The effect of restrained eating on acute stress-induced food intake in people with obesity.
Restrained eating, defined as a form of intense dieting or restrictive food intake of specific macronutrients or types of food with sporadic episodes of overeating, results in an increased risk of overweight and obesity. Acute stress situations cause irregular eating patterns and are connected to restrained eating. Therefore, the present study investigates the effect of high/low restrained eating on eating behavior in people with obesity after standardized acute stress induction as well as resting condition. Fifty men and women with obesity (BMI: 33.62 ± 3.93 kg/m2) were categorized into high restrained eaters (HRE) and low restrained eaters (LRE). The total energy intake was measured during a standardized laboratory meal after a resting and stress condition (Trier Social Stress Test) on two separate days. HRE and LRE showed differences in the total energy intake in response to acute stress but not after resting condition (F(1, 47) = 9.188, p = .004, η2 = 0.164). Lower total energy intake after stress compared to resting condition could be observed in HRE (t (23) = -2.617, p = .015). LRE showed higher total energy intake after stress than after resting condition (t (25) = 2.155, p = .041). The present data suggest that restrained eating behavior might be an influencing factor for stress-induced eating in obesity. It is highly necessary to understand the association between restrained eating behavior, acute stress and obesity for the improvement of the behavioral intervention of dietary restriction.


Technical skills examination for general surgical trainees.
The technical skills of surgical trainees are difficult to assess and compare objectively. This study involved a structured, multistation, technical skills examination that enables the stratification of surgical trainees. Twenty-two surgeons (five basic surgical trainees, eight junior specialist trainees, four senior specialist trainees and five consultants) participated in the study. All undertook a five-station technical skills examination consisting of three synthetic simulations (bowel anastomosis, vascular anastomosis, saphenofemoral dissection) and two virtual reality-based (flexible sigmoidoscopy and laparoscopy) assessment stations. Video-based analyses and in-built computer scoring were used to measure each surgeon's performance. The mean rank was determined for each variable, and the sum of the mean ranks produced a total score. There was a significant improvement in overall performance with increasing seniority (P<0.001). Significant differences were observed between basic surgical trainees and junior specialist trainees (P=0.019), and between junior and senior specialist trainees (P=0.048), but not between senior trainees and consultants. This examination successfully differentiated surgical skill, both between surgeons with different grades of experience and within the target study group of specialist trainees. The examination is feasible in terms of the timeframe needed to complete tasks, cost, and efficiency in performing video-based assessments.


Hydroxyapatite-polyethylene composites for bone substitution: effects of ceramic particle size and morphology.
Synthetic hydroxyapatite particles of two median sizes and different morphologies have been used to manufacture hydroxyapatite reinforced high density polyethylene composites (HAPEX) for medical applications. The effects of hydroxyapatite particle size on properties of the resultant composites were investigated using various techniques. It was found that composites with smaller hydroxyapatite particles had higher torsional modulus, tensile modulus and tensile strength, but lower strain to failure. Examination of fracture surfaces revealed that only a mechanical bond existed between the filler and the matrix. It was shown that dynamic mechanical analysis is useful in studying the viscoelastic behaviour of the composite.


A comparative study of serum Zn, Cu, Mg, Mn, Cr, and Fe levels and their association with the vulnerability of Iraqi COVID-19 patients.
For the immune system to protect the body from infectious diseases such as COVID-19, it needs the ideal amount of vital trace elements. Trace element levels, especially, zinc (Zn), copper (Cu), magnesium (Mg), manganese (Mn), chromium (Cr), and iron (Fe) levels, may affect how sensitive an individual is to COVID-19 and other viruses. The current study evaluated the level of those trace elements during stays in the isolation center and investigated their association with vulnerability to COVID-19. A total of 120 individuals, 49 males and 71 females aged between 20 and 60 years, were included in this study. Forty individuals infected with COVID-19, 40 individuals who had recovered from it, and 40 healthy individuals, were all evaluated and studied. By using a flame atomic absorption spectrophotometer, levels of Zn, Cu, and Mg were assessed for all samples, whereas levels of Mn, and Cr were determined by a flameless atomic absorption spectrophotometer. The infected individuals had significantly lower levels of Zn, Mg, Mn, Cr, and Fe than recovered individuals and healthy control individuals (P < 0.0001). On the other hand, the total number of infected patients was found to have much higher levels of Cu than those in the recovered group and the control group. For the recovered and healthy control groups, no significant differences were observed in the levels of trace elements (P > 0.05), except for Zn (P < 0.01). Also, the findings indicated no association of trace elements with age and BMI (P > 0.05). These results show that an imbalance in the levels of essential trace elements could be associated with increasing the risk of COVID-19 infection. However, additional thorough research of greater scope is required considering the severity of the infection.


