Analysis of morbid events and risk factors for death after cardiac transplantation.
Risk factors for death after cardiac transplantation performed at the University of Alabama at Birmingham from January 1981 to July 1985 included (by multivariate analysis) higher calculated preoperative pulmonary vascular resistance (early and constant phases), morphology of cardiomyopathy (versus ischemic heart disease) (constant phase only) and black race (constant phase). Overall actuarial survival was 71% at 1 year and 48% at 3 years (including azathioprine and cyclosporine eras). The hazard function for death was highest immediately after operation and declined rapidly thereafter, merging with a constant phase of risk at about 3 months. The most favorable group for long-term survival was the group of white patients with ischemic heart disease and low pulmonary vascular resistance. When such patients had a pulmonary vascular resistance less than 3 units.m2, the 3 year survival rate exceeded 85%. The most common causes of death were acute rejection (24%) and infection (17%). The risk of infection remained highest during the first several months after any period of augmented immunosuppression.


Effects of laparoscopy on surgical discharge practice patterns.
The length of stay (LOS) after surgical procedures often varies regionally and reflects local idiosyncratic practice patterns. We sought to elicit the influence of local pressures (in the form of the technologic imperative exerted by laparoscopy) on discharge physician practice style as measured by LOS. Patients undergoing prostatectomy, nephrectomy, and hysterectomy in 2003 were identified from the Nationwide Inpatient Sample using the International Classification of Diseases, Ninth Revision, codes. Within each procedure, the laparoscopy volume was measured and sorted into tertiles. Patients remaining in the hospital longer than the 90th percentile after each surgery were excluded to minimize the influence of imperative indications on LOS. For each procedure, generalized linear models were used to measure the relationship between the hospital laparoscopy volume and log-transformed LOS outcomes among patients undergoing conventional surgery. In 2003, 2%, 19%, and 16% of patients underwent laparoscopic prostatectomy, nephrectomy, and hysterectomy, respectively. A hospital's laparoscopy and conventional volumes were moderately to highly correlated for hysterectomy (r = 0.65) and nephrectomy (r = 0.58) and less so for prostatectomy (r = 0.24). Among patients undergoing conventional prostatectomy and nephrectomy, those treated at high-volume laparoscopy hospitals had 0.41 and 0.30 fewer hospital days, respectively, compared with those treated at hospitals at which only conventional surgery was performed (both P <0.05). This effect was partially explained by a hospital's open procedure volume (both P = 0.07). Similar relationships were not evident for hysterectomy. These data highlight that patients treated by conventional methods at high-volume laparoscopy centers have shorter hospital stays and suggest that physician practices might susceptible to external influences such as the technologic imperative.


Enhanced recovery after surgery in patients undergoing craniotomy: A meta-analysis.
Enhanced recovery after surgery (ERAS) is a multidisciplinary,and evidence-based perioperative care method. It is effective in shortening hospital stays and improving clinical outcomes. However, the application of ERAS in craniotomy lacks reliable evidence. The purpose of this study is to investigate the efficacy and safety of ERAS in craniotomy. Studies of ERAS in craniotomy were systematically searched in PubMed, Embase, Cochrane, and Web of Science. Primary outcomes (total hospital stay and postoperative hospital stay, hospitalization cost, percent of patients with moderate to severe pain) and secondary outcomes (readmission rate and incidence of complication) were compared between ERAS and traditional perioperative care. Of the 10 studies included in this meta-analysis, 6 were randomized-controlled trials (RCTs), 3 were cohort studies, and 1 was non-RCT. A total of 1275 patients were included, with 648 in the ERAS group and 627 in the control group. Compared with the control group, the ERAS group had a significantly shortened total length of stay (LOS) (MD = -2.437, 95% CI: -3.616, -1.077, P = 0.001) and postoperative LOS, reduced hospitalization cost (SMD = -0.631, 95% CI: -0.893, -0.369, P = 0.001), and lower percent of patients with moderate to severe pain. There was no significant difference in readmission rate between the two groups. Though, the ERAS group had a significantly lower risk of pneumonia than the control group. ERAS is safe and effective for craniotomy as it shortens total and postoperative LOS, reduces hospitalization costs, decreases the percent of patients with moderate to severe pain.


Effect of individualized treatment strategy on postoperative nausea and vomiting in gynaecological laparoscopic surgery: a double-blind, randomized, controlled trial.
Postoperative nausea and vomiting (PONV) have always been a concern of clinicians and may increase medical costs for patients. Consensus guidelines recommend using multiple antiemetics with different mechanisms as prophylaxis in patients at high risk of PONV. Individualized risk scores for nausea and vomiting and individualized treatment strategies are feasible. This study evaluated the effect of individualized treatment strategies on postoperative nausea and vomiting after laparoscopic gynaecological operations. This was a double-blind, randomized, controlled trial. A total of 119 adult patients who underwent gynaecological laparoscopic surgery under general anaesthesia were randomly divided into an individualized treatment group or a control group, with the individualized treatment group receiving individualized prevention according to a preoperative risk score of nausea and vomiting and the control group receiving no individualized prevention. Vomiting, retching, nausea, and use of rescue medication were all recorded for 24 h after the operation. The primary outcome variable was complete response, defined as no emesis or the use of rescue medication 24 h postoperatively. The complete response rate was higher in the individualized treatment group (56.7%) than in the control group (23.7%) (95% CI, 0.01-0.27; P < 0.001). The incidences of emesis (18.3% vs. 44.1%, P = 0.002) were significantly lower in the individualized treatment group than in the control group. There were no differences in any nausea (26.7% vs. 33.9%, P = 0.391) or rescue medication use (6.7% vs. 8.5%, P = 0.743). Adverse events and laboratory and electrocardiogram abnormalities occurred no more frequently in the individualized treatment group than in the control group. In conclusion, this single-centre, double-blind, randomized study suggests that an individualized PONV prophylactic treatment strategy based on the number of PONV risk factors could be a safe and effective regimen to reduce the incidence of PONV in adult patients undergoing laparoscopic gynaecological surgery.


Present state and perspective of downstream processing of biologically produced 1,3-propanediol and 2,3-butanediol.
1,3-Propanediol and 2,3-butanediol are two promising chemicals which have a wide range of applications and can be biologically produced. The separation of these diols from fermentation broth makes more than 50% of the total costs in their microbial production. This review summarizes the present state of methods studied for the recovery and purification of biologically produced diols, with particular emphasis on 1,3-propoanediol. Previous studies on the separation of 1,3-propanediol primarily include evaporation, distillation, membrane filtration, pervaporation, ion exchange chromatography, liquid-liquid extraction, and reactive extraction. Main methods for the recovery of 2,3-butanediol include steam stripping, pervaporation, and solvent extraction. No single method has proved to be simple and efficient, and improvements are especially needed with regard to yield, purity, and energy consumption. Perspectives for an improved downstream processing of biologically produced diols, especially 1,3-propanediol are discussed based on our own experience and recent work. It is argued that separation technologies such as aqueous two-phase extraction with short chain alcohols, pervaporation, reverse osmosis, and in situ extractive or pervaporative fermentations deserve more attention in the future.


Problematic Internet Use in adolescents: New psychometric evidence for the Spanish short form of the Compulsive Internet Use Scale.
Problematic Internet Use (PIU) has become a worldwide problem in recent years. Among screening instruments for PIU, the Compulsive Internet Use Scale (CIUS) is perhaps the most widely used. Psychometric properties of the full CIUS are not convincing, however, and the short form (CIUS-S) has shown promising results, albeit limited to the English version, with little evidence in Spanish. Therefore, the aim of the present work was to study the psychometric properties of the CIUS-S scores in a large sample of Spanish adolescents. The sample consisted of 1790 participants, 816 male (45.6%), 961 female (53.7%), and 13 other (0.7%) . Mean age was 15.70 years (SD = 1.26). The five-items one-dimensional model displayed appropriate goodness-of-fit indices. Strong measurement invariance model across age and partial across gender was found. Furthermore, the CIUS-S was positively associated with several indicators of poor well-being and mental health, and negatively associated with prosocial behavior, self-esteem, and feeling of belonging. Overall, the CIUS-S scores appear reliable and valid in its Spanish version for adolescent populations, supporting its aim to detect and prevent a problem that has become a major worldwide issue in the last years.


The interaction of Cibacron Blue F3GA with troponin and its subunits.
Binding of troponin to Cibacron Blue F3GA-agarose column and its selective release from the gel in the presence of 0.5 M KCl provides the basis for a new purification method. The two-step procedure consists of isoelectric precipitation of tropomyosin and chromatography of the resultant crude troponin supernatant on Affi-Gel Blue column. Adsorption of troponin to the immobilized dye appears to occur through the troponin-T subunit. Troponin-I and troponin-C do not bind to the blue agarose column, whereas troponin-T binds to it very tightly. Binding of the dye to troponin-T prevents formation of troponin-T-troponin-C complex, but does not interfere with direct interaction of troponin-T with troponin-I. The activity of troponin in conferring calcium sensitivity on actomyosin ATPase is not affected by Cibacron Blue. Circular dichroism and difference absorption measurements of complexes of the blue dye with troponin and its subunits reveal the presence of a tight binding site on whole troponin and on troponin-T (KA greater than or equal to 10(6) M). The existence of weak binding sites for the dye on troponin and all of its subunits is deduced from difference absorption studies. Cibacron Blue appears to be a sensitive probe for subunit interactions in troponin.


Fluconazole in the management of endophthalmitis in disseminated candidosis of heroin addicts.
Seven heroin addicts were treated with fluconazole for endophthalmitis. All the patients had cutaneous lesions: deep-seated scalp nodules and/or pustulosis in hairy zones. One patient had an abscess at the venipuncture site. Candida albicans was isolated from all the extraocular sites in all the patients. Five patients were treated with 400 mg of intravenous fluconazole on the first day, followed by 200 mg (i.v.) for one week and finally 200 mg daily orally for a further two weeks. Two patients were treated exclusively with oral fluconazole (400 mg on the first day, followed by 200 mg daily for three consecutive weeks). Tolerance to fluconazole was good and it was not necessary to stop treatment for any patient. All the cutaneous lesions stabilized and healed. The eye lesions cleared completely in all cases, except in one patient in whom vitrectomy was indicated, and in whom there was a poor response to the exclusive treatment with fluconazole and associated corticosteroids.


