisolone never reaches steady state at the usual dosage, the clearance rate can only be estimated by determining the area under the plasma concentration-time curve after an i.v. dose of prednisolone. To obviate that time-consuming procedure for screening of patients with enhanced prednisolone metabolism, we developed a quantitative assay for 6 beta-hydroxyprednisolone in urine to determine whether the urinary excretion of 6 beta-hydroxyprednisolone increases concomitantly with the clearance rate of total and of unbound prednisolone in subjects with an enhanced catabolism of prednisolone. The results are given separately for males and females because there is some debate as to whether females compared to males exhibit a higher capacity of the liver to hydroxylate steroids at the sixth position. Before and during the administration of phenytoin the total body clearance of total and of unbound prednisolone and the urinary excretion of prednisolone and of 6 beta-hydroxyprednisolone were determined in six female and eight male volunteers. The fraction of the i.v. dose of prednisolone excreted in urine as 6 beta-hydroxyprednisolone was higher in females than in males (p less than 0.001) and increased during phenytoin dosing from 6.4%-10.4% (range) to 15.6%-20.4% in females and from 2.4%-7.2% to 12.2%-18.3% in males. The ratio of 6 beta-hydroxyprednisolone to prednisolone in urine increased linearly with the nonrenal clearance of both total and unbound prednisolone. This is the first demonstration that the fractional excretion of 6 beta-hydroxyprednisolone increased after the induction of the microsomal liver enzymes. Thus measurements of urinary 6 beta-hydroxyprednisolone excretion may be of potential value to detect patients with enhanced catabolism of prednisolone. | pubmed_946_13135 |
pubmed_468_7939 | Dendritic cells (DC) are the most potent antigen presenting cells capable of initiating T-cell-dependent immune responses (1-5). This biologic potential can be harnessed to elicit effective antigen-specific immune responses by transferring the relevant antigens to the DC. Once the DC have been mobilized and purified, the relevant antigens can be transferred to the DC as intact proteins, or as peptides representing specific epitopes, or with gene transfer using sequences of DNA or RNA coding for the pertinent antigen(s) (6-15). Theoretically, genetically modifying DC with genes coding for specific antigens has potential advantages over pulsing the DC with peptides repeating the antigen or antigen fragment. First, the genetically modified DC may present previously unknown epitopes in association with different MHC molecules. Second, gene transfer to DC ensures that the gene product is endogenously processed, leading to the generation of MHC class I-restricted cytotoxic T lymphocytes (CTL), the effector arm of cell-mediated immune responses. Finally, in addition to genes coding for the antigen(s), genetic modification of the DC can induce genes coding for mediators relevant to generation of the immune response to the antigen(s), further boosting host responses to the antigens presented by the modified DC. Different gene transfer approaches have been explored to genetically modify DC, including retroviral vectors (16-18), recombinant vaccinia virus vectors (19), and recombinant adenovirus (Ad) vectors (19-23). The focus of this chapter is on using recombinant Ad vectors to transfer genes to murine DC. We have used a similar strategy to transfer genes to human DC (24). As an example of the power of this technology, we will describe the use of Ad-vector-modified DC to suppress the growth of tumor cells modified to express a specific antigen. | 10.1385/1-59259-150-7:429 |
pubmed_435_14312 | To determine the overall survival (OS) in patients who underwent planned trimodality therapy (TMT) and those who underwent definitive concurrent chemoradiation (CRT), but later received salvage resection (SR) for stage IIIA (cN2) (AJCC 7th ed.) non-small cell lung cancer. National Cancer Database data set from 2004 to 2014 was queried. TMT was defined as multiagent CRT with dose >45 Gy, followed by lobectomy or pneumonectomy ≤90 days from end of CRT. SR was defined as multiagent CRT with dose >59 Gy and lobectomy or pneumonectomy performed >90 days from CRT completion. Propensity score weighting and propensity score matching methods were used to balance patient and tumor characteristics and to calculate hazard ratios. A total of 2025 (1899 TMT and 126 SR) patients were analyzed. TMT and SR groups shared similar characteristics. Surgery occurred at a median of 41 days (range 1-90) after CRT in the TMT group and 114 days (91-440) in the SR group. The 90-day mortality after surgery was 6.5% for TMT and 5% for SR (P = 0.43). The 3- and 5-year OS were 55.1% and 35.7% for TMT and 51.6% and 45.0% for SR (P = 0.92, 0.68), with no difference across unadjusted cohort and propensity-adjusted cohort. Patients with cN2 stage IIIA non-small cell lung cancer treated in the United States with definitive CRT followed by SR had similar OS as upfront TMT with similar postoperative mortality despite SR occurring >90 days after >59 Gy CRT. SR remains an option for medically appropriate patients after definitive dose CRT. | 10.1053/j.semtcvs.2019.06.002 |
pubmed_443_20364 | In this article, we document flow disturbance due to internal thoracic artery spasm (ITA) in a patient undergoing minimally invasive coronary artery grafting. We used intraoperative duplex scanning. Application of systemic vasodilators resulted in rapid improvement of ITA flow, as demonstrated by serial duplex examinations. | 10.1111/j.1540-8191.1997.tb00159.x |
pubmed_919_89 | WNK1 (with no lysine (K) 1) is a protein-serine/threonine kinase with a unique catalytic site organization. Deletions in the first intron of the WNK1 gene were found in a group of hypertensive patients with pseudohypoaldosteronism type II. No changes in coding sequence of WNK1 were found, but its expression was increased severalfold. We have been investigating actions of WNK1 and have found that WNK1 activates the serum- and glucocorticoid-induced protein kinase SGK1, which impacts membrane expression of the epithelial sodium channel. Here we explore the role of WNK1 in SGK1 regulation. Activation of SGK1 by WNK1 is blocked by phosphatidylinositol 3-kinase inhibitors. Neither the catalytic activity nor the kinase domain of WNK1 is required; rather the N-terminal 220 residues of WNK1 are necessary and sufficient to activate SGK1. Phosphorylation of WNK1 on Thr-58 contributes to SGK1 activation. Finally, we show that WNK1 is required for the activation of SGK1 by insulin-like growth factor 1. | 10.1074/jbc.M505735200 |
pubmed_720_11030 | BACKGROUND
Abnormal calcium (Ca2+) release from the sarcoplasmic reticulum (SR) contributes to the pathogenesis of atrial fibrillation (AF). Increased phosphorylation of 2 proteins essential for normal SR-Ca2+ cycling, the type-2 ryanodine receptor (RyR2) and phospholamban (PLN), enhances the susceptibility to AF, but the underlying mechanisms remain unclear. Protein phosphatase 1 (PP1) limits steady-state phosphorylation of both RyR2 and PLN. Proteomic analysis uncovered a novel PP1-regulatory subunit (PPP1R3A [PP1 regulatory subunit type 3A]) in the RyR2 macromolecular channel complex that has been previously shown to mediate PP1 targeting to PLN. We tested the hypothesis that reduced PPP1R3A levels contribute to AF pathogenesis by reducing PP1 binding to both RyR2 and PLN.
METHODS
Immunoprecipitation, mass spectrometry, and complexome profiling were performed from the atrial tissue of patients with AF and from cardiac lysates of wild-type and Pln-knockout mice. Ppp1r3a-knockout mice were generated by CRISPR-mediated deletion of exons 2 to 3. Ppp1r3a-knockout mice and wild-type littermates were subjected to in vivo programmed electrical stimulation to determine AF susceptibility. Isolated atrial cardiomyocytes were used for Stimulated Emission Depletion superresolution microscopy and confocal Ca2+ imaging.
RESULTS
Proteomics identified the PP1-regulatory subunit PPP1R3A as a novel RyR2-binding partner, and coimmunoprecipitation confirmed PPP1R3A binding to RyR2 and PLN. Complexome profiling and Stimulated Emission Depletion imaging revealed that PLN is present in the PPP1R3A-RyR2 interaction, suggesting the existence of a previously unknown SR nanodomain composed of both RyR2 and PLN/sarco/endoplasmic reticulum calcium ATPase-2a macromolecular complexes. This novel RyR2/PLN/sarco/endoplasmic reticulum calcium ATPase-2a complex was also identified in human atria. Genetic ablation of Ppp1r3a in mice impaired binding of PP1 to both RyR2 and PLN. Reduced PP1 targeting was associated with increased phosphorylation of RyR2 and PLN, aberrant SR-Ca2+ release in atrial cardiomyocytes, and enhanced susceptibility to pacing-induced AF. Finally, PPP1R3A was progressively downregulated in the atria of patients with paroxysmal and persistent (chronic) AF.