Effect of Quinapril on the Circadian Blood Pressure Pattern Evaluated by Periodic Analysis of Covariance.
The effects of quinapril on casual blood pressure (BP) and circadian variations in 24-h blood pressure (24ABPM) were studied in patients with essential hypertension. Twenty-six patients were enrolled in the study (mean age 59 plus minus 11 years). After a 4-week washout period, patients, were treated with quinapril 5 mg, 10 mg, or 20 mg once a day until casual blood pressures become optimal within 8--10 weeks. The 24ABPM was performed before and after treatment at 30-min intervals using an ABPM-630 in patients during usual daily activities on the work days. Measured BP was fitted to a periodic regression curve with 24-h and 12-h harmonics. Quinapril significantly decreased casual blood pressure but had no effect on pulse rate. It exhibited an excellent antihypertensive effect throughout 24 h; this effect, however, was stronger during the day than at night, resulting in no excessive nocturnal hypotension. The level of the periodic regression curves for systolic and diastolic blood pressures was significantly decreased following treatment but that of the pulse rate was not affected by this drug. The drug caused changes in the pattern of the periodic regression curve for blood pressure and pulse rate. This was attributed to the more prominent antihypertensive effect of quinapril in the afternoon and evening. To evaluate the efficacy of this drug semiquantitatively, the hyperbaric indices were compared before and after the treatment, and those indices for both systolic and diastolic blood pressures were significantly decreased. Adverse effects occurred in four patients (15.4%), all of which were mild and thought to be clinically insignificant. It was concluded that quinapril, 5--20 mg day(minus sign1), was considered to be useful for patients with mild to moderate essential hypertension.


An In Vitro Differentiation Protocol for Human Embryonic Bipotential Gonad and Testis Cell Development.
Currently an in vitro model that fully recapitulates the human embryonic gonad is lacking. Here we describe a fully defined feeder-free protocol to generate early testis-like cells with the ability to be cultured as an organoid, from human induced pluripotent stem cells. This stepwise approach uses small molecules to mimic embryonic development, with upregulation of bipotential gonad markers (LHX9, EMX2, GATA4, and WT1) at day 10 of culture, followed by induction of testis Sertoli cell markers (SOX9, WT1, and AMH) by day 15. Aggregation into 3D structures and extended culture on Transwell filters yielded organoids with defined tissue structures and distinct Sertoli cell marker expression. These studies provide insight into human gonadal development, suggesting that a population of precursor cells may originate from a more lateral region of the mesoderm. Our protocol represents a significant advance toward generating a much-needed human gonad organoid for studying disorders/differences of sex development.


Compartmental differences of circulating tumor cells in colorectal cancer.
The prognostic role of circulating tumor cells (CTCs) has been established for colorectal cancer (CRC). We investigated the qualitative and quantitative detection of CTC in the central (CVBC) and mesenteric (MVBC) venous blood compartments to elucidate the patterns of hematogenous tumor cell dissemination in patients with CRC. A total of 200 patients were enrolled prospectively. Blood samples were collected from the tumor-draining vein and via a central venous line. CTCs were detected and quantified by using the CellSearch system. Factors associated with CTC detection in both compartments were analyzed by using univariate and multivariate analyses. CTC analyses were performed in the CVBC and MVBC in 200 and 80 patients, respectively. CTCs were found at a higher rate (P=0.01) and at a higher count (P=0.006) in the MVBC compared with the CVBC. On multivariate analyses, stage IV disease (odds ratio, 3.83; 95% confidence interval, 1.42-10.35) and increased preoperative carbohydrate antigen 19-9 level (odds ratio, 3.57; 1.30-9.79) were associated with CTC detection in the CVBC. CTCs were detected more frequently (P=0.05) and at higher numbers (P=0.05) in the CVBC of patients with low compared with mid or high rectal tumors. The qualitative and quantitative detection of CTCs is higher in the MVBC compared with the CVBC of patients with CRC.