Phonon Polaritonics in Broad Terahertz Frequency Range with Quantum Paraelectric SrTiO3.
Photonics in the frequency range of 5-15 terahertz (THz) potentially open a new realm of quantum materials manipulation and biosensing. This range, sometimes called "the new terahertz gap", is traditionally difficult to access due to prevalent phonon absorption bands in solids. Low-loss phonon-polariton materials may realize sub-wavelength, on-chip photonic devices, but typically operate in mid-infrared frequencies with narrow bandwidths and are difficult to manufacture on a large scale. Here, for the first time, quantum paraelectric SrTiO3 enables broadband surface phonon-polaritonic devices in 7-13 THz. As a proof of concept, polarization-independent field concentrators are designed and fabricated to locally enhance intense, multicycle THz pulses by a factor of 6 and increase the spectral intensity by over 90 times. The time-resolved electric field inside the concentrators is experimentally measured by THz-field-induced second harmonic generation. Illuminated by a table-top light source, the average field reaches 0.5 GV m-1 over a large volume resolvable by far-field optics. These results potentially enable scalable THz photonics with high breakdown fields made of various commercially available phonon-polariton crystals for studying driven phases in quantum materials and nonlinear molecular spectroscopy.


Authoritarian and benevolent god representations and the two sides of prosociality.
The Big Gods model focuses on belief in an authoritarian God as a psychological mechanism that inhibits antisocial behavior and facilitates the formation of tight, cohesive groups. Recent empirical evidence suggests, however, that belief in a benevolent God is more likely to inspire helping and inclusivity. Both kinds of beliefs are necessary to explain the development of large-scale societies.


Surgical treatment of salivary gland tumors.
Two hundred fifteen patients (74.14%) with benign tumors and 75 patients (25.86%) with malignant tumors of the salivary glands were analyzed. One hundred eighty-five of these patients were followed for 1 to 20 years postoperatively. Of 150 benign tumors, recurrence was noted in 15 cases (9.75%). The 5-year recurrence rate was 7.82%. With the malignant tumors, recurrence was noted in 16 patients (51.6%). The 5-year recurrence rate was 27.75%.


Comparison of ultrasound-assisted emulsification and dispersive liquid-liquid microextraction methods for the speciation of inorganic selenium in environmental water samples using low density extraction solvents.
Herein, ultrasound-assisted emulsification microextraction (USAEME) and dispersive liquid-liquid microextraction (DLLME) methods based on applying low-density organic solvents have been critically compared for the speciation of inorganic selenium, Se(IV) (selenite) and Se(VI) (selenate) in environmental water samples by gas chromatography-flame ionization detection (GC-FID). At pH 2 and T=75°C for 7 min, only Se(IV) was able to form the piazselenol complex with 4-nitro-o-phenylenediamine. Piazselenol was extracted using an extraction solvent and was injected into a GC-FID instrument for the determination of Se(IV). Conveniently, Se(VI) remained in the aqueous phase. Total inorganic selenium was determined after the reduction of Se(VI) to Se(IV) and prior to the above procedures. The Se(VI) concentration was calculated as the difference between the measured total inorganic selenium and Se(IV) content. The effect of various experimental parameters on the efficiencies of the two methods and their optimum values were studied with the aid of response surface methodology and experimental design. Under the optimal conditions, the limit of detections (LODs) for Se(IV) obtained by USAEME-GC-FID and DLLME-GC-FID were 0.05 and 0.11 ng mL(-1), respectively. The relative standard deviations (RSDs, n=6) for the measurement 10 ng mL(-1) of Se(IV) were 5.32% and 4.57% with the enrichment factors of 2491 and 1129 for USAEME-GC-FID and DLLME-GC-FID, respectively. Both methods were successfully applied to the analysis of inorganic selenium in different environmental water samples and certified reference material (NIST SRM 1643e).


[Histological examination of changes due to aging in the femur compacta of laboratory and house mice].
The age changes in the histological structure of the femur corticalis in ICR laboratory mice (from 20 to 300 days) and in house mice (from 50 to 520 days) were studied. In both forms of mice the circumferential lamellae prevailed, with increased age they are substitued by secondary but mainly primary Haversian systems and the interstitial systems of vartious shape. Certain differences in the construction of the femur corticalis, were found in both species of mice; from among the latter the mouse is more suitable for the demonstration of age changes.


Avalanche Safety Practices Among Backcountry Skiers and Snowboarders in Jackson Hole in 2016.
Carrying standard safety gear (beacon, probe, and shovel), planning a route of descent, and recreating with companions can help to mitigate the risk of injury or death resulting from avalanches in the backcountry. The goal of this study was to identify factors associated with performance of these safety practices. A convenience sample of backcountry skiers and snowboarders was surveyed in 2016 at the backcountry gates of Jackson Hole Mountain Resort. Each participant was surveyed on characteristics including skill level, sex, age, prior avalanche education, and residency in the Jackson Hole area. Safety practices were also measured against avalanche hazard forecasts. Correlations were assessed using Fisher's exact testing. A total of 334 participants were surveyed. Factors associated with carrying avalanche safety gear included higher expertise, being a resident of the Jackson Hole area, and prior avalanche education. Factors associated with having a planned route of descent included higher expertise and being a resident of the Jackson Hole area. Factors associated with recreating with companions included younger age and lower expertise. Sex had no association with any of the surveyed safety practices. Participants were less likely to carry avalanche safety gear on low avalanche hazard days. Certain individual characteristics of backcountry skiers and snowboarders are associated with increased frequency of adherence to recommended safety practices. These findings suggest that particular categories of backcountry recreationists may benefit from further avalanche safety education. The results of this study could help direct future educational efforts among backcountry recreationists.


Inhibition of nitrogen mustard induced DNA repair synthesis by anthracyclines in human peripheral leukocytes.
DNA repair synthesis was induced by nitrogen mustard in human peripheral leukocytes. When the cells were treated with increasing doses of doxorubicin or daunorubicin a decrease of the DNA repair synthesis was recorded. Daunorubicin had a significantly higher inhibitory effect on the DNA repair synthesis compared to doxorubicin. The inhibitory effect by doxorubicin or daunorubicin on nitrogen mustard induced DNA repair synthesis was compared with the inhibitory effect on replicative DNA and RNA synthesis in human lymphoblasts. The inhibition of DNA repair synthesis was significantly lower than the inhibition of replicative DNA synthesis and RNA synthesis for both drugs.


Usefulness of early rule-in and rule-out biomarker protocols to estimate ischemia-induced myocardial injury in early chest pain presenters.
Protocols to minimize the time between 2 measurements of troponin or a combination with copeptin have been developed to rapidly rule-in or rule-out myocardial injury (MI) in patients with chest pain. These fast track protocols to rule-in and rule-out MI are not sufficiently validated for early chest pain presenters. The "early presenter" model was tested in 107 stable patients after a short period of myocardial ischemia, induced by stenting of a significant coronary artery stenosis. High-sensitivity troponin T (hsTnT), high-sensitivity troponin I (hsTnI), and copeptin were measured at the start and 90, 180, and 360 minutes after stent implantation. MI was defined as a troponin level more than the upper limit of normal (ULN) and an absolute increase of >50% ULN on the 360-minute sample. A single combined measurement of troponin and copeptin 90 minutes after the onset of ischemia has a low diagnostic value. This increases when serial measurements with 90-minute intervals are included. For ruling in MI, the highest positive predictive value (with a 95% confidence interval [CI]) can be obtained when focusing only on the increase in troponin level, with a positive predictive value of 86% (70, 93) and 80% (67, 90) for hsTnT and hsTnI, respectively. For ruling out MI, a combined absence of any troponin more than the ULN and any significant increase in troponin level perform best with a negative predictive value of 75% (55, 89) and 75% (55, 89) for hsTnT and hsTnI, respectively. In conclusion, in early presenters, rapid biomarker protocols underestimate MI. A standard biomarker assessment after 3 hours is required to adequately rule-in or rule-out myonecrosis.


Clathrin-Mediated Auxin Efflux and Maxima Regulate Hypocotyl Hook Formation and Light-Stimulated Hook Opening in Arabidopsis.
The establishment of auxin maxima by PIN-FORMED 3 (PIN3)- and AUXIN RESISTANT 1/LIKE AUX1 (LAX) 3 (AUX1/LAX3)-mediated auxin transport is essential for hook formation in Arabidopsis hypocotyls. Until now, however, the underlying regulatory mechanism has remained poorly understood. Here, we show that loss of function of clathrin light chain CLC2 and CLC3 genes enhanced auxin maxima and thereby hook curvature, alleviated the inhibitory effect of auxin overproduction on auxin maxima and hook curvature, and delayed blue light-stimulated auxin maxima reduction and hook opening. Moreover, pharmacological experiments revealed that auxin maxima formation and hook curvature in clc2 clc3 were sensitive to auxin efflux inhibitors 1-naphthylphthalamic acid and 2,3,5-triiodobenzoic acid but not to the auxin influx inhibitor 1-naphthoxyacetic acid. Live-cell imaging analysis further uncovered that loss of CLC2 and CLC3 function impaired PIN3 endocytosis and promoted its lateralization in the cortical cells but did not affect AUX1 localization. Taken together, these results suggest that clathrin regulates auxin maxima and thereby hook formation through modulating PIN3 localization and auxin efflux, providing a novel mechanism that integrates developmental signals and environmental cues to regulate plant skotomorphogenesis and photomorphogenesis.


Differentiation of the sibling species Biomphalaria occidentalis and Biomphalaria tenagophila by the electrophoretic patterns of their hemoglobin.
A simple and rapid method for differentiating the sibling species Biomphalaria tenagophila and Biomphalaria occidentalis by agarose gel electrophoresis (AGE) is described. Snail hemolymph is used as the test sample and the red coloration of the hemoglobin fraction permits visualization of the migration patterns without resorting to specific stains. Moreover, hemolymph samples may be obtained without killing the snail, thus permitting its use for other studies or for breeding.


Determination of theophylline and its metabolites in plasma and urine by reversed-phase liquid chromatography using an amine modifier.
A high-performance liquid chromatographic method for the determination of the concentrations of theophylline and its metabolites in plasma and urine samples is presented. The method uses the decylammonium ion, an N-alkylammonium modifier, and makes it possible to separate theophylline and its metabolites from other uric acid or xanthine derivatives, especially 1,7-dimethylxanthine, a metabolite of caffeine. The plasma and urine purification procedure is convenient, rapid and reproducible, and it can be used to determine low plasma and urine concentrations.


Estimation of canine prostatic size by in vivo ultrasound and volumetric measurement.
Two methods for estimating the weight of the canine prostate gland in vivo were investigated. Twenty-six beagle dogs underwent transrectal and transabdominal ultrasound examination of the prostate, followed by careful, standardized caliper measurement of the prostate at surgical exploration. The prostate glands were then removed and weighed, and nomograms were constructed for use in future laboratory research. The validity of these nomograms for determining prostate weight in vivo was confirmed on evaluation of 6 additional dogs.