CONCLUSIONS
PPP1R3A is a novel PP1-regulatory subunit within the RyR2 channel complex. Reduced PPP1R3A levels impair PP1 targeting and increase phosphorylation of both RyR2 and PLN. PPP1R3A deficiency promotes abnormal SR-Ca2+ release and increases AF susceptibility in mice. Given that PPP1R3A is downregulated in patients with AF, this regulatory subunit may represent a new target for AF therapeutic strategies. | 10.1161/CIRCULATIONAHA.119.039642 |
pubmed_564_7741 | We present two cases of outpatient behavioural psychotherapy of frontal-lobe brain-injured adults. Unlike inpatient treatment of severely frontal-injured patients in which the hospital setting acts on the patient to modify behaviour, outpatient treatment teaches the self-motivated individual to use the structure and directiveness of behavioural psychotherapy to overcome his or her neuropsychological deficits. The literature describes two types of frontal syndromes: disinhibition and adynamia. Treatment of both types of syndromes is illustrated using case presentations. The therapeutic interventions for both syndromes are designed to exaggerate the link between stimulus and response to counter impaired processing of feedback. A six-stage behavioural psychotherapy model of the frontal-injured patient is outlined. | 10.3109/02699059309008179 |
pubmed_190_11620 | OBJECTIVE
To clarify whether early occupational therapy for patients with acute schizophrenia improves their functional independence.
DESIGN
Quasi-experimental controlled study.
SETTING
A university hospital in Japan.
SUBJECTS
Forty-six out of 85 eligible patients with schizophrenia.
INTERVENTION
Participants were allocated into an intervention group or a control group according to the month of admission. Activities in one-on-one and mainly non-verbal occupational therapy were provided for the intervention group immediately after admission, and not for the control group.
MAIN MEASURES
Functional independence was measured using the Functional Independence Measure (FIM), at admission, at one month and at three months after admission. Psychiatric symptoms were also measured by the Brief Psychiatric Rating Scale.
RESULTS
Patients in both groups showed improved FIM total scores at one month and three months after admission. In the intervention group, the medians (interquartile ranges) were 89.0 (44.5) at admission, 113.0 (18.5) at one month, and 121.0 (6.5) at three months. In the control group, they were 88.0 (32.0), 107.0 (39.5), and 111.0 (17.0). At three months, the total FIM scores were significantly higher in the intervention group than in the control group (p = 0.016). In the FIM cognitive domain, the scores were significantly higher in the intervention group than in the control group at one month (p = 0.038) and, three months (p = 0.012). Both groups showed improvement in Brief Psychiatric Rating Scale total scores, while no significant differences were observed between the groups at any points.
CONCLUSION
The results suggest that early occupational therapy may improve functional independence in patients with acute schizophrenia. | 10.1177/0269215514521440 |
pubmed_10_13277 | The title compound, nonasodium chromium(III) hexakis[molybdate(VI)], β-Na9CrMo6O24, was prepared by solid-state reactions. This alluaudite-type structure is constituted of infinite layers formed by links between M 2O10 (M = C/Na) dimers and MoO4 tetra-hedra. The Na(+) and Cr(3+) cations are located in the same site with, respectively, 0.25 and 0.75 occupancies. The layers are connected to each other through MoO4 sharing corners, resulting an in open three-dimensional framework with hexa-gonal-form cavities occupied by Na(+) cations. The proposed structural model is supported by charge-distribution (CHARDI) and bond-valence-sum (BVS) analysis. All atoms are on general positions except for one Mo, two Na (site symmetry 2) and another Na site (site symmetry -1). A comparison is made with the similar structures Na4Co(MoO4)3, Na2Ni(MoO4)2, Cu1.35Fe3(PO4)3 and NaAgFeMn2(PO4)3. | 10.1107/S205698901600774X |
pubmed_1039_5709 | Leaf tissue from plants infected with Festuca leaf streak virus was extracted with a buffer containing a nonionic detergent; this treatment released the G protein from the nucleocapsid of virions. The extract was tested with antiserum by double immunodiffusion for G protein and by immunosorbent electron microscopy with 'decoration' for nucleocapsid antigens. Clear homologous reactions were obtained. No heterologous reactions were observed with similar preparations of barley yellow striate mosaic, northern cereal mosaic, and cereal chlorotic mottle viruses. | 10.1159/000149533 |
pubmed_521_4869 | The number of tRNA binding sites in 80S ribosomes from Saccharomyces cerevisiae was assessed by means of tRNA saturation and translocation experiments. In the absence of cognate mRNA yeast ribosomes could bind 0.6 [32P]tRNA(Phe) per 80S while poly(U) programmed ribosomes accepted up to 1.7 tRNA(Phe) molecules per 80S or 0.5 molecules of Ac[14C]Phe-tRNA(Phe) per 80S. Compared with the known features of E. coli ribosomes these binding values indicated both the presence of three tRNA binding sites and the validity of the exclusion principle for peptidyl-tRNA binding to yeast ribosomes. Upon EF-2 dependent translocation of a complex containing deacyl-tRNA in the P-site and AcPHe-tRNA in the A-site, the deacylated tRNA does not leave the ribosome quantitatively. This observation suggests the presence of an E site in 80S ribosomes which is functionally equivalent to the one previously characterized in prokaryotic systems. | pubmed_521_4869 |
pubmed_634_10682 | Lipid accumulation in white adipose tissue is the key contributor to the obesity and orchestrates numerous metabolic health problems such as type 2 diabetes, hypertension, atherosclerosis, and cancer. Nonetheless, the prevention and treatment of obesity are still inadequate. Recently, scientists found that brown adipose tissue (BAT) in adult humans has functions that are diametrically opposite to those of white adipose tissue and that BAT holds promise for a new strategy to counteract obesity. In this study, we evaluated the potential of sinapic acid (SA) to promote the thermogenic program and lipolysis in BAT. SA treatment of brown adipocytes induced the expression of brown-adipocyte activation-related genes such as Ucp1, Pgc-1α, and Prdm16. Furthermore, structural analysis and western blot revealed that SA upregulates protein kinase A (PKA) phosphorylation with competitive inhibition by a pan-PKA inhibitor, H89. SA binds to the adenosine triphosphate (ATP) site on the PKA catalytic subunit where H89 binds specifically. PKA-cat-α1 gene-silencing experiments confirmed that SA activates the thermogenic program via a mechanism involving PKA and cyclic AMP response element-binding protein (CREB) signaling. Moreover, SA treatment promoted lipolysis via a PKA/p38-mediated pathway. Our findings may allow us to open a new avenue of strategies against obesity and need further investigation. [BMB Reports 2020; 53(3): 142-147]. | pubmed_634_10682 |
pubmed_371_18797 | The enantiospecific determination of R- and S-hexobarbital in rat plasma is described. The method involves liquid-liquid extraction of racemic hexobarbital from plasma, separation of the underivatized enantiomers by high-performance liquid chromatography on an alpha 1-acid glycoprotein column and ultraviolet detection. The mobile phase consists of a phosphate buffer (pH 5.4) containing 0.4% 2-propanol as organic modifier. An alpha 1-acid glycoprotein guard column is used to increase the lifetime of the analytical column. Heptabarbital is the achiral internal standard. With detection limits of ca. 0.05 microgram/ml for both R- and S-hexobarbital, the assay is suitable for pharmacokinetic studies of the enantiomers in rats. | 10.1016/0378-4347(91)80154-5 |
pubmed_1054_4871 | The thymic rudiment was removed from the mouse embryo at 10 days of gestation, while it was still included in the 3rd branchial arch. When cultured alone, either in vitro or on the chick chorioallantoic membrane (CAM), it failed to develop as a lymphopoietic organ and remained in an epithelial state. If it was associated in transfilter culture with various types of hemopoietic organs from either embryonic or adult mice (e.g. yolk sac, fetal liver, thymus, bone marrow), it became seeded by lymphoid precursor cells and underwent a normal histogenetic process. If the donor and the receptor explants belonged to different strains of mice, the thymus that developed in culture was chimeric: thymic stroma cells (i.e., epithelial and connective cells) were of the receptor explant type, whereas the lymphoid population was of the donor type. Two genetic markers were used to label the thymic cell types, the Thy-1-1-Thy-1-2 system and the isozymes of the glucose phosphate isomerase. | pubmed_1054_4871 |