The Piezo Mechanosensitive Ion Channels: May the Force Be with You!
Piezo1 and Piezo2 are critically required for nonselective cationic mechanosensitive channels in mammalian cells. Within the last 5 years, tremendous progress has been made in understanding the function of Piezo1/2 in embryonic development, physiology, and associated disease states. A recent breakthrough was the discovery of a chemical opener for Piezo1, indicating that mechanosensitive ion channels can be opened independently of mechanical stress. We will review these new exciting findings, which might pave the road for the identification of novel therapeutic strategies.


Impact of particulate pollution on aquatic invertebrates.
A serious global problem, air pollution poses a risk to both human and environmental health. It contains hazardous material like heavy metals, nanoparticles, and others that can create an impact on both land and marine environments. Particulate pollutants, which can enter water systems through a variety of ways, including precipitation and industrial runoff, can have a particularly adverse influence on aquatic invertebrates. Once in the water, these particles can harm aquatic invertebrates physically, physiologically, and molecularly, resulting in developmental problems and multi-organ toxicity. Further research at the cellular and molecular levels in numerous locations of the world is necessary to completely understand the impacts of particle pollution on aquatic invertebrates. Understanding how particle pollution affects aquatic invertebrates is vital as the significance of ecotoxicological studies on particulate contaminants increases. This review gives a comprehensive overview of the current understanding of how particle pollution affects aquatic invertebrates.


Prevalence of HIV risk behaviors among undocumented Central American immigrant women in Houston, Texas.
Undocumented Central American immigrants in the United States are disproportionately affected by HIV infection. However, epidemiological data on sexual behaviors among undocumented women are sparse and the extent to which behaviors vary by duration of residence in the U.S.is largely unknown. In 2010, we used respondent driven sampling to conduct an HIV behavioral survey among Central American immigrant women residing in Houston, Texas without a valid U.S. visa or residency papers. Here we describe the prevalence of sexual risk behaviors and compare recent (5 years or less in the U.S.) and established immigrants (over 5 years in the U.S.) to elucidate changes in sexual risk behaviors over time. Our data suggest that recent immigrants have less stable sexual partnerships than established immigrants, as they are more likely to have multiple and concurrent sexual partnerships, as well as partnerships of shorter duration.


An 88-year-old woman diagnosed with adrenal tumor and congenital adrenal hyperplasia: connection or coincidence?
An 88-yr-old woman presented with a 3x4x5 cm adrenal incidentaloma. Apart from partial cortisol deficiency there were no clinical or laboratory signs of abnormal hormone production. Because of suspicion of carcinoma, a urinary steroid profile was carried out which indicated 21-hydroxylase deficiency with elevated pregnantriol. Biopsy of the tumor showed benign adenoma tissue. The genetic analysis showed two mutations in the CYP21-gene, V281L and 1172N consistent with mild non-classic congenital adrenal hyperplasia (CAH). The patient showed a general improvement with a low prednisolone dose. Previous reports have shown increased prevalence of CAH in patients with adrenal tumors although, to our knowledge, no one has reported the combination in a patient as old as in ours. Thus, clinical signs and symptoms of CAH should be looked for in patients with adrenal incidentalomas, even in the very old ones, and if suspicion further diagnostic work-up should be carried out to provide adequate treatment and follow-up.