Rapid regulation of neuronal growth cone shape and surface morphology by nerve growth factor.
Scanning electron microscopy was used to study regulation of growth cone shape and surface morphology by nerve growth factor (NGF). The growth cones of cultured rat sympathetic neurons and neuronally-differentiated PC12 cells were observed under conditions of continuous NGF exposure, NGF withdrawal, and NGF readdition. Growth cones of cells cultured in the continuous presence of NGF were mostly spread in shape and about 60% possessed surface ruffles. Ruffles appeared to be largely restricted to growth cones in that few were observed on cell bodies and neurites. Withdrawal of NGF for 4-5 hr caused most of the growth cones to take on a non-spread or contracted appearance and to lose their ruffles. Readdition of NGF promoted rapid changes in growth cone properties. Within 30 sec, ruffling was again evident on the growth cones and remained prominent there throughout the course of treatment (up to 5 hr). This was in contrast to cell bodies on which, as previously reported, ruffling also occurred following NGF readdition, but only transiently (for less than 15 min). Respreading of growth cones also occurred under these conditions. This was evident within 1 min of NGF readdition and reached the levels observed in continuously-treated cultures within 1-2 hr. Neurites were also examined. Ruffles were only rarely present in the continuous presence of NGF and were absent after NGF withdrawal. NGF readdition elicited ruffling along neurites within 30 sec; the prevalence of such ruffles diminished to that seen in continuously-treated cultures within about an hour.(ABSTRACT TRUNCATED AT 250 WORDS)


Intracranial capillary hemangioma: case report and review of the literature.
Capillary hemangiomas are benign vascular lesions that commonly present at birth or in early infancy on the face, scalp, back, or chest. The authors present an exceedingly rare case of an intracranial capillary hemangioma arising in an adult. Only 4 biopsy-proven cases have been reported in the pediatric population previous to this case report. A 31-year-old pregnant woman presented at 38 weeks of gestation with severe headaches, nausea, and vomiting. Imaging revealed an extra-axial mass lesion arising from the tentorium with both supra- and infratentorial components. The patient underwent a resection of her tumor, which was diagnosed as a capillary hemangioma by histopathologic examination. The patient required 2 further resections after the lesion exhibited a rapid regrowth from residual tumor in the left transverse sinus. The patient has remained free of disease 41 months out from her third surgery. Intracranial capillary hemangiomas are exceedingly rare entities, with a capability for rapid growth. When gross total resection cannot be achieved, these patients should be observed closely, and the use of adjuvant radiotherapy should be considered.


On the interaction between fluoxetine and lipid membranes: Effect of the lipid composition.
Molecular interaction between the antidepressant fluoxetine and lipid bilayers was investigated in order to provide insights into the drug's incorporation to lipid membranes. In particular, the effects of lipid's unsaturation degree and cholesterol content on the partitioning of fluoxetine into large unilamellar vesicles (LUVs) comprised of unsaturated 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and saturated 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) were evaluated using second derivative spectrophotometry and Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR). It was found that fluoxetine partitioned to a greater extent into the liquid-crystalline DOPC LUVs than into the solid-gel DPPC LUVs. The lipid physical state dependence of drug partitioning was verified by increasing the temperature in which the partition coefficient of fluoxetine significantly increased upon the change of the lipid phase from solid-gel to liquid-crystalline. The incorporation of 28mol% cholesterol into the LUVs exerted a significant influence on the drug partitioning into both DOPC and DPPC LUVs. The ATR-FTIR study revealed that fluoxetine perturbed the conformation of DOPC more strongly than that of DPPC due to the cis-double bonds in the lipid acyl chains. Fluoxetine possibly bound to the carbonyl moiety of the lipids through the hydrogen bonding formation while displaced some water molecules surrounding the PO2- regions of the lipid head groups. Cholesterol, however, could lessen the interaction between fluoxetine and the carbonyl groups of both DOPC and DPPC LUVs. These findings provided a better understanding of the role of lipid structure and cholesterol on the interaction between fluoxetine and lipid membranes, shedding more light into the drug's therapeutic action.


One-year renal outcome in lupus nephritis patients with acute kidney injury: a nomogram model.
To develop a short-term renal outcome prediction model for acute kidney injury (AKI) in patients with LN. Two lupus AKI cohorts from two independent centres during 2013-2019 were included: a derivation cohort from a rheumatology centre and a validation cohort from a nephrology centre. Clinical characteristics and renal histologic features were obtained. The outcome measurement was the recovery of kidney function within 12 months. Lasso regression was used for feature selection. Prediction models with or without pathology were built and a nomogram was plotted. Model evaluation including calibration curve and decision curve analysis was performed. A total of 130 patients were included in the derivation cohort and 96 patients in the validation cohort, of which 82 and 73 patients received a renal biopsy, respectively. The prognostic nomogram model without pathology included determinants of SLE duration, days from AKI onset to treatment and baseline creatinine level [C-index 0.85 (95% CI 0.78, 0.91) and 0.79 (95% CI 0.70, 0.88) for the two cohorts]. A combination of histologic tubulointerstitial (TI) fibrosis in the nomogram gave an incremental predictive performance (C-index 0.93 vs 0.85; P = 0.039) in the derivation cohort but failed to improve the performance in the validation cohort (C-index 0.81 vs 0.79; P = 0.78). Decision curve analysis suggested clinical benefit of the prediction models. The predictive nomogram models might facilitate more accurate management for lupus patients with AKI.


Fractionated high-dose rate brachytherapy for intracranial gliomas.
To develop a catheter system for fractionated high-dose rate (HDR) brachytherapy for intracranial gliomas. The catheter system for stereotactic placement as well as delivery of the high-dose rate iridium-192 source wire is described. The force of the impulse wave from the source wire entering brain equivalent material was measured. Dose volume histograms for the first 5 patients treated are presented. The catheter system was found to be satisfactory. The maximum force of the impulse wave was less than 1 acceleration of gravity (which is safe). The patients tolerated the treatment well with no significant problems related to the catheters being left in situ for up to 14 days. Based on this pilot experience a phase I dose escalating and morbidity study has been initiated.


19F MRS studies of fluoropyrimidine chemotherapy. A review.
19F NMR spectroscopy (MRS) has been used to follow the metabolism of the fluoropyrimidine anticancer drug 5-fluorouracil and its derivatives non-invasively, both in animals and humans. This review is concerned with the information that has been acquired concerning cytotoxicity and detoxification in relation to studies performed with conventional methods. The potential uses of 19F MRS of fluoropyrimidines in research, particularly concerning combination chemotherapy, and in monitoring therapy, are discussed.


Magnesium infusion improves endothelium-dependent vasodilation in the human forearm.
The effect of intra-arterial magnesium infusion on endothelium-dependent vasodilation (EDV) in the forearm was studied in nine young healthy students (four men and five women). The EDV was assessed as forearm blood flow (FBF), measured by venous occlusion plethysmography, during infusion of methacholine (MCh). Endothelium-independent vasodilation (EIDV) was defined as FBF during infusion of sodium nitroprusside (SNP). During magnesium infusion in the brachial artery, 0.066 mmol/min, the concentration of ionized magnesium in venous plasma in the infused arm increased by 114%, from 0.59 (SD 0.04) to 1.26 (0.34) mmol/L (P = .0002). The FBF at baseline (ie, before administration of MCh or SNP) increased from 3.5 (1.1) to 7.3 (3.4) mL/min/100 mL tissue during magnesium infusion (P = .002). During low-dose MCh administration (2 microg/min), FBF increased by 24%, from 15.4 (5.5) to 19.1 (6.8) mL/min/100 mL tissue (P = .04), and during high-dose MCh administration (4 microg/min) FBF increased by 18%, from 20.3 (6.4) to 24.0 (7.2) mL/min/100 mL tissue (P = .04). The EIDV did not change significantly. Systemic blood pressure was not significantly altered by magnesium infusion. No change in FBF either at rest or during infusion of MCh or SNP was observed during the time-control protocol. In conclusion, this in vivo study showed that intraarterial magnesium infusion increased EDV in the infused human forearm, which is in accordance with findings in previous in vitro and animal experiments.


The two faces of DJ-1D proteins.
Despite the documented bi-enzymatic mode of methylglyoxal detoxification, the single-step catalysis of methylglyoxal by DJ-1/Pfp-I domain containing proteins has been in the limelight. Prasad et al. recently discovered another functional facet of these moonlighting proteins: the deglycase potential of DJ-1D to repair the glycated DNA, RNA, and proteins in plants.


The chemical structure and the crystalline structures of Bombyx mori silk fibroin.
Some recent data (i.e. published in the last ten years) on the chemical and crystalline structures of B. mori silk are reviewed. The main emphasis is put on the crystallizable portion of silk fibroin, including its chemical constitution and its molecular conformation (at the crystallographic unit-cell level) in the two crystalline modifications : the beta pleated sheet and the silk I structures. The structural aspects are based on a discussion of X-ray and electron diffraction data, and on conformational energy analyses of a model (Ala-Gly)n polypeptide of silk fibroin.


Replication control and cellular life span.
Cell proliferation involves both control of progress through the current cell cycle and coordination of successive cell cycles. We have focused our attention on the events that trigger traversal of the G1/S boundary of the cell cycle. A protein kinase activity was found in preparations of the DNA-replicative complex from the budding yeast Saccharomyces cerevisiae. The activity phosphorylated only a few of the proteins present in the replicative fraction, and it displayed a marked preference for a 48-kDa polypeptide. Most importantly, the protein kinase activity was heat-sensitive in replicative fractions from cdc7 cells, a mutant that arrests at the G1/S boundary at restrictive temperature. The results suggest that phosphorylation of components of the replication machinery may play a role in control of initiation of DNA replication during the cell cycle. We have also begun an analysis of cellular aging in yeast, as a means of addressing the problem of coordination of successive cell cycles. Yeast cells have a finite life span defined by reproductive capacity. With age, the generation time of yeast cells lengthened. The cell cycle of the daughter cell was under the control of the mother. This control was transient, and the daughter cell began dividing at the rate characteristic of its own age within three divisions of its birth. This suggests that the senescent phenotype, as manifested by lengthened generation time, is a dominant feature in yeast cells, and that it is determined by a diffusible cytoplasmic molecule(s) that undergoes turnover in young cells. In a search for this putative senescence factor(s), we are cloning genes that differentially expressed during the yeast life span. Several such genes have been isolated and partially characterized. Our goals are to determine whether the expression of one or more of these genes is casually associated with cell longevity. We propose the Cell Spiral model to describe the relationship between the cell cycle and cellular aging.