pubmed_332_530 | Mechanotransduction has demonstrated potential for regulating tissue adaptation in vivo and cellular activities in vitro. It is well documented that ultrasound can produce a wide variety of biological effects in biological systems. For example, pulsed ultrasound can be used to noninvasively accelerate the rate of bone fracture healing. Although a wide range of studies has been performed, mechanism for this therapeutic effect on bone healing is currently unknown. To elucidate the mechanism of cellular response to mechanical stimuli induced by pulsed ultrasound radiation, we developed a method to apply focused acoustic radiation force (ARF) (duration, one minute) on osteoblastic MC3T3-E1 cells and observed cellular responses to ARF using a spinning disk confocal microscope. This study demonstrates that the focused ARF induced F-actin cytoskeletal rearrangement in MC3T3-E1 cells. In addition, these cells showed an increase in intracellular calcium concentration following the application of focused ARF. Furthermore, passive bending movement was noted in primary cilium that were treated with focused ARF. Cell viability was not affected. Application of pulsed ultrasound radiation generated only a minimal temperature rise of 0.1°C, and induced a streaming resulting fluid shear stress of 0.186 dyne/cm(2), suggesting that hyperthermia and acoustic streaming might not be the main causes of the observed cell responses. In conclusion, these data provide more insight in the interactions between acoustic mechanical stress and osteoblastic cells. This experimental system could serve as basis for further exploration of the mechanosensing mechanism of osteoblasts triggered by ultrasound. | 10.1371/journal.pone.0038343 |
pubmed_78_10620 | Selective toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a parkinsonism inducing compound, is well known to be related to an uptake of its active metabolite MPP+ into dopaminergic neurons by dopamine transporter (DAT). The aim of the present study was to examine whether paraquat, a commonly used herbicide, which is an 1-methyl-4-phenyl-pyridinium ion (MPP+) analogue, affects DAT in vivo in rats. Paraquat administered at a dose of 10 mg/kg ip decreased the binding of [3H]GBR 12,935 to DAT measured by quantitative autoradiography in the dorsal and ventral caudate-putamen, but not in the substantia nigra pars compacta. Moreover, this compound increased the level of 3-methoxytyramine (3-MT) and 3-MT/dopamine ratio in the anterior and posterior caudate-putamen measured by HPLC with electrochemical detection. No other alterations in the levels of dopamine and its metabolites were found in the caudate-putamen and substantia nigra. The present study seems to suggest that systemic paraquat administration affects striatal DAT and dopamine metabolism in the nigrostriatal neurons in rats which may be crucial for its neurotoxic effects on dopaminergic neurons. | pubmed_78_10620 |
pubmed_229_21640 | INTRODUCTION
Thoracoabdominal aortic replacement requires visceral vessel revascularization and is usually performed with Crawford's inclusion technique or a large Carrel patch. This segment of retained native aorta may be prone to recurrent aneurysmal disease. We reviewed our experience with patients in whom aneurysmal expansion of the visceral patch was detected.
METHODS
The records of 107 patients undergoing thoracoabdominal aortic replacement operations performed or followed up at the Johns Hopkins Hospital between 1992 and 2000 were reviewed. All patients had visceral patches created for type II, III, or IV aneurysms. Visceral patches were considered aneurysmal if the maximal diameter of the aortic prosthesis and patch was 4.0 cm or more.
RESULTS
Patch aneurysmal expansion (mean, 5.4 cm) was detected in eight patients (7.5%). All three women had connective tissue disorders (mean age, 36 years), and all five men had atherosclerotic disease (mean age, 73 years). Five patients were symptom free with their aneurysms detected by surveillance computed tomography scans; two patients had back pain prompting computed tomography scans; and one patient presented with an emergency patch rupture. Aneurysmal patches were successfully revised in three patients. Two patients died in the operating room, and three patch aneurysms (< 5 cm) are still being observed. The mean time to the detection of aneurysmal expansion was 6.5 years after the original operation. Therapy consisted of replacement of a segment of the thoracoabdominal aortic graft and refashioning a smaller patch, including only the visceral artery orifices with separate attachment of the left and possibly right renal artery.
CONCLUSIONS
Although Crawford's inclusion method of visceral patch construction is generally durable, patients undergoing thoracoabdominal aortic replacement require yearly surveillance for the detection of aneurysmal expansion of the visceral patch. We recommend limiting visceral patch size at the original operation by routinely excluding the orifice of the left renal artery. Patients at high risk for recurrent aneurysmal expansion, such as those with connective tissue disorders, will benefit from creating small visceral patches and possibly implanting both renal arteries separately during the original operation. | 10.1067/mva.2001.117149 |
pubmed_428_14806 | Blockade of immunoinhibitory molecules, such as programmed death-1 (PD-1)/PD-ligand 1 (PD-L1), is a promising strategy for reinvigorating exhausted T cells and preventing disease progression in a variety of chronic infections. Application of this therapeutic strategy to cattle requires bovinized chimeric antibody targeting immunoinhibitory molecules. In this study, anti-bovine PD-1 rat-bovine chimeric monoclonal antibody 5D2 (Boch5D2) was constructed with mammalian expression systems, and its biochemical function and antiviral effect were characterized in vitro and in vivo using cattle infected with bovine leukemia virus (BLV). Purified Boch5D2 was capable of detecting bovine PD-1 molecules expressed on cell membranes in flow cytometric analysis. In particular, Biacore analysis determined that the binding affinity of Boch5D2 to bovine PD-1 protein was similar to that of the original anti-bovine PD-1 rat monoclonal antibody 5D2. Boch5D2 was also capable of blocking PD-1/PD-L1 binding at the same level as 5D2. The immunomodulatory and therapeutic effects of Boch5D2 were evaluated by in vivo administration of the antibody to a BLV-infected calf. Inoculated Boch5D2 was sustained in the serum for a longer period. Boch5D2 inoculation resulted in activation of the proliferation of BLV-specific CD4+ T cells and decrease in the proviral load of BLV in the peripheral blood. This study demonstrates that Boch5D2 retains an equivalent biochemical function to that of the original antibody 5D2 and is a candidate therapeutic agent for regulating antiviral immune response in vivo. Clinical efficacy of PD-1/PD-L1 blockade awaits further experimentation with a large number of animals. | 10.3389/fimmu.2017.00650 |
pubmed_569_3636 | BACKGROUND
Compared with conventional laparoscopic surgery, single-incision laparoscopic surgery produces better cosmetic benefits. The aim of this study was to investigate the learning curve for single-incision laparoscopic anterior resection (SILAR) for sigmoid colon cancer using multidimensional methods.
STUDY DESIGN
From September 2009 through May 2014, one hundred and thirteen patients underwent SILAR for sigmoid colon cancer by a single surgeon at Severance Hospital. The learning curve was analyzed using moving average, cumulative sum control chart (CUSUM), and risk-adjusted CUSUM methods. For risk-adjusted CUSUM, surgical failure was defined as conversion to open surgery or conventional laparoscopic surgery, morbidity within 30 days after surgery, <12 harvested lymph nodes, or local recurrence.
RESULTS
Using the moving average method, the peak point for operation time occurred at the 65(th) case (173 minutes). The CUSUM method also showed the operation time peak point at the 65(th) case. However, the risk-adjusted CUSUM curve did not ascend after the 61st case. The operation time and hospital stay for the 60 phase 1 patients (cases 1 to 60) were longer than for 53 phase 2 patients (cases 61 to 113) (166.6 vs 140 minutes; p < 0.001 and 7.1 vs 5.5 days; p = 0.009). Phase 2 patients had a significantly larger tumor diameter and more harvested lymph nodes.
CONCLUSIONS
The learning curve for SILAR for sigmoid colon cancer was 61 to 65 cases according to multidimensional statistical analyses. Single-incision laparoscopic anterior resection is feasible for surgeons experienced in laparoscopic surgery. However, SILAR required more cases for proficiency than the number previously reported for conventional laparoscopic surgery, likely because of its technical challenges. | pubmed_569_3636 |
pubmed_1077_508 | OBJECTIVE
Binaural interaction can be investigated using auditory evoked potentials. A binaural interaction component can be derived from the auditory brainstem response (ABR-BIC) and is considered evidence for binaural interaction at the level of the brainstem. Although click ABR-BIC has been investigated thoroughly, data on 500 Hz tone-burst (TB) ABR-BICs are scarce. In this study, characteristics of click and 500 Hz TB ABR-BICs are described. Furthermore, reliability of both click and 500 Hz TB ABR-BIC are investigated.
METHODS
Eighteen normal hearing young adults (eight women, ten men) were included. ABRs were recorded in response to clicks and 500 Hz TBs. ABR-BICs were derived by subtracting the binaural response from the sum of the monaural responses measured in opposite ears.