Kinetic evidence for cooperative binding of two ortho-phenanthroline molecules to astacus protease during metal removal.
Kinetic evidence is presented that introduces a new possibility for a mechanism of metal removal from a protein by a chelator. Astacus protease is a 22,614 dalton zinc-metalloendopeptidase from the digestive tract of the freshwater crayfish. Recent studies have shown that it contains a single zinc atom and that removal of this metal yields inactive apo-enzyme, which can be reactivated upon readdition of zinc, cobalt, or copper. The enzyme is inactivated by metal chelators in a time and concentration dependent manner. The inactivation of Zn-Astacus protease by 1,10-phenanthroline (OP) can be monitored continuously in the presence of substrate. The concentration of substrate was found to have no effect on the inactivation rate, indicating that the chelator binding during inactivation is of the noncompetitive type. First-order rate constants for the inactivation process are seen to depend on the concentration of chelator in a sigmoidal manner. Based on mathematics analogous to that for cooperativity in enzyme-substrate kinetics, the deduction is made that there are two OP binding sites on the protein and that the rate of inactivation is related to the saturation of both sites with ligand. If one uses this model, the limiting rate constant of inactivation upon saturation of both sites with ligand is 6.76 x 10(-3) sec-1, and the half maximal rate occurs at an OP concentration of 6.52 mM. A mechanism is proposed wherein both protein bound chelators can cooperate during metal removal either by direct chelation of the metal or by allosteric means. The proposed model and the noncompetitive binding of chelator and substrate are discussed in relation to a recently proposed metal binding site.


Fibroblast growth factor 9: cloning and immunolocalisation during tooth development in Didelphis albiventris.
There are no reports in literature about functional roles of fibroblast growth factor 9 (FGF-9) in tooth development in animals with complete tooth pattern. The classical model for studying tooth development is the mouse, which has small number of teeth and distinctive incisor and molar patterns. The opossum Didelphis albiventris with five upper and four lower incisors, one canine, three premolars, and four molars, on each side of the jaw, seems to be a convenient model to test results obtained in the mouse. Molecular expression studies indicate that FGF-9 participates in murine tooth initiation and regulation of morphogenesis. Searching for similarities and differences in FGF-9 expression between the opossum and the mouse, amino acid sequence and expression pattern of FGF-9 in the developing first molars of D. albiventris were characterised. FGF-9 cDNA sequence was obtained using RT-PCR and expressed in bacterial system for recombinant protein production and analysis of immunoreactivity. FGF-9 expression during tooth development was investigated by immunoperoxidase method. FGF-9 protein consists in a 209-residue polypeptide with a predicted molecular mass of 23.5 kDa. FGF-9 amino acid sequence has 98% of sequence identity to human and 97% to rodents. During tooth development, epithelial FGF-9 expression was seen at the dental lamina stage. Mesenchymal expression was seen at the bud stage and at the cap stage. No significant expression was found in the enamel knot. While in rodents FGF-9 is involved in initiation and regulation of tooth shape, it is suggested that it is only involved in tooth initiation in D. albiventris.


General surgeons and clinical ethics: a survey.
To determine the preoccupation of general surgeons concerning ethics. A survey by questionnaire. One thousand members of the Canadian Association of General Surgeons were surveyed through a questionnaire, which inquired about the influence of ethics in their clinical practices. The questionnaire contained 12 questions. There was no recall for those who did not respond. Responses to questions concerning the sex of the respondents, location of practice, number of years in practice, the presence of hospital support, surgeons' interest in ethical issues, use of autonomy, beneficence, nonmaleficence and justice in solving ethical dilemmas and level of education in clinical ethics. Men made up 95% of the respondents; 64% of respondents had been in practice more than 16 years; 58% came from a community or regional hospital; only 10% had no interest in clinical ethics; only 3% stated that they experienced no ethical problems in their practices; and 52% had no formal education in ethics. There was general sensitivity for clinical ethics but an evident lack of formal education and of the presence of ethics committees and ethics consultants in many hospitals.