Transposition of Superior Cerebellar Artery for Microvascular Decompression in Trigeminal Neuralgia Using an In Situ Superior Petrosal Vein Sling Technique.
Several microvascular decompression technical variations for the treatment of medically refractory trigeminal neuralgia have been proposed that can be categorized generally as interposition and transposition techniques. These latter approaches, so-called slinging techniques, have been increasing in popularity, because they can possibly reduce the long-term recurrence rates by preventing the formation of fibrosis and granulomas at the decompression site. We have reported a technique for transposition of the superior cerebellar artery for microvascular decompression in trigeminal neuralgia using the superior petrosal vein as an in situ sling to anchor and reroute the artery away from the nerve. We have presented a technical report with illustrative intraoperative images and video from 2 cases of trigeminal neuralgia in which the superior petrosal vein was used as a simple and straightforward in situ sling for transposition of the superior cerebellar artery. The technique was applied successfully in 2 patients with complete and immediate remission of trigeminal neuralgia, without surgical morbidity. The most frequent neurovascular conflict in trigeminal neuralgia involves the superior cerebellar artery, and the strategic location of the superior petrosal vein relative to this neurovascular complex allows for its use as a natural in situ sling that reroutes the artery and prevents its recoil against the nerve. This technique can be added to the increasing armamentarium of transposition techniques for microvascular decompression, with the advantage of simplicity and no requirement for a complex prosthesis to secure the transposition.


Treatment for Appendicitis With Appendicolith by the Stone Size and Serum C-Reactive Protein Level.
Appendicolith causes acute appendicitis. However, surgical indications for appendicolith-related acute appendicitis have not been established. We aimed to clarify the clinical features of appendicolith-associated appendicitis and determine an appropriate treatment strategy based on the initial presentation. We retrospectively reviewed the records of 479 consecutive patients with acute appendicitis and verified the therapeutic strategy as per the appendicolith and clinical status. Appendicoliths were identified in 214 of 479 patients (44.6%) using computed tomography. Surgery was more frequently required in patients with appendicolith than in patients without appendicolith (82.7 versus 64.9%; P < 0.001). The stones were smaller and serum C-reactive protein (CRP) concentration was lower among patients with appendicoliths treated with medication alone than among those surgically treated (both P < 0.001). An appendicolith measuring ≤5 mm in diameter and CRP concentration ≤5.36 mg/dL were predictive of completion of nonsurgical therapy. CRP concentration >10 mg/dL and stone diameter of 10 mm were significantly associated with appendiceal perforation. Nonsurgical therapy could be considered for patients with appendicoliths measuring ≤5 mm in diameter and in cases where the serum CRP concentration is ≤5 mg/dL. An appendicolith measuring >10 mm in diameter or CRP concentration >10 mg/dL is an indication for surgery.


Challenging direct bypass surgery for very young children with moyamoya disease: technical notes.
Cerebral revascularization for moyamoya disease (MMD) is an effective treatment for improving cerebral ischaemia and preventing rebleeding. Although direct bypass surgery is commonly performed on older children and adults, it is challenging in very young children due to the high difficulty level of the procedure. The subjects were MMD patients under 3 years of age on whom surgery was performed by a single surgeon (Y.A.). Preoperative clinical findings, information related to direct bypass surgery, bypass patency, and the incidence of postoperative stroke were investigated. Combined revascularization, including direct bypass surgery, was performed on 3 MMD patients (3 sides) under 3 years of age. The average diameter of the grafts used in direct bypass was 0.8 mm. The average recipient diameter was 0.8 ± 0.17 (range 0.6-1) mm. In all cases, the anastomotic procedure was completed using 11-0 monofilament nylon thread, and patency was confirmed. Direct bypass for MMD patients under 3 years old is technically challenging. However, despite the anatomical differences between very young children and elderly individuals, direct bypass surgery could certainly be completed. In addition, a rapid recovery from cerebral blood flow insufficiency could yield a promising neurological outcome.


Evaluation of T-cell subsets in pregnant women infected with SARS-CoV-2.
Immune responses to SARS-CoV-2 are the main cause of tissue damage in coronavirus disease 2019. However, the pathophysiological mechanism of the disease has not been fully elucidated. The aim of this study was to examine T cell subsets of pregnant women infected with SARS-CoV-2 and evaluate the relationship between the possible differences in trimesters and clinical findings of the disease. Fifty-six pregnant patients with SARS-CoV-2 and 61 healthy pregnant controls were included in the study. T cell subsets were analyzed by flow cytometry. The CD3+ total T cell (p = 0.006 and p = 0.027) of pregnant patients infected with SARS-CoV-2 in second and third trimesters was found to be lower than in the control group. CD3+CD4+ helper T cell (p = 0.035), Treg (p = 0.001), and Treg/Th17 ratio (p = 0.001) were found to be lower in the third trimester patients infected with SARS-CoV-2 than in the controls. Significant decreases were observed only in the Treg (p = 0.001) and Treg/Th17 ratio (p = 0.001) in the first trimester patients infected with SARS-CoV-2 compared to the controls. When trimesters were compared in terms of T subsets, no difference was found (p > 0.05). The CD3+ total T cell (p = 0.001), CD3+CD4+ helper T cell (p = 0.011), Treg (p = 0.001), and Treg/Th17 ratio (p = 0.001) were found to be lower in pregnant women infected with SARS-CoV-2. This difference was associated with the development of pneumonia but not with adverse pregnancy outcomes.


An Investigation of Micro-CT Analysis of Bone as a New Diagnostic Method for Paleopathological Cases of Osteomalacia.
This paper looks to broaden the methodological possibilities for diagnosing osteomalacia in archaeological bone using micro-CT analysis. Increasing the identification of osteomalacia in paleopathology will provide support for important interpretive frameworks. Nine embedded and two unembedded rib fragments were sourced from St. Martin's Birmingham and Ancaster, UK, and Lisieux Michelet, France. Of the 11 samples, nine were previously confirmed as osteomalacic, and presented with varying levels of diagenesis and two were non-osteomalacic controls, one of which exhibits diagenetic change. Micro-CT, backscattered scanning electron microscopy, and light microscopy were employed. Micro-CT images were evaluated for osteomalacic features using corresponding microscopic images. Micro-CT images from osteomalacic samples demonstrated the presence of defective mineralization adjacent to cement lines, areas of incomplete mineralization, and resorptive bays/borders, three key diagnostic features of osteomalacia. Diagenetic change was also detectable in micro-CT images, but did not prevent the diagnosis of osteomalacia. Micro-CT analysis is a non-destructive method capable of providing microstructural images of osteomalacic features in embedded and unembedded samples. When enough of these features are present, micro-CT images are capable of confirming a diagnosis of osteomalacia. Vitamin D deficiency has important health consequences which operate throughout the life course. Increasing the ability to detect cases of vitamin D deficiency provides researchers with a greater understanding of health and disease in past communities. Only adult rib samples were used. Paleopathologists should look to test the utility of micro-CT analysis in diagnosing active rickets in subadult individuals.


Anorectic activity of prostaglandin precursors.
1 Intraperitoneal and intragastric (i.g.) administration of prostaglandin precursors arachidonic (2 mg, 15 mg/kg, i.p; 30 mg/kg i.g.), linolenic (100 mg/kg i.p.; 200 mg/kg, i.g.) and linoleic (15, 100 mg/kg, i.p.; 100 mg/kg, i.g.) acids to 22 h food-deprived rats inhibits food intake. 2 This anorexia is similar to that induced by prostaglandin F2alpha (1 mg/kg, i.p.). 3 At anorectic doses these fatty acids do not cause pyrexia, in fact arachidonic acid causes hypothermia. 4 Prior treatment with indomethacin (15 mg/kg) and paracetamol (50 mg/kg) specifically reverses the anorexia and the behavioural satiety induced by the three fatty acids, while not affecting prostaglandin F2alpha-induced suppression of food intake. 5 Results of the present experiments suggest that both physiological and pharmacological modification of appetite could be brought about through an effect on prostaglandin generating systems.


Advanced serrated polyps as a target of screening: detection rate and positive predictive value within a fecal immunochemical test-based colorectal cancer screening population.
BACKGROUND : Advanced serrated polyps (ASPs) have a comparable risk to advanced adenomas for progression to colorectal cancer (CRC). The yield of most CRC screening programs, however, is based on advanced adenomas and CRC only. We assessed the ASP detection rate, and positive predictive value (PPV) including ASPs in a fecal immunochemical test (FIT)-based screening program. METHODS : We analyzed the findings of follow-up colonoscopies of FIT-positive screenees in the Dutch CRC screening program from 2014 until 2020. Data were retrieved from the national screening and pathology database. An ASP was defined as any serrated polyp of ≥ 10 mm, sessile serrated lesion with dysplasia, or traditional serrated adenoma. The ASP detection rate was defined as the proportion of colonoscopies with ≥ 1 ASP. PPV was originally defined as the proportion of individuals with a CRC or advanced adenoma. The updated PPV definition included CRCs, advanced adenomas, and/or ASPs. RESULTS : 322 882 colonoscopies were included in the analyses. The overall detection rate of ASPs was 5.9 %. ASPs were detected more often in women than men (6.3 % vs. 5.6 %; P < 0.001). ASP detection rates in individuals aged 55-59, 60-64, 65-69, and 70 + were 5.2 %, 6.1 %, 6.1 %, and 5.9 %, respectively (P < 0.001). The PPV for CRCs and advanced adenomas was 41.1 % and increased to 43.8 % when including ASPs. The PPV increase was larger in women than in men (3.2 vs. 2.4 percentage points). CONCLUSIONS : 5.9 % of FIT-positive screenees had ASPs, but half of these were detected in combination with a CRC or advanced adenoma. Therefore, including ASPs results in a small increase in the yield of FIT-based screening.


Regulatory mechanisms of SNAT2, an amino acid transporter, in L6 rat skeletal muscle cells by insulin, osmotic shock and amino acid deprivation.
Several studies have demonstrated that the activity of system A is upregulated by insulin, osmotic shock and amino acid deprivation. However, the mechanisms are not clear. We carried out studies using L6 rat skeletal muscle cells to clarify the mechanisms of upregulation of system A activity by insulin, osmotic shock and amino acid deprivation. The upregulation was found to be due to an increase in Vmax, not Km. Chloroquine and wortmannin inhibited the upregulation induced by insulin stimulation and amino acid deprivation but not that induced by osmotic shock. On the other hand, cycloheximide and actinomycin D inhibited the upregulation by each stimulation. Moreover, PD98059 and SP600125 inhibited only amino acid deprivation-induced upregulation and SB202190 inhibited only insulin-induced upregulation. Our findings indicate that the mechanisms of upregulation of system A activity by insulin, osmotic shock and amino acid deprivation are different in L6 cells. Western blot and RT-PCR analysis showed an increase in system A at the protein and mRNA levels with each stimulation.