RESULTS
Good inter-rater reliability is obtained for both click and 500 Hz TB ABR-BICs. The most reliable peak in click ABR-BIC occurs at a mean latency of 6.06 ms (SD 0.354 ms). Reliable 500 Hz TB ABR-BIC are obtained with a mean latency of 9.47 ms (SD 0.678 ms). Amplitudes are larger for 500 Hz TB ABR-BIC than for clicks.
CONCLUSION
The most reliable peak in click ABR-BIC occurs at the downslope of wave V. Five hundred Hertz TB ABR-BIC is characterized by a broad positivity occurring at the level of wave V.
SIGNIFICANCE
The ABR-BIC is a useful technique to investigate binaural interaction in certain populations. Examples are bilateral hearing aid users, bilateral cochlear implant users and bimodal listeners. The latter refers to the combination of unilateral cochlear implantation and contralateral residual hearing. The majority of these patients have residual hearing in the low frequencies. The current study suggests that 500 Hz TB ABR-BIC may be a suitable technique to assess binaural interaction in this specific population of cochlear implant users. | pubmed_1077_508 |
pubmed_379_19036 | This real-world study compares the outcome of surgery and the sleep-deprivation status of the resident surgeon. Residents who operated the day after a 24-hour on-call period were considered sleep deprived; all other resident surgeons were considered non-sleep-deprived. We retrospectively reviewed data on 6,371 surgical cases and identified 351 postoperative complications. The complication data were analyzed using logistic regression analysis, with outcome being the presence or absence of surgical complications. No statistically significant change in complication incidence was noted when the resident surgeon was sleep deprived. | 10.1097/00007611-199503000-00007 |
pubmed_1096_13072 | BACKGROUND
In patients with penetrating eye injury and a full stomach, suxamethonium is still used for rapid sequence induction of anesthesia. But its use is associated with the rise in intraocular pressure (IOP) and this can result in permanent vision loss in these patients. Dexmedetomidine and clonidine are two alpha-2 adrenergic agonist drugs which prevent the rise in IOP. The aim of this study is to compare the efficacy of intravenous (i.v.) dexmedetomidine and clonidine in preventing an increase in IOP after administration of suxamethonium and tracheal intubation.
MATERIALS AND METHODS
Sixty patients undergoing elective nonophthalmic surgery under general anesthesia were included in this clinical study. Patients were randomly assigned into three groups to receive 0.5 mcg/kg dexmedetomidine (Group D), 2 mcg/kg clonidine (Group C) or normal saline (Group S) as premedication i.v. over a period of 10 min before induction. IOP, heart rate, and mean arterial pressure were recorded before and after premedication, after suxamethonium, after intubation and then after 5 min.
RESULTS
Following administration of dexmedetomidine and clonidine IOP decreased in both groups. After suxamethonium IOP increased in all three groups but it never crossed the baseline in Group D and C. After laryngoscopy and intubation IOP again increased in all three groups but in dexmedetomidine group it never crossed the baseline whereas in clonidine group it was significantly higher than the baseline.
CONCLUSION
Single i.v. dose of dexmedetomidine premedication (0.5 mcg/kg) blunt the IOP and hemodynamic response to suxamethonium injection and tracheal intubation more effectively than single i.v. dose of clonidine premedication (2 mcg/kg). | 10.4103/1658-354X.152878 |
pubmed_255_2732 | Almost thirty years have passed since the surgeon general of the United States released the first report on the effects of smoking (U.S. Department of Health, Education, and Welfare 1964). Over the ensuing years, further reports have expanded our knowledge of the widespread physiological effects of tobacco smoke and those at greatest risk (U.S. Department of Health, Education, and Welfare 1979; U.S. DHHS 1987, 1991, 1992; American Medical Association 1989). Subsequently, there has been a dramatic decrease in the number of smokers; more than thirty-six million Americans have quit smoking since the surgeon general's report (U.S. DHHS 1987, 7). Supporting this trend are the surgeon general's national health objectives for the year 2000 to achieve smoke-free work environments (Koop 1985). All of these trends contribute to current efforts to make hospitals smoke-free environments. | 10.1080/00185868.1993.9950556 |
pubmed_279_780 | A study is presented of 59 patients with macrofocal and transmural myocardial infarction and symptoms of pulmonary edema. It was found that in patients with myocardial infarction complicated by acute left ventricular failure, reduced reserves of autoregulation naniprus is the drug of choice for control of pulmonary edema, particularly, in case of hypokinetic type of cerebral hemodynamics. | pubmed_279_780 |
pubmed_602_17134 | Cigarette smoking impairs glucose tolerance and alters serum levels of hormones involved in glucose metabolism, but the role of nicotine in such hormonal alterations is not well understood. In order to isolate the effects of transdermal nicotine on serum glucose, insulin, growth hormone, and cortisol in smokers, we conducted a randomized double-blind placebo-controlled cross-over study involving 34 healthy volunteer smokers between 18 and 55 years of age. Administration of a 14-mg transdermal nicotine patch resulted in nonsignificantly lowered fasting quantitative insulin-sensitivity index (P =.11) and a nonsignificant 9.3-mg/dL mean increase in serum glucose levels during a 75-g oral glucose tolerance test (OGTT) at time 60 minutes (P =.12). There were no substantial differences between groups in the areas under the curve (AUCs) for glucose (P =.33) or insulin (P =.79) during the OGTT. Levels of insulin and cortisol also were not significantly altered by nicotine. A secondary finding observed in the overall study group (primarily in females) was that nicotine caused a 29% median decrease in serum growth hormone (P =.02). We conclude that nicotine patches may lead to mild hyperglycemia and lowered insulin sensitivity. Further research is needed to determine the clinical implications of the unexpected finding that nicotine decreased growth hormone levels in female smokers. | 10.1016/j.metabol.2003.12.006 |
pubmed_65_715 | OBJECTIVES
To investigate and compare closed and open revision techniques in the treatment of ununited femoral shaft fractures associated with locked nail breakage.
DESIGN
Retrospective.
SETTING
University hospital.
METHODS
Ununited femoral shaft fractures associated with locked nail breakage were treated with either closed or open revision (nine or eighteen cases, respectively). The closed technique entailed closed removal of the broken nail and reinsertion of a stable intramedullary nail after reaming the marrow cavity. The open technique included open removal of the broken nail, reinsertion of a stable intramedullary nail or plate, and cancellous bone graft supplementation. Union rate, union period, perioperative course, and complications were compared.
RESULTS
Eight closed and fifteen open technique cases were followed for at least one year (median two years). Cases treated with the closed technique had a union rate of 100 percent, a union period of 4.4+/-0.9 months, an operating time of 1.5+/-0.4 hours, no blood transfusion, and no complications. Open technique cases demonstrated a union rate of 100 percent, a union period of 5.7+/-1.5 months (p = 0.033), an operating time of 2.4+/-0.4 hours (p < 0.001), blood transfusion of 1,000+/-500 milliliters (p < 0.001), and no complications.
CONCLUSIONS
We recommend the closed revision technique because its union period and operating time are shorter, and it does not require a blood transfusion. Because there is no local wound dissection, infection rates should also be lower. However, the procedure is technically demanding. If it cannot be completed successfully, using the open technique can still achieve a satisfactory outcome. | 10.1097/00005131-199909000-00006 |
pubmed_813_3583 | Pancreatic and duodenal homeobox gene-1 (PDX-1) is a transcription factor which regulates the insulin gene expression. In this study, we tried to elucidate the role of PDX-1 in the glucose-induced transcriptional activation of the human insulin gene promoter in MIN6 cells. Electrophoretic mobility shift assay (EMSA) and chloramphenicol acetyltransferase (CAT) assay demonstrated that both DNA-binding activity and transcriptional activity of PDX-1 were increased with 20 mmol/l glucose more than with 2 mmol/l glucose. The DNA-binding activity of PDX-1 induced by high glucose was blocked by phosphatase treatment, suggesting the involvement of PDX-1 phosphorylation in this event. In an in vitro phosphorylation study, PDX-1 was phosphorylated by protein kinase C (PKC), but not by cAMP dependent protein kinase (PKA) or mitogen-activated protein kinase (MAPK). Furthermore, increased PDX-1 function induced by high glucose was blocked by calphostin C, an inhibitor of all PKC isoforms, but unaffected by phorbol 12-myristate 13-acetate (PMA), an activator of classical and novel PKC, or Gö 6976, an inhibitor of classical and novel PKC, which suggested that the PKC family which activated PDX-1 in MIN6 cells was atypical PKC. Western blot and immunocytochemical studies with anti-PKC zeta antibody confirmed the presence of PKC zeta, one of the isoforms of atypical PKC, in MIN6 cells. Furthermore, PKC zeta activity was significantly increased by glucose stimulation. These results suggest that high glucose increased DNA-binding activity of PDX-1 by activating atypical PKC including PKC zeta, resulting in transcriptional activation of the human insulin gene promoter. | 10.1507/endocrj.46.43 |
pubmed_348_19971 | BACKGROUND
Evidence suggests that people who are more responsive to psychological stress are at an increased risk of developing obesity. However, the biological mechanisms underlying this phenomenon are poorly understood. The cytokines leptin, interleukin-1 receptor antagonist (IL-1Ra) and interleukin-6 (IL-6) play a key role in fat metabolism and abnormal circulating levels of these proteins have been reported in obese people and in individuals subject to stress.