Natural killer cell activity during mouse hepatitis virus infection: response in the absence of interferon.
The ability of the JHM3 strain of mouse hepatitis virus (MHV) to induce natural killer (NK) cells was examined. Infection of C57BL/6 (B6) mice with this virus resulted in the augmentation of natural cytotoxicity against YAC-I target cells in the absence of a detectable interferon response. The cells responsible for this increased cytotoxicity were sensitive to complement-mediated lysis with an anti-Q-5 reagent but not with a Thy 1.2 antiserum, indicating that they possess an NK-like surface phenotype. Although variation in the NK response of individual B6 mice following JHM virus infection was found, even the animal with the most responsive NK cell population had no detectable interferon in the spleen. This finding contrasted with observations with an unrelated virus (lymphocytic choriomeningitis virus) and a serologically related strain of MHV. Infection with both of these viruses induced augmented NK cell activity and interferon responses. In addition, we found that neither the ability to mount an augmented NK cell response nor preferential lysis of virus-infected targets correlated with resistance or susceptibility to JHM virus infection.


Fibronectin in tears following surgical trauma to the eye.
The concentration of the high molecular glycoprotein fibronectin (FN) was measured by an enzyme-linked immunoadsorbent technique (ELISA) in tears of 25 patients before and after cataract extraction. Both native and degraded FN was measured. The median concentration of FN in tears before surgery was 0.28 mg/l (range: 0.1-3.8 mg/l) and 0.18 mg/l (range: 0.1-1.95 mg/l for degraded and native FN, respectively. The time course of the median values of both types of FN during the post-operative observation period described a biphasic curve with peaks at the second and fifth day following operation. On the twelfth day the concentration of degraded and native FN had almost reached pre-operative levels. The variation in the post-operative FN concentration proved statistically significant. The biological significance of the changes in FN level in the post-operative period is not obvious; the first peak may be explained by a spill-over from plasma, and the second peak may reflect FN production from fibroblasts in the granulation tissue of the corneoscleral cicatrix.


Effect of light-adaptation on the photoreaction of bacteriorhodopsin from Halobacterium halobium.
Light-induced formation of the 410 nm intermediate was investigated on dark-and light-adapted bacteriorhodopsin. The amplitude of the light-induced absorption increase at 410 nm of the light-adapted bacteriorhodopsin was twice as large as that of the dark-adapted bacteriorhodopsin. The amount of protons released from bacteriorhodopsin in response to illumination was also enhanced by light-adaptation. The degree of the enhancement was independent of the temperature in the dark-adaptation. The relation between these photochemical events and the isomeric configurations of retinal is discussed.


Utility of the signal-averaged electrocardiogram in patients presenting with sustained ventricular tachycardia or fibrillation while on an antiarrhythmic drug.
The utility of the signal-averaged electrocardiogram (SAECG) for predicting ventricular tachycardia (VT) induction in patients presenting with sustained VT or ventricular fibrillation (VF) while on an empirically chosen antiarrhythmic agent was assessed in 17 patients. At the time of presentation with a malignant arrhythmia, 12 patients were taking quinidine, three patients were taking procainamide, and two patients were taking flecainide. All patients underwent programmed ventricular stimulation when not taking antiarrhythmic drugs; 12 patients had no inducible sustained VT and five patients had inducible sustained monomorphic VT. The SAECG done in the control state without antiarrhythmic agents was negative for late potentials in 11 of 12 patients in the noninducible group and positive for late potentials in four of five patients in the inducible group (sensitivity = 80% and specificity = 92%). We conclude that in patients presenting with life-threatening ventricular arrhythmias while taking an antiarrhythmic drug, the SAECG distinguishes patients with possible proarrhythmic events from those who have the substrate for inducible sustained VT.


The association between lead contamination on the hand and blood lead concentration: a workplace application of the sodium sulphide (Na2S) test.
Lead is one of the major causes of workplace poisoning and lead contamination on skin is a possible route of lead absorption. Using a colourimetric method with sodium sulphide (Na2S), we examined whether the lead on skin represents longer-term lead exposure. This cross-sectional study of 119 lead-handling workers in a battery recycling plant in Japan was conducted in July 2004. The main outcome measure was skin-colour darkening on the workers' hands, visualised by wetting the seemingly clean hands of the workers with 1% Na2S solution (128 mmol/L): the Na2S test. This study then examined the relationships between the Na2S test results and workers' blood lead concentration (BLC) and hygiene activities. The Na2S test produced skin-colour darkening of the hands of 92 (77%) of the lead workers, although 88 of them had washed their hands with soap and 50 had bathed before taking the test. In the bivariate analyses, a positive result in the Na2S test was associated with not washing hands (p=0.009), not bathing (p=0.061), and a higher BLC (p=0.008). The association between the results of the Na2S test and BLC was still significant in the multivariate linear regression analysis adjusted for age and hand washing (p<0.001). Lead contamination on workers' hands, otherwise unapparent, was clearly demonstrated by the Na2S test. The result of this test was associated with BLC in addition to the hygiene activities after the last work with lead. As the lead contamination on the hand is persistent, simply encouraging hand washing may not be sufficient to reduce lead intake into body.