Primate cognition: putting two and two together.
The human mind has the capacity for abstract numerical representations that cut across different sensory modalities. New research with monkeys shows that this mathematical achievement is not unique to our species.


Mode of metabolism is altered in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-treated rats.
Male Sprague-Dawley rats were fed either a high-fat (HF) or a high-carbohydrate (HC) diet and subsequently injected with either 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (125 micrograms/kg) or vehicle (pair-fed controls). In all TCDD-treated animals, a reduction in caloric intake was evident as early as 1 day after dosage. Respiratory quotients (RQ) were determined at 5-day intervals. Their pattern for the HC-fed but not for the HF-fed TCDD-treated rats was different from that of the corresponding pair-fed controls. After an initial parallel decrease the RQ values remained low for TCDD-treated rats whereas they increased again for pair-fed controls. Serum total thyroxine (T4) was significantly lower in TCDD-treated animals and this reduction was not influenced by the composition of the diet. Serum triiodothyronine (T3) was neither altered by diet nor by TCDD. Thymic atrophy was as severe in pair-fed as in TCDD-treated rats fed the HC diet but not in rats fed the HF diet. Our results suggest that TCDD-treated rats are in a different mode of metabolism from pair-fed rats and that this difference is related to gluconeogenesis.


Oral verruciform hyperkeratotic lesions indicating the presence of plantar or palmoplantar keratodermas.
Oral verruciform hyperkeratotic lesions (OVHLs) affecting the gingiva and palate are frequent in proliferative verrucous leukoplakia (PVL). Intraoral hyperkeratotic lesions can also be observed in epidermolytic keratodermas, albeit such association has received limited attention in oral and maxillofacial pathology. The authors report on 5 individuals whose plantar (PK) or palmoplantar keratodermas (PPKs) were confirmed after evaluation of gingival leukoplakic biopsies. Two women and 3 men, ages 18 to 64, presented with solitary or diffuse leukoplakias of the attached gingiva and hard palate, clinically interpreted as PVL. All individuals underwent diagnostic gingival and/or palatal biopsies. Microscopically, the lesions featured verruciform hyperparakeratosis, occasionally conspicuous hypergranulosis and acanthosis. In the spinous cell layer, numerous cells presented with vacuolated cytoplasm and paranuclear eosinophilic condensations that, infrequently, engulfed the nucleus. The histopathologic findings were interpreted as verrucous hyperkeratosis consistent with those described in epidermolytic PPKs. Further evaluation of the individuals for cutaneous lesions disclosed PK or PPKs in all 5 patients. Additionally, the men exhibited elbow and subungual hyperkeratoses. A family history of keratodermas was confirmed in all 3 male individuals. Gingival and/or palatal OVHLs associated with PK and PPKs display pathognomonic histopathologic features and exhibit indolent biologic behavior. Therefore, any confusion with PVL should be avoided to prevent overtreatment.


[Side effects of tumor pharmacotherapy. What internists should know].
Cytotoxic drugs have been used in the therapy of malignant tumors for the last 70 years. However, side effects of cytotoxic drugs are very common and often dose-limiting. Although many protocols have been optimized, side effects are still frequently life-threatening. Nausea and vomiting are among the most frequently reported side effects, in addition to mucositis and fatigue. Bone marrow toxicity can lead to neutropenic sepsis, thrombocytopenic bleeding, or anemia with the respective sequelae. In addition to these unspecific side effects, organ toxicity is class or drug specific and may involve the kidney, liver, heart, lung, skin, or central nervous system. As most protocols can be administered on an outpatient basis, knowledge of these side effects is important for the general internist.


Role of ventrolateral orbital cortex muscarinic and nicotinic receptors in modulation of capsaicin-induced orofacial pain-related behaviors in rats.
Acetylcholine, as a major neurotransmitter, mediates many brain functions such as pain. This study was aimed to investigate the effects of microinjection of muscarinic and nicotinic acetylcholine receptor antagonists and agonists into the ventrolateral orbital cortex (VLOC) on capsaicin-induced orofacial nociception and subsequent hyperalgesia. The right side of VLOC was surgically implanted with a guide cannula in anaesthetized rats. Orofacial pain-related behaviors were induced by subcutaneous injection of a capsaicin solution (1.5µg/20µl) into the left vibrissa pad. The time spent face rubbing with ipsilateral forepaw and general behavior were recorded for 10min, and then mechanical hyperalgesia was determined using von Frey filaments at 15, 30, 45 and 60min post-capsaicin injection. Alone intra-VLOC microinjection of atropine (a muscarinic acetylcholine receptor antagonist) and mecamylamine (a nicotinic acetylcholine receptor antagonist) at a similar dose of 200ng/site did not alter nocifensive behavior and hyperalgesia. Microinjection of oxotremorine (a muscarinic acetylcholine receptor agonist) at doses of 50 and 100ng/site and epibatidine (a nicotinic acetylcholine receptor agonist) at doses of 12.5, 25, 50 and 100ng/site into the VLOC suppressed pain-related behaviors. Prior microinjections of 200ng/site atropine and mecamylamine (200ng/site) prevented oxotremorine (100ng/site)-, and epibatidine (100ng/site)-induced antinociception, respectively. None of the above-mentioned chemicals changed general behavior. These results showed that the VLOC muscarinic and nicotinic acetylcholine receptors might be involved in modulation of orofacial nociception and hypersensitivity.


Acid aspiration prophylaxis in labour: a survey of UK obstetric units.
The risk of acid aspiration is still a major concern in pregnant patients. In view of the increasing numbers of drugs available to decrease gastric acid production, it seemed timely to reassess acid aspiration prophylaxis policies in the UK. An OAA-approved postal survey of 250 UK lead consultant obstetric anaesthetists was conducted in 2004 in order to establish the current practice of acid aspiration prophylaxis in labour. If acid aspiration prophylaxis was used, further questions were asked relating to subgroups of patients, category, dose and route of administration of drugs used and whether there was an anticipated change in practice. A response rate of 83% was achieved. There had been a decrease in the routine use of acid aspiration prophylaxis to 32% of units, an increase in the use of acid aspiration prophylaxis in "at risk" groups to 61% and a decrease in the number of units never using prophylaxis to 7%. Oral ranitidine administered six-hourly is the most common practice. There is little use of proton pump inhibitors. Compared to previous surveys of UK practice there has been an overall increase in the use of acid aspiration prophylaxis.


Histone demethylase KDM1A represses inflammatory gene expression in preadipocytes.
Persistent inflammation and impaired adipogenesis are frequent features of obesity and underlie the development of its complications. However, the factors behind adipose tissue dysfunction are not completely understood. Previously it was shown that histone demethylase KDM1A is required for adipogenesis. Kdm1a expression was knocked down in 3T3-L1 preadipocytes by siRNA transfection and whole-genome expression profiling was performed by microarray hybridization. The role of NF-κβ and C/EBPβ was analyzed by incubation with the inhibitor parthenolide and by cebpb knockdown, respectively. Knockdown of kdm1a or rcor2 in 3T3-L1 preadipocytes results in impaired differentiation and induction of inflammatory gene expression. Enhanced expression of il6 in kdm1a knocked down preadipocytes is associated with increased recruitment of C/EBPβ and the NF-κβ subunit RelA to the il6 promoter. Cebpb knockdown attenuates the induction of il6 expression in kdm1a knocked down cells, whereas simultaneous cebpb knockdown and NF-κβ inhibition abrogates it. Dietary-induced and genetic mouse models of obesity display decreased KDM1A in adipose tissue, and this correlates with increased expression of proinflammatory genes and C/EBPβ. KDM1A represses the expression of inflammatory genes in preadipocytes. Dysregulated kdm1a expression in preadipocytes may thus participate in the development of obesity-associated inflammation.


Functional outcome and depression in the elderly with or without fatigue.
We evaluated the influence of fatigue on functional outcomes and depression in older people. Fatigue was measured using the fatigue severity scale (FSS). Activity of daily living function was assessed using the functional independence measurement (FIM), the geriatric depression inventory (GDI) was used to assess depression. The average FSS score was 5.66 ± 1.03 for subjects in the fatigue group, with 50 patients (40.3%) having FSS scores ≥ 4 points. Significant relationships were found between fatigue and GDI (p<0.001, r = 0.363) and FIM (p<0.04, r = -0.183). Binary logistic regression analysis identified GDI as a significant predictor of fatigue (p < 0.001). We found that 40.3% of older people had fatigue. Fatigue showed a significant correlation with depression and functional status. These findings emphasize the need for careful clinical screening of both fatigue and depression in older individuals.


The epidemiology of non-typhoidal Salmonella gastroenteritis and Campylobacter gastroenteritis in pediatric inpatients in northern Taiwan.
Campylobacter and Non-typhoidal Salmonella (NTS) are the two most common bacterial pathogens associated with acute gastroenteritis in children. This study aims to elucidate the epidemiology of Campylobacter and NTS gastroenteritis and develop a scoring system to differentiate them. This retrospective study enrolled 886 children ≤18 years of age, hospitalized due to acute gastroenteritis with stool culture-proven Campylobacter or NTS infection from July 2012 to December 2015. Pearson's chi-square test and multivariate logistic regression were used to compare clinical manifestations and laboratory data. Receiver operating characteristic curves were plotted to evaluate the scoring system. Seasonality was found in NTS gastroenteritis from May to September, but no seasonality in Campylobacter gastroenteritis. Campylobacter jejuni and Salmonella serogroup B were the most common pathogens. The median ages were 68.2 and 18.5 months and the incidence rates of bacteremia were 0.6% and 7.1% in the Campylobacter and NTS groups, respectively. Salmonella serogroup C2 infection had the highest risk of bacteremia (OR: 5.9, 95% CI: 2.8-12.7, p < 0.001). Multivariate analysis showed significant differences in sex, age, fever, dehydration, immature WBC, CRP and Na between the two groups. A score of ≥2 points indicated Campylobacter gastroenteritis, with sensitivity 75%, specificity 77%. The positive and negative predictive values were of 73.3% and 93.9% after validation. Campylobacter gastroenteritis is associated with older age and male sex, while NTS gastroenteritis is associated with moderate to severe dehydration and bacteremia. Salmonella serogroup C2 infection has the highest risk of bacteremia.