OBJECTIVE
This study investigated whether cytokine responses to acute mental stress are associated with adiposity in healthy young women.
DESIGN AND SUBJECTS
A laboratory study of 67 women, aged 18-25 years, recruited from University College London.
MEASUREMENTS
Height, weight and waist circumference were measured and body fat mass was estimated by bioelectrical impedance body composition analysis. Laboratory mental stress testing was carried out and blood pressure and heart rate were recorded at baseline, during two moderately challenging tasks (Stroop and speech) and during recovery 40-45 min post-stress. Blood samples taken at baseline, immediately post-stress and 45 min post-stress, were used for assessment of circulating cytokines. Saliva samples taken throughout the session were assessed for cortisol.
RESULTS
Women who had larger cytokine responses to stress were more abdominally obese than women with smaller cytokine stress responses. Specifically, there was a positive correlation between waist circumference and stress-induced increases in plasma levels of leptin (r=0.35, P<0.05) and IL-1Ra responses (r=0.29, P<0.05). There was also a significant positive correlation between prolonged diastolic blood pressure responses to stress and measures of total and abdominal obesity (r=0.28-0.33, P<0.05).
CONCLUSION
Increased cytokine production could be a mechanism linking stress and abdominal obesity. | 10.1038/sj.ijo.0803767 |
pubmed_143_2675 | Interleukin (IL)-15 is an essential immune-modulator with high potential for use in cancer treatment. Natural IL-15 has a low biological potency because of its short half-life and difficulties in mass-production. IL-15Rα, a member of the IL-15 receptor complex, is famous for its high affinity to IL-15 and its ability to lengthen the half-life of IL-15. We have double-transfected IL-15 and its truncated receptor IL-15Rα into CT26 colon cancer cells to target them for intracellular assembly. The secreted IL-15:IL-15Rα complexes were confirmed in ELISA and Co-IP experiments. IL-15:IL15Rα secreting clones showed a higher anti-tumor effect than IL-15 secreting clones. Furthermore, we also evaluated the vaccine and therapeutic efficacy of the whole cancercell vaccine using mitomycin C (MMC)-treated IL-15:IL15Rα secreting CT26 clones. Three sets of experiments were evaluated; (1) therapeutics, (2) vaccination, and (3) longterm protection. Wild-type CT26-bearing mice treated with a single dose of MMC-inactivated secreted IL-15:IL-15Rα clones prolonged survival compared to the control group. Survival of MMC-inactivated IL-15:IL-15Rα clone-vaccinated mice (without any further adjuvant) exceeded up to 100%. This protection effect even lasted for at least three months after the immunization. Secreted IL-15:IL-15Rα clones challenging trigger anti-tumor response via CD4+ T, CD8+ T, and natural killer (NK) cell-dependent cytotoxicity. Our result suggested that cell-based vaccine secreting IL-15:IL-15Rα, may offer the new tools for immunotherapy to treat cancer. | 10.14348/molcells.2019.0188 |
pubmed_1000_7209 | Insulin is largely secreted as serial secretory bursts superimposed on basal release, insulin secretion is regulated through changes of pulse mass and frequency, and the insulin release pattern affects insulin action. Coordinate insulin release is preserved in the isolated perfused pancreas, suggesting intrapancreatic coordination. However, occurrence of glucose concentration oscillations may influence the process in vivo, as it does for ultradian oscillations. To determine if rapid pulsatile insulin release may be induced by minimal glucose infusions and to define the necessary glucose quantity, we studied six healthy individuals during brief repetitive glucose infusions of 6 and 2 mg x kg(-1) x min(-1) for 1 min every 10 min. The higher dose completely synchronized pulsatile insulin release at modest plasma glucose changes ( approximately 0.3 mM = approximately 5%), with large ( approximately 100%) amplitude insulin pulses at every single glucose induction (n = 54) at a lag time of 2 min (P < 0.05), compared with small (10%) and rare (n = 3) uninduced insulin excursions. The smaller glucose dose induced insulin pulses at lower significance levels and with considerable breakthrough insulin release. Periodicity shift from either 7- to 12-min or from 12- to 7-min intervals between consecutive glucose (6 mg x kg(-1) x min(-1)) infusions in six volunteers revealed rapid frequency changes. The orderliness of insulin release as estimated by approximate entropy (1.459 +/- 0.009 vs. 1.549 +/- 0.027, P = 0.016) was significantly improved by glucose pulse induction (n = 6; 6 mg x kg(-1) x min(-1)) compared with unstimulated insulin profiles (n = 7). We conclude that rapid in vivo oscillations in glucose may be an important regulator of pulsatile insulin secretion in humans and that the use of an intermittent pulsed glucose induction to evoke defined and recurrent insulin secretory signals may be a useful tool to unveil more subtle defects in beta-cell glucose sensitivity. | 10.1152/ajpendo.2000.278.1.E162 |
pubmed_741_495 | A method is presented for the quantitative estimation of the individual amino acid radioactivity in biological samples. The material is deproteinized with cold acetone, and, after acetone evaporation, is passed through a column containing 1 g of Amberlite XAD-2, then eluted with 10% ethanol. The samples are derivatized with Sanger's reagent (alkaline 1-fluoro-2,4-dinitrobenzene) and passed again through the Amberlite XAD-2 column; the 10% ethanol eluate is now discarded and the DNP-amino acids eluted with acetone. Aliquots are used for TLC chromatography on Silicagel plates; the spots are identified, cut away and their radioactivity estimated. The actual recovery of radioactivity in the spots is about 86-92% of the initial radioactivity. No contamination with radioactive glucose, lactate, pyruvate or glycerol has been observed. | 10.1016/0165-022x(83)90022-2 |
pubmed_234_2153 | Since the discovery that the therapeutic efficacy of antipsychotic drugs was significantly correlated to their ability to block dopamine D2 receptors, abnormal dopamine transmission in the forebrain has been postulated to underlie psychosis in schizophrenia. In the past 15 years, an impressive amount of clinical and basic research aimed at the study of schizophrenia has indicated that prefrontal and temporal cortical abnormalities may be more important in the etiology of many of the symptoms of schizophrenia, including psychosis. However, the cortical systems that appear to have structural and/or metabolic abnormalities in schizophrenia patients potently regulate forebrain dopamine transmission through a number of mechanisms. In turn, dopamine modulates excitatory transmission mediated by frontal and temporal cortical projections to the basal ganglia and other regions. The present review summarizes the multiple interactions between forebrain DA systems and frontal and temporal corticostriatal transmission. It then examines the role of these interactions in normal behaviors and the psychopathology of schizophrenia. | 10.1016/s0006-3223(99)00078-5 |
pubmed_49_8946 | We carried out experiments in urethan-anesthetized rats to determine 1) whether increasing the activity of small groups of neurons in the caudal ventrolateral medulla (CVLM) by injecting picomoles of an excitatory amino acid altered cardiovascular and/or respiratory homeostasis and 2) whether the depressor responses after chemical excitation in the CVLM were elicited only from the immunohistochemically identified catecholamine-containing cell group. In discrete sites in the CVLM, unilateral injections of 1-12 nl (20-240 pmol) of DL-homocysteic acid (DLH; 20 mM, pH 7.4) selectively or concomitantly inhibited arterial pressure, heart rate, and diaphragm electromyogram (EMG) activity. In the region in which chemical excitation slowed breathing, units were recorded extracellularly that discharged with respiratory periodicity. Sites where the smallest volumes of DLH decreased arterial pressure were located outside the immunohistochemically identified DBH-positive cell bodies. These data suggest that either the same or neighboring neurons in the CVLM are involved in the central neural circuitry for both cardiovascular and respiratory control and that cells other than the catecholaminergic cell group are important in medullary depressor responses. | 10.1152/ajpheart.1989.256.3.H688 |