Long-term health-related quality of life after spontaneous nontraumatic subarachnoid hemorrhage: self and proxy reports in a 10-year period.
This study sought to examine health-related quality of life several years after spontaneous nontraumatic subarachnoid hemorrhage. Recent studies report impairments to be improved as far as normal levels. We question such an improvement in our own patient population over a period of 10 years. The Medical Outcomes Study 36-Item and Medical Outcomes Study 12-Item Short-Form Health Surveys on health-related quality of life were used to question 236 patients and 235 proxies. The patients were assigned to 5 groups according to the time that had elapsed since their hemorrhage: 1 year N = 22, 2 years N = 36, 5 years N = 86, 8 years N = 61, and 10 years N = 31. Analyses of variance (ANOVA, Kruskal-Wallis) and correlation (Spearman, Kendall tau) were used in an exploratory approach. Significance was established as P ≤ 0.05. Over a period of 10 years, health-related quality of life is found to be impaired, and is reported as such by the patients themselves and their proxies. Comparison of the mean values between the groups, ie, 1, 2, 5, and 10 years, revealed no significant differences in health-related quality of life. The calculations with a view to correlations between the group means and time since hemorrhage also produced only very weak correlations of no significance. Health-related quality of life is impaired over a period of 10 years. Spontaneous nontraumatic subarachnoid hemorrhage should be regarded as a chronic cerebrovascular condition.


Effects of postprandial hyperlipemia on the vitamin E content of lipoproteins. GERBAP section Lipoprotéines. Groupe d'Evaluation et de Recherche de l'Assistance Publique des Hôpitaux de Paris.
Delayed postprandial clearance of triglyceride-rich lipoproteins (TGRL) could induce a decrease of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) vitamin E content through its transfer into TGRL. We thus studied lipoprotein vitamin E content during postprandial hypertriglyceridemia induced by a high fat meal without vitamin E supplement. Venous blood was drawn from five healthy male volunteers following a 12 h fast at (t0) then 2 h (t2), 4 h (t4), 6 h (t6) and 8 h (t8) after a 80 g fat meal. In plasma, only TG significantly varied during the postprandial period with a large interindividual variability. Mean composition of lipoproteins in terms of mass was not significantly modified. The amount of vitamin E significantly increased in TGRL and decreased in LDL plus HDL at t4 and t6 relative to t0. Vitamin E content of TGRL and LDL but not of HDL decreased significantly at t4. The mean decrease was 20% (range 5%-54%) for the LDL. LDL- and HDL vitamin E content correlated inversely with plasma TGRL levels. Our data suggest that LDL from subjects with delayed chylomicron clearance could be less protected against oxidation.


Morphology and ultrastructure of the adrenal gland in Bactrian camels (Camelus bactrianus).
In the present study, we examined the morphological features of the adrenal gland in Bactrian camel by means of digital anatomy, light and electron microscopy. Our findings testified that the gland was divided into three parts, capsule, cortex and medulla from outside to inside as other mammals, and the cortex itself was further distinguished into four zones: zona glomerulosa, zona intermedia, zona fasciculate and zona reticularis. Notably, the zona intermedia could be seen clearly in the glands from females and castrated males, whereas it was not morphologically clear in male. There was a great deal of lipid droplets in the zona fasciculate, while it was fewer in the zona glomerulosa and zona reticularis. The cytoplasm of adrenocortical cell contained rich mitochondria and endoplasmic reticulum. The adrenal medulla was well-developed with two separations of external and internal zones. The most obvious histological property of adrenal medulla cells were that they contained a huge number of electron-dense granules enveloped by the membrane, and so medulla cells could be divided into norepinephrine cells and epinephrine cells. Moreover, the cortical cuffs were frequently present in adrenal gland. Results of this study provides a theoretical basis necessary for ongoing investigations on Bactrian camels and their good adaptability in arid and semi-arid circumstances.