Fullerene (C60)-based tumor-targeting nanoparticles with "off-on" state for enhanced treatment of cancer.
The traditional drug delivery systems always suffer from the unexpected drug release during circulation and the sluggish release of drug in target site. To address the problem, an "off-on" type drug delivery system with precise control was developed in this study. Doxorubicin (DOX) was covalently conjugated to fullerene (C60) nanoaggregates via a reactive oxygen species (ROS)-sensitive thioketal linker (C60-DOX NPs), and then the hydrophilic shell (Distearoyl-sn-glycero-3-phosphoethanolamine-PEG-CNGRCK2HK3HK11, DSPE-PEG-NGR) was attached to the outer surface of C60-DOX, giving it (C60-DOX-NGR NP) excellent stability in physiological solutions and active tumor-targeting capacity. C60-DOX-NGR NPs were able to entrap DOX efficiently even at acidic environment (pH5.5) when they were "off" state. In sharp contrast, when the NPs were "on" state, a large number of ROS were generated by C60, leading to the breaking of ROS-sensitive linker, thereby enabling the burst release of DOX. The "off" or "on" state of C60-DOX-NGR NPs could be precisely remote-controlled by a 532nm laser (at a low power density) with a high spatial/temporal resolution. In the in vivo and in vitro studies, the C60-based drug delivery system with "off-on" state exhibited a high antitumor efficacy and a low toxicity to normal tissues due to its tumor-targeting ability, remote-controlled drug release property and combined therapeutic effect (photodynamic therapy combined with chemotherapy).


Association between academic performance and cognitive dysfunction in patients with juvenile systemic lupus erythematosus.
To determine whether there is an association between the profile of cognitive dysfunction and academic outcomes in patients with juvenile systemic lupus erythematosus (JSLE). Patients aged ≤18 years at the onset of the disease and education level at or above the fifth grade of elementary school were selected. Cognitive evaluation was performed according to the American College of Rheumatology (ACR) recommendations. Symptoms of anxiety and depression were assessed by Beck scales; disease activity was assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI); and cumulative damage was assessed by Systemic Lupus International Collaborating Clinics (SLICC). The presence of autoantibodies and medication use were also assessed. A significance level of 5% (p<0.05) was adopted. 41 patients with a mean age of 14.5±2.84 years were included. Cognitive dysfunction was noted in 17 (41.46%) patients. There was a significant worsening in mathematical performance in patients with cognitive dysfunction (p=0.039). Anxiety symptoms were observed in 8 patients (19.51%) and were associated with visual perception (p=0.037) and symptoms of depression were observed in 1 patient (2.43%). Patients with JSLE concomitantly with cognitive dysfunction showed worse academic performance in mathematics compared to patients without cognitive impairment.


Development and validation of a nomogram to predict the risk of cesarean delivery in macrosomia.
To develop and validate a nomogram that predicts individual probability of cesarean delivery in cases of macrosomia (>4,000 g). The nomogram was built based on the data from 246 patients who delivered macrosomic infants at Conception Hospital (Marseille, France), and was validated on an external population of 206 patients. Logistic regression was used to construct a model to predict the probability of cesarean section. The calculations were based on actual birth weight. The accuracy of the model was evaluated by area under the receiver operator curve. In the multivariate analysis performed on the training set, maternal age (p=0.002), parity (p=0.003), and maternal height <1.65 m (p=0.01) were found to be significantly associated with the occurrence of cesarean delivery and included in the nomogram. The final variables included in the nomogram were: age (p=0.01), maternal height (p=0.02), parity (p<0.001), and previous cesarean section (p=0.009). Area under the ROCs was 0.80 and 0.78 in the training set before and after bootstrapping, respectively, and 0.88 in the validation set. The calibration of the nomogram was good. We have developed a nomogram based on actual birth weight that accurately predicts the risk of cesarean delivery in cases of macrosomia. This tool might be useful for decision-making.


Plasmid pGS5 from the hyperthermophilic archaeon Archaeoglobus profundus is negatively supercoiled.
We present evidence that, in contrast to plasmids from other hyperthermophilic archaea, which are in the relaxed to positively supercoiled state, plasmid pGS5 (2.8 kb) from Archaeoglobus profundus is negatively supercoiled. This might be due to the presence of a gyrase introducing negative supercoils, since gyrase genes are present in the genome of its close relative A. fulgidus, and suggests that gyrase activity predominates over reverse gyrase whenever the two topoisomerases coexist in cells.


Long-Term Outcomes of Endovascular Interventions in More than 500 patients with Budd-Chiari Syndrome.
To assess and compare the long-term outcomes of various endovascular interventions in patients with Budd-Chiari syndrome (BCS). In this single-center retrospective study, 510 consecutive patients with BCS who had undergone a total of 618 endovascular procedures from January 2001 to December 2019 were included. Details of the type of endovascular intervention, technical success, clinical success, patency rate, complications, and survival outcomes were analyzed. The overall technical success rate was 96% (593 of 618 procedures; 500 in treatment-naïve patients and 93 repeat interventions for recurrent disease). Endovascular procedures included recanalization procedures (angioplasty and stent placement) in 355 patients (71%) and transjugular intrahepatic portosystemic shunt (TIPS) creation in 145 (29%). Major postprocedure complications occurred in 14 patients (2.8%). Vascular/stent restenosis occurred in 95 patients (19%), and successful repeat intervention was performed in 82 of those 95 (86.3%). An additional 11 of these 82 (13.4%) underwent a third intervention for restenosis. In the recanalization and TIPS groups, the 1- and 5-y cumulative patency rates were 87% and 74% and 95% and 68%, respectively. The 1- and 5-y survival rates were 96% and 89% and 90% and 76%, respectively. Endovascular interventions for BCS are feasible and safe in the majority of patients, with excellent short- and long-term patency and survival rates.


The role of concurrent chemotherapy and radiation in the management of patients with squamous cell carcinomas of the head and neck.
The management of patients diagnosed with squamous cell carcinomas of the head and neck has undergone a major paradigm shift during the past decade. The current application of systemic therapy and radiation has offered this patient population the opportunity for cure while simultaneously achieving organ preservation. Researchers have focused their efforts on optimizing radiotherapy treatment schedules, defining effective chemotherapy combinations, and investigating novel drug delivery procedures. This article will review the results of the early trials that identified the ability of sequential therapy to achieve organ preservation without sacrificing survival. These studies helped pave the way for the development of concurrent chemoradiation strategies. The results of multiple meta-analyses that have served as the basis for recent multi-institutional, randomized trials will be examined. At the same time, investigators have studied the role of altered fractionation radiotherapy schedules in conjunction with both systemic and intra-arterial chemotherapy. Researchers have long appreciated the differences in outcomes of head and neck tumors based on anatomic location. The results of the Intergroup trial that has helped to define the current national standard of care for this patient group will be reviewed. While most studies conducted to date have used platinum and 5-fluorouracil drug combinations, recent trials have begun to investigate the use of taxane-based regimens. The ability to now target cellular protein receptors has led investigators to focus their interest on the potential role for new biologic agents in combined modality treatment schemes. These treatment regimens hold tremendous promise for improving long-term outcomes while maintaining the quality of life for this patient population.


Simultaneous determination of 222Rn and 220Rn exhalation rates from building materials used in Central Italy with accumulation chambers and a continuous solid state alpha detector: influence of particle size, humidity and precursors concentration.
A method to determine simultaneously the rates of 222Rn and 220Rn released from building materials quarried in Central Italy is presented. The method makes use of a continuous monitor equipped with a solid state alpha detector, in-line connected to a small accumulation chamber. The effects of chamber leakage and back diffusion on 222Rn free exhalation rate is evaluated. The influence of available exhalation surface, humidity content and precursors concentration on radon and thoron exhalation rates is investigated.


Ethanol inhibits ligand-activated Ca2+ channels in human B lymphocytes.
Ethanol reportedly is immunosuppressive, interfering with lymphocyte proliferation. To investigate the basis for this immunosuppression, the effects of acute treatment with ethanol were studied on Ca2+ mobilization in tonsillar B lymphocytes and the human lymphoblastoid B-cell line, Ramos. The level of intracellular Ca2+ was monitored in cells loaded with the fluorescent dye indo-1 following stimulation with either anti-IgM antibody or platelet activating factor. The effect of ethanol was also examined on the induction of the early proto-oncogene c-fos in these cells. Ethanol inhibited ligand-activated Ca2+ mobilization due to transmembrane influx but not intracellular store release, in a dose- and time-dependent manner. This inhibition was not due to the inability of anti-IgM to bind to its surface receptor nor to membrane depolarization induced by ethanol. Ethanol also inhibited the Ca2(+)-dependent induction by anti-IgM of c-fos in these cells. The inhibitory effects of ethanol on ligand-activated Ca2+ channels and subsequent induction of c-fos may provide the basis for its immunosuppressive action.


Immunotherapy of melanoma with BCG: two fatalities following intralesional injection.
Two fatalities are reported following intralesional injection of BCG for immunotherapy of malignant melanoma. In both cases the terminal events were characterized by high fevers, major clotting defects, hypotension, and anuria, suggesting that the mechanism was hypersensitivity to BCG.


Amelioration of obesity-associated inflammation and insulin resistance in c57bl/6 mice via macrophage polarization by fish oil supplementation.
Enormous phenotypic plasticity makes macrophages the target cells in obesity-associated inflammatory diseases. Thus, nutritional components that polarize macrophages toward antiinflammatory phenotype can partially reverse inflammatory diseases like insulin resistance. In the present study, macrophage-polarizing and insulin-sensitizing properties of fish oil (FO) were evaluated in obese insulin-resistant c57bl/6 mice fed high-fat diet (HFD-IR) after oral supplementation with FO (4, 8 or 16mg/kg body weight) and compared to lean and HFD-IR mice. FO-supplemented HFD-IR mice exhibited reduced adiposity index, serum cholesterol and triglycerides and increased insulin sensitization and showed improved adipose tissue physiology under light and transmission electron microscopy. NF-κB/P65 expression showed a downward shift on FO supplementation. The surface marker of M1 macrophages (CD-86) and the TLR-4 expression reduced with the increased supplementation of FO. Expression of arginase 1, an important marker of M2 macrophages, increased in a dose-dependent manner in response to FO dosage, which was observed at protein level by the western blotting and at mRNA level by real-time PCR. The cytokine profile of adipose tissue macrophages showed a steep shift toward antiinflammatory ones (IL-4 and IL-10) from the inflammatory TNF-α, IFN-γ, IL-2 and IL-1β. Thus, macrophage polarization seems to be the plausible mechanism via which FO alleviates obesity-induced inflammation and insulin resistance.