pubmed_520_15387 | Von Willebrand disease (VWD) is an inherited bleeding disorder caused by quantitative or qualitative deficiencies in von Willebrand factor (VWF). People with VWD may experience excessive, recurrent or prolonged bleeding, particularly during menstruation, childbirth, surgery or following trauma. However, many VWD patients are undiagnosed, and therefore inadequately treated. Reasons for the underdiagnosis of VWD include its relatively mild symptoms, complex diagnosis, lack of awareness among non-specialist healthcare providers and the general population, and a lack of prioritisation of disorders disproportionately affecting females. The vwdtest.com platform was launched as part of a global initiative to raise awareness and improve diagnosis of VWD. Besides providing VWD-specific educational resources, the website includes an online bleeding self-assessment tool and offers diagnostic support for individuals, and their providers, who have a score suggestive of a bleeding disorder. vwdtest.com helps to address these unmet needs, especially in regions with limited access to educational and diagnostic resources. | 10.1016/j.blre.2022.101018 |
pubmed_892_18200 | Arterial stenoses and luminal-surface irregularities at anastomoses cause blood-flow disturbances with slow recirculation. The authors created a computer simulation to study the rates of the release into blood of atherogenic substances such as low-density lipoproteins and their breakdown products from within the arterial walls at stenoses. Finite-difference methods were used to solve the Navier-Stokes equations (in the form of stream function and vorticity function) and the steady-state mass transfer equation for bell-shaped stenoses with two different degrees of constriction. This simulation indicated that the efflux rates of lipids and their breakdown products from the vessel walls were suppressed in the region of disturbed flow, with slow circulation distal to stenoses. The lowest efflux rate was found at the point of flow separation, and this rate was much lower than rates in regions of undisturbed flow. Therefore, this mathematical model predicts that locally disturbed blood flow at arterial stenoses and arterial anastomoses is responsible for two distinct phenomena: first, it provides favourable conditions for lipid infiltration into vessel walls; and, second, it impairs the release into the blood of atherogenic substances accumulated in the vessel wall. Such mass transfer abnormalities may account for atherogenesis and the late failures of arterial reconstructions at these sites. | pubmed_892_18200 |
pubmed_926_18863 | As informal sperm donation becomes more prevalent worldwide, understanding donor psychology and interactions is critical in providing effective policy, equitable legislative frameworks and frontline health support to an ever-growing number of global participants. We analyse data of informal sperm donors who were members of the connection website PrideAngel to identify the role and effect of several factors, e.g. kinship, social networks, personality, and risk perception, on behaviour. A key strength of the study is the ability to analyse various factors, such as the level and history of informal donation, risk concerns, number of women to whom donations are informally made and the number of offspring. Our results indicate donors who have also been active in formal clinical settings (compared with those who exclusively donate informally), donate to more women in the informal market and realise more offspring. Donor's sexual orientation also affects activity. From a personality perspective, conscientiousness provides comparative advantage. It is possible this characteristic provides positive externalities, as more conscientious men may be more efficient or organised in a market that requires increased cooperation and communication. The importance of kin and social networks seems to affect frequency of donation only, possibly representing a time constraint (or opportunity cost). | 10.1016/j.rbmo.2017.08.023 |
pubmed_377_12688 | General action and inaction concepts have been shown to produce broad, goal-mediated effects on cognitive and motor activity irrespective of the type of activity. The current research tested a model in which action and inaction goals interact with the valence of incidental moods to guide behavior. Over four experiments, participants' moods were manipulated to be positive (happy), neutral, or negative (angry or sad), and then general action, inaction, and neutral concepts were primed. In Experiment 1, action primes increased intellectual performance when participants experienced a positive (happy) or neutral mood, whereas inaction primes increased performance when participants experienced a negative (angry) mood. Including a control-prime condition, Experiments 2 and 3 replicated these results measuring the number of general interest articles participants were willing to read and participants' memory for pictures of celebrities. Experiment 4 replicated the results comparing happiness with sadness and suggested that the effect of the prime's adoption was automatic. Overall, the findings supported an interactive model by which action concepts and positive affect produce the same increases in active behavior as inaction concepts and negative affect. | 10.1037/a0024130 |
pubmed_1044_16228 | OBJECTIVE
To define liquid chromatography tandem mass spectrometry (LC-MS/MS)-based cutoff levels and panels of steroid hormones, to improve diagnosis of nonclassic congenital adrenal hyperplasia (NCCAH) and other partial enzyme defects in the adrenals.
DESIGN
Prospective cohort analysis.
SETTING
University hospital-based tertiary endocrine center.
PATIENTS
One hundred and twenty-one healthy adults and 65 patients evaluated for possible NCCAH (validation cohort).
INTERVENTIONS
The LC-MS/MS-determined cutoffs for 11 steroids (basal and cosyntropin-stimulated) were defined by 2.5% and 97.5% percentile in healthy subjects. Validation cohort was used for comparison.
MAIN OUTCOME MEASURES
Percentage of patients diagnosed with NCCAH among patients with polycystic ovary syndrome (PCOS)-like symptomatology. Evaluation of the defined LC-MS/MS-based cutoff levels for steroid hormones among this patient group.
RESULTS
Of the 65 PCOS-like patients evaluated for possible NCCAH, 8 (12.5%) were discovered and genetically verified, and 2 had classic congenital adrenal hyperplasia. Cosyntropin-stimulated 17-hydroxyprogesterone (17OHP) showed the best diagnostic accuracy for NCCAH with an area under the curve of 0.95 (0.89-1.0 with a sensitivity of 86% and a specificity of 88%. In homozygote patients, 21-deoxycortisol and 17OHP levels were elevated, in heterozygote patients only 17OHP (basal or stimulated) was raised. Four healthy patients in the validation cohort had 17OHP above the basal cutoff.
CONCLUSIONS
The NCCAH syndrome is frequent in patients with suspected PCOS, and should be considered as a routine screening when assessing infertility. We suggest the use of serum steroid profiling, including 21-deoxycortisol, together with the cosyntropin stimulation test with 17OHP. Our data support a 17OHP cutoff of 8.5 nmol/L (2.8 ng/mL) 60 minutes after cosyntropin stimulation, when measured with LC-MS/MS, significantly lower than current European guidelines.