Efficacy and safety of a novel paclitaxel-nano-coated balloon for femoropopliteal angioplasty: one-year results of the EffPac trial.
Although paclitaxel drug-coated balloon (DCB) angioplasty is an established endovascular treatment for peripheral artery disease, restenosis remains a major concern. Thus, we compared a novel paclitaxel-coated DCB with nano-coating technology with uncoated plain old balloon angioplasty (POBA). This multicentre trial randomly assigned 171 patients with stenotic and occlusive lesions of the femoropopliteal artery to angioplasty with a novel DCB or uncoated POBA. The primary endpoint, late lumen loss at six months, was 0.92 mm lower in the DCB group (95% CI: -1.36 to -0.49 mm, p<0.001). Patients showed improved walking after DCB treatment at six months (p=0.021). In the DCB group, 44.6% and 50% of the patients improved by three Rutherford-Becker classification stages after six to 12 months, respectively (POBA: 27.8% and 36.8%, respectively). Only one patient needed TLR (1.3%) in the DCB group, compared to 14 patients (18.7%) in the POBA group after 12 months (relative risk [RR]=0.08, 95% CI: 0.01-0.53, p<0.001). Primary patency was 90.3% (DCB group) versus 65.3% (POBA group) after 12 months (RR=1.38, 95% CI: 1.14-1.67, p<0.001). The novel DCB was effective and safe for inhibiting restenosis. Moreover, it demonstrated a better improvement in walking than POBA and showed no mortality concerns due to paclitaxel application after 12 months. Clinical Trials Identifier: NCT02540018


Mitochondrial encephalomyopathy. A variant with heart failure and liver steatosis.
We report the clinical and autopsy findings in a young man of 18 with a chronic progressive disorder comprised of lactic acidosis, mental deterioration, and epileptic seizures which were sometimes accompanied by stroke-like episodes with transient hemiparesis and cortical blindness. He died of congestive heart failure. The autopsy showed lesions of the gray matter of the brain. Both the putamen and parieto-occipital cortex showed loss of neurons and proliferation of macrophages, astrocytes and vessels. There was marked loss of neurons in the inferior olives, and slight reduction of the number of Purkinje cells. Skeletal muscle studies revealed ragged-red fibers and structurally abnormal mitochondria. The heart was enlarged: accumulations of mitochondria occurred in the muscle fibers. The liver exhibited marked fatty degeneration. Biochemical analyses showed normal activities of pyruvate dehydrogenase in thrombocytes, pyruvate carboxylase in lymphocytes, biotinidase in serum as well as succinate dehydrogenase and cytochrome c oxidase. The features of this disorder differ in many respects from cases of mitochondrial encephalomyopathy previously reported and cannot be assigned to any specific disease entity.


Ethics in pediatric end-of-life care: a nursing perspective.
Care of children at the end of life frequently involves ethical dilemmas and difficult decisions. These ethical dilemmas often complicate the already challenging circumstances surrounding the death of a child; therefore, the knowledge and application of ethical principles becomes an essential component of nursing practice. The purpose of this article is to describe bioethical principles and common ethical dilemmas faced by nurses in pediatric end-of-life care and suggest nursing interventions to promote a peaceful end-of-life experience for the child and family.