IYOLO-NL: An improved you only look once and none left object detector for real-time face mask detection.
Object detection is a fundamental task in computer vision that aims to locate and classify objects in images or videos. The one-stage You Only Look Once (YOLO) models are popular approaches to object detection. Real-time monitoring of mask wearing is necessary, especially for preventing the spread of the COVID-19 virus. While YOLO detectors facing challenges include improving the robustness of object detectors against occlusion, scale variation, handling false detection and false negative, and maintaining the balance between higher precision detection and faster inference time. In this study, a novel object detection model called Improved You Only Look Once and None Left (IYOLO-NL) based on YOLOv5 was proposed for real-time mask wearing detection. To fulfill the requirement of real-time detection, the lightweight IYOLO-NL was developed by using novel CSPNet-Ghost and SSPP bottleneck architecture. To prevent any missed correct results, IYOLO-NL integrates the proposed PANet-SC with a multi-level prediction scheme. To achieve high precision and handle sample allocation properly, the proposed global dynamic-k label assignment strategy was utilized in an anchor-free manner. A large dataset of face masks (FMD) was created, consisting of 6130 images, for use in conducting experiments on IYOLO-NL and other models. The experiment results show that IYOLO-NL surpasses other state-of-the-art (SOTA) methods and achieves 98.8% accuracy while maintaining 130 FPS.


[Esophageal stenosis caused by carcinomatous mediastinitis secondary to epidermoid carcinoma of the anal canal].
A case of oesophageal stenosis due to mediastinal carcinosis from squamous carcinoma of the anus, treated five years before by radiotherapy, is reported. Radiosensitivity of the tumor ensured a good results with complete resolution.


Role of E-cadherin molecules in spheroid formation of hepatocytes adhered on galactose-carrying polymer as an artificial asialoglycoprotein model.
The role of E-cadherin in the spheroid formation of hepatocytes adhered on the poly(N-p-vinylbenzyl-D-lactonamide) (PVLA) as a model ligand for asialoglycoprotein receptors (ASGP-R) of hepatocytes was studied. Expression of E-cadherin was increased in round hepatocytes adhered on a high-coating density of PVLA (100 microg/ml), and also in flat ones adhered on a low-coating density of PVLA (1 microg/ml) in the presence of epidermal growth factor (EGF). Hepatocyte spheroids formed on the high-coating density of PVLA in the presence of EGF after 48 h were inhibited by an anti-E-cadherin monoclonal antibody (ECCD-1). From immunofluorescence and confocal laser microscopy, E-cadherin was localized in the intercellular boundaries and concentrated at the inside surface of aggregated cells. As a result, E-cadherin could play an important role in hepatocyte assembly.


Investigations on purine and pyrimidine bases stacking associations in aqueous solutions by the fluorescence quenching method. III. Intramolecular association of 9,9'-[1,3-propylene]-bis-2-aminopurine.
General equations relating fluorescence quantum yield and lifetime of a compound with its intramolecular stacking equilibrium and kinetics were derived. Intramolecular stacking association of 9,9'-[1,3-propylene]-bis-2-aminopurine in aqueous solution was examined within the range of temperatures from 0 to 90 degrees C. A two-state thermodynamic model of the association was verified. The stacking enthalpy and entropy can be taken, with a good approximation, as temperature-independent (deltaH equals - 2.0 kcal/mol, deltaS=-3.25 e.u.) although the function deltaG=-0.00886T2 + 8.847 T - 2876 describes more precisely the observed changes of stacking free enthalpy with temperature. The association rate constants were detemined. Activation energy of the reaction (2 kcal/mol) is the same as in the case of association between free 2-aminopurine molecules. It confirms a two-step mechanism of the process. The advantages and shortcomings of the fluorescence quenching method are discussed.


How can a joint European health technology assessment provide an 'additional benefit' over the current standard of national assessments? : Insights generated from a multi-stakeholder survey in hematology/oncology.
We conducted a multi-stakeholder survey to determine key areas where a joint European health technology assessment (HTA) could provide 'additional benefit' compared to the status quo of many parallel independent national and subnational assessments. Leveraging three iterative Delphi cycles, a semiquantitative questionnaire was developed covering evidence challenges and heterogeneity of value drivers within HTAs across Europe with a focus on hematology/oncology. The questionnaire consisted of five sections: i) background information; ii) value drivers in HTA assessments today; iii) evolving evidence challenges; iv) heterogeneity of value drivers across Europe; v) impact of Europe's Beating Cancer Plan (EBCP). The questionnaire was circulated across n = 189 stakeholder institutions comprising HTA and regulatory bodies, clinical oncology associations, patient representatives, and industry associations. N = 30 responses were received (HTA bodies: 9; regulators: 10; patients' and physicians' associations: 3 each; industry: 5). Overall, 17 countries and EU level institutions were represented in the responses. Consistency across countries and stakeholder groups was high. Most relevant value drivers in HTAs today (scale 1, low to 5, high) were clinical trial design (mean 4.45), right endpoints (mean 4.40), and size of comparative effect (mean 4.33). Small patient numbers (mean 4.28) and innovative study designs (mean 4.1) were considered the most relevant evolving evidence challenges. Heterogeneity between regulatory and HTA evidence requirements and heterogeneity of the various national treatment standards and national HTA evidence requirements was high. All clinical and patient participants stated to have been with EBCP initiatives. For a European HTA to provide an 'additional benefit' over the multitude of existing national assessments key methodological and process challenges need to be addressed. These include approaches to address uncertainty in clinical development; comparator choice; consistency in approaching patient-relevant endpoints; and a transparent and consistent management of both HTA and regulatory procedures as well as their interface, including all involved stakeholder groups.


Heat stress delays detoxification of phenanthrene in the springtail Folsomia candida.
Climate change has intensified the occurrence of heat waves, resulting in organisms being exposed to thermal and chemical stress at the same time. The effects of mild heat shock combined with sublethal concentrations of phenanthrene (PHE) on defense mechanisms in springtails Folsomia candida were investigated. The transcription of Heat Shock Protein 70 (HSP70) was significantly upregulated by heat shock but tended to reach the control levels after 42 h of recovery. The transcription of cytochrome P450 3A13 (CYP3A13) was upregulated 3-13 fold by PHE but suppressed by heat shock. The suppression by heat shock might contribute to the reduced detoxification of PHE during high-temperature exposure. In line with this, we found that the internal PHE concentration was approximately 70% higher in heat-shocked springtails than in animals kept at control temperature. In general, the transcription of genes encoding enzymes of detoxification phase Ⅱ (glutathione S-transferase 3) and phase Ⅲ (ABC transporter 1) and the activity of antioxidant defense enzymes (superoxide dismutase and catalase) were less influenced than genes encoding phase I detoxification mechanisms (CYP3A13). These results indicate that heat shock delays the detoxification of PHE in springtails.


Path dependence of adsorption behavior of mixtures containing dipalmitoyl phosphatidylcholine.
The adsorption of aqueous phospholipid dispersions containing dipalmitoyl phosphatidylcholine (DPPC) is investigated at 35-37 degrees C as a function of dispersion preparation technique. Systems studied in terms of surface pressure-time (pi-t) adsorption behavior were pure DPPC, 9:1 DPPC:dipalmitoyl phosphatidylethanolamine, 7:3 DPPC:egg phosphatidylglycerol (PG), and lipids extracted from cow lung lavage. The results show that pi-t characteristics can differ significantly depending on the technique by which the DPPC-containing mixtures are initially dispersed in 0.15 M NaCl solution. Examples of path dependence include the fact that DPPC, which will not adsorb at T = 35 degrees C when placed in powdered crystals on the subphase surface, exhibits measurable pi-t changes after subphase dispersion by sonication or by mechanical vortexing. For 7:3 DPPC:PG, dispersion by sonication on ice or by mechanical vortexing gives faster adsorption than dispersion by sonication without temperature control. The effect of heating to T = 45 degrees C, which is greater than the gel to liquid crystal transition temperature of DPPC (Tc = 41 degrees C), is found to be particularly detrimental to the adsorption of 7:3 DPPC:PG. Of the phospholipid mixtures studied, extracted cow lung lipids exhibited by far the greatest adsorption capability and also showed less path dependence than 7:3 DPPC:PG. Similarly, in terms of dispersion techniques investigated, sonication on ice tended to give the most rapid adsorption for a given phospholipid mixture.


Agarose gel electrophoresis determination of bovine lipoproteins compared with a wet chemistry method.
Quantification of serum lipoproteins provides information relative to the overall metabolic health, degree of lipid mobilization, and hepatic function of dairy cattle. Automated assays performed on benchtop chemistry analyzers and commercially available kits use reagents developed for human lipoproteins. The substantial physical and chemical differences between bovine and human lipoproteins potentially confounds the use of these assays in evaluating bovine lipoproteins. In this study, we prospectively analyzed serum lipoproteins from 56 Holstein cows using horizontal slab agarose gel electrophoresis to semi-quantify the high-density lipoprotein (HDL) and low-density lipoprotein (LDL) fractions by optical densitometry. Ultracentrifugation was used to confirm the electrophoretic separation pattern of the lipoproteins. The values obtained using the electrophoretic method were compared with values obtained by direct measure of HDL cholesterol, total cholesterol, and triglyceride (TG) concentrations on a Roche chemistry analyzer, and calculated LDL cholesterol. Correlation between these methods was poor for HDL (Passing-Bablok regression line: y = 30.31 + 0.853x) and could not be calculated for LDL. Automated HDL values were equal to, or higher than, the total cholesterol concentration in 25 of the 56 samples. The TG concentrations were above the reference interval in 18 samples, and these samples had an average of 96% of the cholesterol measured as HDL by the automated method, and 78% HDL by electrophoresis. Given that it is physiologically impossible to have more cholesterol within the HDL fraction than in the total serum fraction, and the increased proportion of TG found in LDL and very-low-density lipoprotein, our results draw into question the accuracy of the Roche automated assay in quantifying bovine lipoprotein fractions.


Quality of life of children with language delays.
We investigated health-related quality of life (HRQOL) of children with language problems and controls. Data on language development (Language Screening Instrument 3-years-olds, Van Wiechen items) and HRQOL by means of the TNO-AZL Pre-school children Quality of Life-questionnaire (TAPQOL) were collected at age 3 in a population-based cohort by parental questionnaire (n = 8877, response 78%; mean age 39.1 months (SD 2.0), 4347 were girls). Cronbach's alpha (internal consistency) ranged between 0.63 and 0.85. Dependent on the definition of language problem, 131 to 316 children appeared to be language impaired. Receiver Operating Characteristic analyses (ROC-curves) to assess the discriminative ability of six TAPQOL scales revealed that the Communication scale and Social Functioning scale discriminated best between children with language problems and children without these problems. Language-impaired children had significantly lower scores on the Communication scale and Social Functioning scale as compared to children without language problems (p < 0.01). The findings indicate that language problems at age three can have an impact on children's social life. These results provide additional evidence for the importance of monitoring the language development and its consequences during childhood.