CLINICAL TRIALS NUMBER
NCT0218660. | 10.1016/j.fertnstert.2022.05.012 |
pubmed_1090_13514 | The reliability of the notion that pedophilia is caused by sexual abuse in childhood was explored by examining retrospective self-reports of 344 males. Included in the study were 77 heterosexual pedophiles, 54 homosexual pedophiles, 51 nonpedophilic sex offenders against children, 36 sex offenders against physically mature females, 75 heterosexual paid volunteers who erotically preferred mature females, and 51 homosexual clients who preferred mature males. For each sex offender the differential diagnosis of an erotic preference for minors vs. a preference for physically mature partners was made by means of the phallometric test of erotic gender and age preferences. The analysis of self-reports confirmed that the proportion of pedophiles who report having been sexually abused in childhood by mature persons is larger than that of men who were not charged for or accused of a sex offense against a child though the difference is relatively small (28.6 vs. 13.9 and 10.7% for the heterosexual pedophiles and the two groups of gynephiles, respectively, and 25.9 vs. 11.8% for the homosexual pedophiles and androphiles, respectively). Further analysis demonstrated, however, that pedophiles who admitted having an erotic interest in children significantly more often claimed that they had been sexually abused as children than pedophiles who did not admit having such feelings. This interdependence renders the reliability of these self-reports questionable. | 10.1007/BF01542465 |
pubmed_515_19386 | Hydro-distilled essential oils from Acorus calamus rhizomes collected from six different geographical zones in the northwest Himalayan region of Uttarakhand have been analyzed by GC and GC/MS. All the oils differed in their qualitative and quantitative make up, although beta-asarone was the major constituent of all of them. The essential oils and the isolated beta-asarone were screened for anthelmintic activity using contractility of Ascaridia galli. beta-Asarone, in particular, showed potent activity with IC50 values of 75.4 +/- 61.8 ng/mL. | pubmed_515_19386 |
pubmed_520_8579 | Cardiovascular diseases (CVDs) remain one of the leading causes of death with an estimated 17.9 million lives lost each year. Circulating high levels of low-density lipoproteins (LDL), are susceptible to various modifications such as oxidation and glycosylation (diabetics). This leads to development of atherosclerosis, which can impair quality of life and death. There is a growing need for detection and subsequent treatment of high LDL cholesterol, which could be achieved through design of a system for detection of LDL with subsequent drug release for disease management. Fenofibrate-loaded solid lipid nanoparticles (SLNs) were synthesized and coated with anti-oxidized LDL antibodies to form anti-LDL SLN. The nanoparticles were delivered via an osmotic pump delivery device implanted on the jugular vein of Large White pigs as an anti-LDL theranostic system, referred to as an Intra-Vascular Implantable Sensor and Drug Delivery Device (IVISDDD), for modulation of systemic LDL cholesterol levels. Modulatory fenofibrate release was observed from the IVISDDD following in vivo analysis in response to anti-LDL SLN-LDL complex uptake and degradation. This notably contributed to a 29.9% reduction in total cholesterol via a 37.4% reduction in LDL levels, and an increase in HDL levels. The observed effect on cholesterol levels indicated that the device could be employed for detection of circulating biomarkers and delivery of lipophilic drugs in CVDs. | 10.1016/j.ijpharm.2022.122258 |
pubmed_647_1300 | Evaluation has been made of the distribution of hard scales containing naturally occurring radioactive materials (NORM) in a range of oilfield equipment in Syrian oilfields. One hundred and fifty-two scale samples from oilfield equipment were collected and analysed for radioactivity, elemental and mineralogical compositions. The average 226Ra, 228Ra and 224Ra concentrations in scales were found to be 174, 91 and 67 Bqg(-1), respectively; the highest value of 226Ra was found to be 1520 Bqg(-1). A gradual increase in 226Ra specific activity from down-hole tubulars to surface parts of the installations was observed. The 228Ra/226Ra mean activity ratio was observed to be 0.76, indicating a Th/U mass ratio of about 2.3. This value can be considered a fingerprint for the Th/U mass ratio of the geological formation of the reservoir. Radium isotopic data were also used to estimate the age of the deposited scales using the 224Ra/228Ra activity ratio; the highest average age (5.3 years) was found to be in scales collected from valves. Multiple regressions of the data have shown that 226Ra is more highly correlated with Ba and Sr content in scales (R2=0.92) than Ca. Around 77% of 226Ra was found to be incorporated with anhydrate barium strontium sulphate (R2=0.93), solubility in water being very low to negligible; lower levels of radium isotopes were found in calcite. | 10.1016/j.apradiso.2005.05.050 |
pubmed_980_17200 | Mitochondria are double membrane-bound organelles which are essential for the viability of eukaryotic cells, because they play a crucial role in bioenergetics, metabolism and signaling [...]. | 10.3390/ijms22010001 |
pubmed_839_17625 | BACKGROUND
Patterns of symptom frequency and distress have not been examined long-term after heart transplantation, nor have predictors of long-term symptom frequency and distress. This report identified the most commonly reported and distressful symptoms long-term after transplantation, described patterns of symptom frequency and distress over time, and examined predictors of symptom frequency and distress at 5 and 10 years after heart transplantation.
METHODS
The sample included 555 participants from a prospective, multisite, longitudinal study of quality of life outcomes. Patients were 78% male, 88% white, 79% married, and mean age of 54 years at time of heart transplantation. Data were collected using patient self-report and medical records review. Statistical analyses included descriptive statistics, Pearson correlations, t-tests, and generalized linear models.
RESULTS
Significant predictors of lower symptom frequency after heart transplantation were not having psychological problems and not having cardiac allograft vasculopathy at 5 years, and not having psychological problems and not having infection at 10 years. Significant predictors of less symptom distress were having more than a high school education, having no psychological problems, and having gout at 5 years, and being married at 10 years.
CONCLUSIONS
Symptom frequency is low and symptom distress is moderate long-term after heart transplantation. Significant relationships exist between both demographic and clinical variables and symptom frequency and distress. Identification of the most common and bothersome symptoms after heart transplantation provides clinicians with important information from which to develop a plan of care. | 10.1016/j.healun.2009.04.020 |
pubmed_490_18596 | BACKGROUND
Direct brain stimulation via electrodes implanted for intracranial electroencephalography (iEEG) permits the modulation of endogenous electrical signals with significantly greater spatial and temporal specificity than non-invasive approaches. It also allows for the stimulation of deep brain structures important to memory, such as the hippocampus, that are difficult, if not impossible, to target non-invasively. Direct stimulation studies of these deep memory structures, though, have produced mixed results, with some reporting improvement, some impairment, and others, no consistent changes.
OBJECTIVE/HYPOTHESIS
We hypothesize that to modulate cognitive function using brain stimulation, it is essential to modulate connected nodes comprising a network, rather than just alter local activity.
METHODS
iEEG data collected while patients performed a spatiotemporal memory retrieval task were used to map frequency-specific, coherent oscillatory activity between different brain regions associated with successful memory retrieval. We used these to identify two target nodes that exhibited selectively stronger coupling for spatial vs. temporal retrieval. In a subsequent session, electrical stimulation - theta-bursts with a fixed phase-lag (0° or 180°) - was applied to the two target regions while patients performed spatiotemporal retrieval.
RESULTS
Stimulation selectively impaired spatial retrieval while not affecting temporal retrieval, and this selective impairment was associated with theta decoupling of the spatial retrieval network.
CONCLUSION
These findings suggest that stimulating tightly connected nodes in a functional network at the appropriate phase-lag may effectively modulate the network function, and while in this case it impaired memory processes, it sets a foundation for further network-based perturbation studies. | 10.1016/j.brs.2017.09.016 |
pubmed_576_15933 | CABG patients have unique anatomical and physiological causes for postoperative pain that provide the critical care nurse with the challenge of identifying the most effective interventions for pain control. This article analyzes research reports on non-pharmacologic pain control for CABG patients and recommends state-of-the-art nursing interventions based on this body of research. | 10.1097/00003465-199311000-00005 |
pubmed_712_10812 | The inhalational anesthetics reversibly inhibit mitochondrial electron transport from NADH-linded substrates at the level of the enzyme NADH-dehydrogenase. The effect of this inhibition on ATP production is probably not the basis of the anesthetic state, as the level of high-energy phosphate in the brain does not decrease during anesthesia. Anesthetics, therefore, interfere with brain energy untilization, in addition to brain energy production. Inhibition by anesthetics of mitochondrial calcium uptake, which results from the inhibition of electron transport, may be an important anesthetic effect if it raises the intracellular calcium level. Other areas of investigation which have not been discussed here include the effects of anesthetics on glycolytic and other enzyme systems, ion fluxes, neurotransmitter synthesis and release, and on the structure of natural and artificial membranes. It is now appreciated that most of the inhalational anesthetics are metabolized by the endoplasmic reticulum of hepatocytes. The biotransformation of several anesthetics can be increased by drugs which induce hepatic microsomal enzymes. The organ toxicities of chloroform, trichloroethylene, fluroxene, methoxyflurane, and possibly of halothane and enflurane are related to their intermediary or final metabolites. It is of anesthetic drugs for an individual patient. | 10.1016/s0039-6109(16)40683-3 |
pubmed_459_5752 | Signal transfer in the isolated frog muscle spindle is investigated using the linear frequency domain analysis technique. Sinusoidal stretches of different amplitudes (20-120 micron) and frequencies (0.1-120 Hz) were applied at different levels of static prestretch, ranging from resting length (L0) up to L0 + 400 micron, so that the frequency-response characteristics were measured at different operating points within the dynamic range. The neuronal responses were recorded from the first node of the afferent stem fiber with a modified air-gap technique. By this means, subthreshold receptor potentials, prepotentials preceding the impulse, and the propagated action potentials were recorded simultaneously, thus providing a detailed insight into the encoding process. There is a well-defined dynamic range of receptor responses. At L0, the encoding site is depolarized to its firing level and discharges spontaneous stimulus-independent impulses. The upper limit is given by the saturation of the receptor potential, which keeps the depolarization maximum below the level of sodium inactivation. Therefore a "depolarization block" or "overstretch" does not exist in the muscle spindle; i.e., the receptor retains its ability to encode information over a large range of dynamic and static displacements. Since the dynamic curves of the receptor potential are not symmetrical about their static operating point, the impulse pattern remains modulated throughout the dynamic range, even if small sinusoids are superimposed on a large static prestretch. The afferent discharge pattern is mainly regulated by the modulated AC component of the receptor potential. At low stimulus frequencies (less than 1 Hz) the receptor potential modulates almost linearly about the mean membrane voltage, so that the evoked discharge pattern displays a smooth analog signal, which is close to sinusoidal. Increasing the static prestretch increases both the peak response and the modulation depth of the impulse pattern. In the intermediate frequency range (1-10 Hz), the cycle histogram disintegrates into discrete peaks separated by empty bins, because the nonlinear receptor potential elicites firmly phase-locked action potentials during its fast depolarization transient. Raising the prestretch level improves the precision of phase locking and increases the number of spikes elicited per cycle.(ABSTRACT TRUNCATED AT 400 WORDS) | 10.1152/jn.1985.53.1.76 |
pubmed_188_4005 | There is increasing evidence indicating that peptidylprolyl cis/trans isomerase, NIMA-interacting 1 (Pin1) plays a decisive role in a variety of cancers. Nevertheless, its function in laryngeal squamous cell carcinoma (LSCC) has not been elaborated. The aim of this study is to determine the role of Pin1 in LSCC. Here, we established stably transfected Hep-2 cells with low expression of Pin1. Intriguingly, cell proliferation, migration, and invasion was significantly inhibited in Pin1-silenced Hep-2 cells. Similarly, knockdown of Pin1 induced apoptosis of Hep-2 cells, as evidenced by increased expression of cleaved-caspase-3, cleaved-PARP, and bax, and decreased expression of bcl2. We also demonstrated that silencing of Pin1 down-regulated β-catenin and cyclin D1 expression. Inversely, over-expression of β-catenin reversed the inhibiting effect of Pin1 silencing on Hep-2 cells. Moreover, we proved that knockdown of Pin1 inhibited tumorigenesis of Hep-2 cells in vivo. Taken together, we demonstrate that silencing of Pin1 effectively suppresses the growth of Hep-2 cells through β-catenin, indicating that Pin1 possess the potential to serve as a therapeutic target for the treatment of LSCC. | 10.1139/bcb-2017-0334 |
pubmed_710_15570 | Advances in imaging and technique have pushed the boundaries of the types of surgical interventions available to fetuses with congenital and developmental abnormalities. This review focuses on fundamental aspects of fetal anesthesia, including the physiologic changes of pregnancy, uteroplacental perfusion, and fetal physiology. We discuss the types of fetal surgeries and procedures currently being performed and discuss the specific anesthetic approaches to different categories of fetal surgeries. We also discuss ethical aspects of fetal surgery and anesthesia. | 10.1016/j.clp.2019.08.011 |
pubmed_1104_13881 | Important declines in the diagnosis of schizophrenia have been demonstrated in different countries and continents over the past few decades. Is still not clear if this findings reflects a true decrease in the incidence or is simply an artefact. The administrative rates are influenced by factors such as changes in the illness behavior of the patients, changes in diagnostic habits, administrative inaccuracies, changes in the organisation and delivery of psychiatric services, or changes the underlying pupulation structure. | pubmed_1104_13881 |
pubmed_222_8917 | The heterotrimeric Sec61p complex is a key component of the protein translocation apparatus of the endoplasmic reticulum membrane. The complex characterized from yeast includes Sec61p, a 10-transmembrane-domain membrane protein which has a direct interaction with Sss1p, a small C-terminal anchor protein. In order to gain some insight into the architecture of this complex we have functionally expressed Sec61p as complementary N- and C-terminal fragments. Chemical crosslinking of Sss1p to specific Sec61p fragments in these functional combinations and suppression of sec61 mutants by over-expression of Sss1p have led to identification of the region which includes transmembrane domains TM6, TM7 and TM8 (amino acid residues L232-R406) of Sec61p as a major site of interaction with Sss1p. | 10.1093/emboj/16.15.4549 |
pubmed_281_10132 | Inguinal hernias are typically classified based on their location and can be divided into two types. The most commonly seen inguinal hernias are direct and indirect, which can both potentially require surgical intervention. When both types of hernias are seen simultaneously, it is classified as a pantaloon hernia. This case describes an instance of a femoral hernia being found along with a pantaloon hernia. We present a case of what was projected to be a common inguinal hernia repair but progressed to a rare presentation of a femoral hernia superimposed on a pantaloon hernia. Pantaloon hernias plus a femoral hernia is a rare defect that does not present as often as the different types of isolated hernias. | 10.1093/jscr/rjac514 |
pubmed_56_20063 | Exposure of the mitral valve can be challenging using conventional sternotomy and thoracotomy incisions in patients with pectus deformity. We report the use of a robotic approach to replace a rheumatic mitral valve in a patient with pectus excavatum. doi: 10.1111/jocs.12740 (J Card Surg 2016;31:306-308). | 10.1111/jocs.12740 |
pubmed_964_10184 | Factory workers caught in machinery and construction workers falling or struck by huge beams are images that typically come to mind when considering serious hazards in the workplace. But these types of events account for only a small portion of job-related fatalities each year. Transportation-related fatalities, along with assaults and violent acts during work, made up almost two-thirds of the 6,588 fatal work injuries recorded in 1994. The majority of job-related fatal work events occurred on the streets and highways and in public buildings and in areas such as grocery stores and parking lots. Today the most deadly jobs are found in outdoor occupations such as fishing and timber cutting. In fact, in all 10 jobs studied that have high fatality rates, most workers are affected by severe weather conditions while driving on highways, performing farm chores and working at construction sites. Highway crashes are the primary cause of trucker fatalities; falls are the leading cause of death for roofers, construction laborers and structural metal workers, while tractor rollovers account for a third of farm worker fatalities. Another deadly contributing factor for some workers is homicide, which accounted for 16 percent of job-related fatalities in 1994. Workers most at risk are those who work alone, work late at night and handle varying sums of money. Taxicab drivers are the most susceptible and have a work injury fatality rate nine times higher than the national rate of 5 deaths per 100,000 workers. Others at high risk of homicide include gas station cashiers, grocery store employees and workers in retail eating and drinking establishments. Although the risk of a fatal injury at work varies greatly by occupation and industry, no one is immune. For prevention, workers and employers need to know what jobs are risky, what equipment is dangerous and what activities are hazardous. They also should understand that a fatal incident can happen to anyone. | pubmed_964_10184 |
pubmed_978_7791 | The relationship between hypothalamic temperature and deep interscapular temperature measured just below the brown fat lobes has been studied during desynchronized sleep at two ambient temperatures (24 degrees C and 4 degrees C) before and after adaptation (9 days) to cold (4 degrees C). The results show that the increase in hypothalamic temperature during this stage of sleep occurs independently of a transfer of heat from interscapular brown fat. | pubmed_978_7791 |
pubmed_14_10224 | Sjogren-Larsson Syndrome is a rare autosomal disorder which occurs with 100% penetrance and is classically characterized by ichthyosis, spasticity and mental handicap. This has rarely been described in people of Indian origin, case reports mainly being restricted to Caucasians. We have described a 6-year-old girl with classical features of this syndrome, the symptoms having started in infancy. The spasticity is mainly diplegic in nature. Skin changes of ichthyosis are generalized and more in the flexural areas. Mental retardation is severe. Management is supportive. | 10.1007/BF02859387 |
pubmed_259_136 | Lysophosphatidylcholine (LPC) is an endogenous phospholipid released from the cell membrane during ischemia, and it has potent, local effects on cardiac tissues. LPC has been implicated in arrhythmogenesis during ischemia by increasing intracellular Ca2+. However, it is not known whether LPC influences atrial release of atrial natriuretic peptide (ANP). The aim of this study was to investigate the effect of LPC on ANP secretion from isolated, perfused, beating rat atria. LPC (10 and 30 micromol/L) caused decreases in ANP secretion in a dose-dependent manner, with slight increases in intra-atrial pressure and extracellular fluid (ECF) translocation. Therefore, the ANP secretion in terms of ECF translocation was markedly decreased by LPC. The order of the suppressive effect of ANP release was stearoyl-LPC>LPC>myristoyl-LPC=lauroyl-LPC. Staurosporine and wortmannin significantly attenuated suppression of the ANP release and an increase in intra-atrial pressure by LPC. High extracellular Mg2+ also attenuated the LPC-induced suppression of ANP release. However, other protein kinase C inhibitors such as chelerythrine, GF 109203X, and tamoxifen citrate did not affect LPC-induced suppression of ANP release. In single atrial myocytes, LPC caused increases in intracellular Ca2+ in a dose-dependent manner. The order of an increase in intracellular Ca2+ by LPC was stearoyl-LPC>LPC>myristoyl-LPC=lauroyl-LPC. An increase in intracellular Ca2+ by LPC was attenuated by staurosporine. These results suggest that LPC-induced suppression of ANP release through protein kinase C/Ca2+ and phosphoinositol-3-kinase might in part play an important role in the development of hypertension. | 10.1161/01.HYP.0000071317.98004.B3 |
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