A hydraulic behavior of the mucosal structure of the intramural common bile duct. An experimental study.
In the intramural portion of the common bile duct in the dog, the lumen is occluded by the mucosal folds which are pointed to the direction of the ductal orifice. Luminal occlusion by the folds becomes more marked from the halfway of the portion as judged from the duodenal muscle layers. A pressure study using the pressure ramp apparatus suggested that the mucosal structure plays some role in generating the passage resistance to bile floow and in the prevention of regurgitation of duodenal content.


Oral processing effort, appetite and acute energy intake in lean and obese adults.
Chewing reportedly contributes to satiation and satiety signals. Attempts to document and quantify this have led to small and inconsistent effects. The present trial manipulated oral processing effort though required chewing of gums of different hardness and measured appetitive sensations, energy intake, gastric emptying, GI transit time, and concentrations of glucose, insulin, GLP-1, ghrelin and pancreatic polypeptide. Sixty adults classified by sex and BMI (15 each of lean females, obese females, lean males and obese males) were tested in a randomized, controlled, cross-over trial with three arms. They chewed nothing, soft gum or hard gum for 15 min while sipping grape juice (10% of individual energy needs) containing acetaminophen and lactulose on one day each separated by 7 days. Electromyographic recordings and self-reports were obtained during and after chewing to quantify oral processing effort. Blood was sampled through an indwelling catheter and appetite ratings were obtained at baseline and at 0, 15, 30, 45, 60, 90, 120, 180 and 240 min after chewing initiation. Breath samples were collected at 10 min intervals for the first 2h and at 30 min intervals for the next 2h. No effects of chewing were observed for appetitive sensations or gut peptide concentrations. Energy intake tended to decline in lean and increase in obese participants so that daily energy intake differed significantly between the two groups when chewing either gum, while no difference was observed on the non-chewing day. Serum glucose and insulin were significantly lower at selected time points 90-240 min after chewing compared to baseline and the non-chewing day. These data indicate chewing effort does not affect appetitive sensations or gut peptide secretion, but may exert a small differential effect on acute energy intake in lean and obese individuals and lead to greater post-prandial declines of serum glucose and insulin. The efficacy of gum chewing as a substitute for eating for weight management remains uncertain.


A novel water quality data analysis framework based on time-series data mining.
The rapid development of time-series data mining provides an emerging method for water resource management research. In this paper, based on the time-series data mining methodology, we propose a novel and general analysis framework for water quality time-series data. It consists of two parts: implementation components and common tasks of time-series data mining in water quality data. In the first part, we propose to granulate the time series into several two-dimensional normal clouds and calculate the similarities in the granulated level. On the basis of the similarity matrix, the similarity search, anomaly detection, and pattern discovery tasks in the water quality time-series instance dataset can be easily implemented in the second part. We present a case study of this analysis framework on weekly Dissolve Oxygen time-series data collected from five monitoring stations on the upper reaches of Yangtze River, China. It discovered the relationship of water quality in the mainstream and tributary as well as the main changing patterns of DO. The experimental results show that the proposed analysis framework is a feasible and efficient method to mine the hidden and valuable knowledge from water quality historical time-series data.


Lymphocyte subsets associated with T cell receptor beta-chain gene rearrangement in patients with rheumatoid arthritis and neutropenia.
To determine the incidence of a clonal lymphoid disease in patients with chronic rheumatoid arthritis (RA) and neutropenia. Lymphocytes from 23 RA patients with either current neutropenia or a history of this complication were studied. Eight patients had a clonal rearrangement of the T cell receptor beta-chain gene. Phenotypically, they showed a distinctive pattern characterized by an inverted CD4+:CD8+ cell ratio and an increased number and percentage of CD57+/CD8+ and CD3+/DR+ lymphocytes. None had evidence of a lymphoid malignancy. Among RA patients with neutropenia, there is a subset who have a subclinical disease resembling T gamma lymphoproliferative disease.


Effects of diet and folate on levels of micronucleated polychromatic erythrocytes.
We describe a study examining the effects of fried beef consumption on the frequency of micronuclei in RNA-positive polychromatic erythrocytes (PCEs) in humans. 5 splenectomized individuals participated in a 2-week experiment consisting of 3 phases. During the first and last phases the subjects refrained from eating cooked meat for 4-5 days. This was designed to clear their system of mutagens found in cooked-meat products. In the second phase each person ate a similar diet, but also consumed 4 quarter-pound well-done hamburgers per day for 4 days. Erythrocyte-folate levels were also measured for each donor. No association between diet phase and micronucleus frequencies was observed among the 2 subjects with normal levels of folate. However, among the 3 low-folate donors, the frequency of micronucleated PCEs appeared to be associated with diet. Micronucleus frequencies began to increase 1 day following onset of the beef phase, and started to decline 1 day after finishing this phase. These observations are in agreement with erythrocyte maturation kinetics following short-term exposure. A repeat study performed on one of the low-folate donors consisted of two beef phases separated by a vegetarian phase. Beef in one phase was fried (high in mutagenic amino-imidazoazaarenes [AIAs]) while the beef in the other phase was fried after first being microwave-cooked (low in AIAs). Significant increases in the micronucleus frequency were not observed in this experiment, suggesting that AIAs formed during frying were not solely responsible for the induction of micronuclei.


Preoperative Neutrophil-to-Lymphocyte Ratio as a Prognostic Factor in Uterine Sarcoma.
Recent studies have demonstrated that the tumor microenvironment, known to be influenced by inflammatory cells, plays a crucial role in cancer progression and clinical outcome of patients. The objective of the present study was to investigate prognostic values of preoperative neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for disease-free survival (DFS) and overall survival (OS) of uterine sarcoma patients. Ninety-nine patients with uterine sarcoma treated in eight multicenter institutions over the last 20 years were retrospectively analyzed. Curves of DFS and OS were calculated using the Kaplan-Meier method, and univariate and multivariate analyses of various prognostic factors were performed using a Cox proportional hazard regression model. High NLR was significantly associated with worse DFS (p = 0.007) and OS (p = 0.039). Advanced stage (p = 0.017) and high mitotic index (p = 0.036) retained their prognostic significance for DFS. Other clinical variables, including PLR, CA125, and lactate dehydrogenase (LDH) failed to show significant impact. Our findings showed that an elevated preoperative NLR was associated with poor clinical outcome in uterine sarcoma patients. Our results suggest that high NLR in early-stage uterine sarcoma patients might indicate that such patients need more intensive treatments.


Clinical experience with hepatic resection for ruptured hepatocellular carcinoma.
Spontaneous rupture of a hepatocellular carcinoma (HCC) is an uncommon but fatal complication of this disease. Surgical treatment is aimed at controlling the intraperitoneal hemorrhage, which has been achieved by hepatectomy, hepatic arterial ligation, packing and suturing. However, hemostasis obtained by hepatic arterial ligation, packing and suturing is not particularly effective, and the rebleeding rate is high. Information on hepatectomy for ruptured HCC is sparse, and we therefore reviewed our experience with hepatic resection for this potentially fatal complication. The clinicopathological features of 23 patients with ruptured HCC who underwent hepatectomy during the past 15 years were reviewed. Morbidity, mortality and survival rates were analyzed. Effective hemo-stasis was achieved by hepatectomy. Indications for operative treatment were acute abdomen necessitating immediate laparotomy in 12, and spontaneous hemoperitoneum in 11. Types of hepatectomy included left hemihepatectomy in 3, lateral segmentectomy in 6 and local excision in 14. Liver cirrhosis was the concomitant disease in 13 (56.5%). Hospital mortality rate was 4.3%. 1, 2, 3, and 5 year survival rates were 60%, 52%, 40.5% and 26.5%, respectively. Hepatic resection is the treatment of choice for ruptured HCC. Long-term survival can be observed in a few patients without recurrence.


Effects of an integrated approach of hatha yoga therapy on functional disability, pain, and flexibility in osteoarthritis of the knee joint: a randomized controlled study.
The study objectives were to evaluate the efficacy of integrating hatha yoga therapy with therapeutic exercises for osteoarthritis (OA) of the knee joints. This was a prospective, randomized, active controlled trial. Two hundred and fifty (250) participants who had OA knees and who were between 35 and 80 years (yoga 59.56±9.54) and (control 59.42±10.66) from the outpatient department of Ebnezar Orthopedic Center, Bengaluru, were randomly assigned to receive hatha yoga therapy or therapeutic exercises after transcutaneous electrical stimulation and ultrasound treatment (20 minutes per day). Both of the groups practiced supervised interventions (40 minutes per day) for 3 months. One hundred and eighteen (118) (yoga) and 117 (control) subjects were available for the final analysis. There were significant differences within (Wilcoxon's, p<0.001) and between the groups (Mann-Whitney U, p<0.001) on all the variables, with better improvements in the yoga than the control groups. Walking pain in the yoga (37.3%, 64.9%) and control (24.9%, 42%), knee disability in the yoga (59.7%, 83%) and control (32.7%, 53.6%), range of knee flexion in yoga (12.7%, 26.5% right, 13.5%, 28% left) and control (6.9%, 13.3% right, 5.6%, 11.5% left), joint tenderness in yoga (52.3%, 86.1%) and control (28%, 57.1%), swelling in yoga (55.4%, 85.9%) and control (32.1%, 60%), crepitus in yoga (44.0%, 79.9%) and control (27.0%, 47.8%) and walking time in yoga (26.6%, 52.8%) and control (9.3%, 21.6%), all improved more in the yoga than the control groups on the 15th and 90th day, respectively. An integrated approach of hatha yoga therapy is better than therapeutic exercises as an adjunct to transcutaneous electrical stimulation and ultrasound treatment in improving walking pain, range of knee flexion, walking time, tenderness, swelling, crepitus, and knee disability in patients with OA knees.


The health needs of asylum seekers living in the community.
Asylum seekers living in the Australian community, and awaiting the outcome of applications for protection visas, may require medical treatment for a range of illnesses, and are likely to have psychological or musculoskeletal problems as a consequence of traumatic experiences in their own countries. Many require specialist treatment. Some asylum seekers living in the community are denied access to Medicare and can not afford basic medical treatment. This creates suffering in the short term and complications in the long term. Healthcare professionals have an ethical responsibility to provide basic medical care for asylum seekers in Australia.