Accuracy of soft tissue prediction in surgery-first treatment concept in orthognathic surgery: A prospective study.
The purpose of this study was to provide a quantitative accuracy assessment of soft tissue predictions generated by a computer-aided maxillofacial planning system in patients undergoing orthognathic surgery following the "surgery-first" treatment. For this study, we looked at 16 patients with open bite dentofacial-dysmorphosis who underwent orthognathic surgery. Surgeries were planned using conventional sketches and the newly developed computer-assisted SOTIRIOS planning software (developed by the authors). Validation procedures were performed in the following steps: (1) Standardized registration of the pre- and postoperative CT volumes; (2) Automated adjustment of the bone-related preoperative planning to the actual postoperative bony displacement; (3) Simulation of soft tissue changes according to the definitive bony movements; and (4) Calculation of soft tissue differences between the predicted and the actual 6-month postoperative results by distance mapping. The program produced a clinically satisfactory 3D soft tissue prediction, with a mean error of 1.46 mm ± 1.53 mm. The program was suitable for use in virtual surgical planning without technical assistance. This study shows that the program is quite accurate, enabling the surgeon to predict the outcome of the soft tissue. This has the potential to promote the routine application of the surgery-first approach in patients suffering from open bite.


Serum lipids before and after parathyroidectomy in patients with primary hyperparathyroidism.
Eight males and 36 females with hypercalcaemia were operated upon for primary hyperparathyroidism and parathyroid adenomata were revealed in every case. The serum levels of cholesterol and triglycerides were determined before the operations and 6,12 and 18 months after them. Furthermore, the serum lipids of the patients were compared with those of a normacalcaemic sex- and age-matched control group. The serum cholesterol concentration in primary hyperparathyroidism was about 8-10% lower in both females and males compared with the correspondeing control cases and the levels of serum trigycerides were about 22% and 60% lower. After operation the serum cholesterol concentration returned to a normal level and the triglycerides nomalized. The results are discussed in the light of present knowledge about dietary calcium intake, primary hyperparathyroidism and lipid metabolism.


New corneal neovascularization model in rabbits for angiogenesis research.
To evaluate a new experimental model of suture-induced corneal neovascularization (NV) for angiogenesis research. The new model was created in the right eye of 20 New Zealand rabbits using 5 interrupted silk sutures following an inverted triangle pattern. At different time points after suture placement, calibrated photographs were taken to quantify the corneal surface covered by the sutures (SCS) and the corneal NV response. At the end of the experiment, the corneas were processed for histological study. Vascular sprouts were already observed on the 3rd day. On the 7th day, the mean corneal NV surface was 19.02 ± 4.65 mm(2). On the 14th day, the mean corneal NV surface increased up to 28.96 ± 6.33 mm(2), representing 112.18% of the SCS and 21.04% of the total corneal surface. Histological sections showed that the new vessels were located at the two anterior thirds of the corneal stroma with an intense inflammatory infiltration. Our results indicate that this experimental model is effective, reliable and reproducible to induce corneal NV for angiogenesis research.


Comparative bioavailability of two commercial preparations of carbamazepine tablets.
A comparative bioavailability study was performed using two commercially available types of carbamazepine tablets, by statistical analysis of serum levels and other bioavailability parameters. After single oral dose the extent of absorption from the two preparations was similar, although a statistically significant difference in absorption rates was observed. In a multiple-dose study no significant difference in serum carbamazepine levels was found, so the tablets could be considered as bioequivalent drug products.


Stressful life events and adolescent suicidality: An investigation of the mediating mechanisms.
While a number of studies have found an association between stressful life events and adolescent suicidality, underlying mechanisms linking the two continue to be inadequately understood. Drawing upon the stress process, general strain, and support deterioration theories, this study examined the relationship between stressful life events and suicidality in U.S. adolescents, focusing on the mediating roles of depression, substance use, and perceived social support. The data came from the first two waves of the National Longitudinal Study of Adolescent to Adult Health (N = 12,801; M age = 15 at Wave I; 50.2% female). Mediation analyses were performed using the Karlson-Holm-Breen (KHB) method developed for nonlinear probability models. Depression, substance use, and perceived social support accounted for a substantial part of the effect of stressful life events on suicidal ideation (57%) and attempts (43%). All mediating effects were statistically significant. Depression was a relatively stronger mediator for both suicidal outcomes. Significant relationships among stressful life events and suicidal outcomes persisted even after adjusting for the proposed mediators. Stressful life events increase suicidality in adolescents, partly by increasing psychological distress and eroding perceived social support. Findings underscore the necessity of continued emphasis on stress management and support programs in reducing suicidality among vulnerable adolescents exposed to these types of occurrences.


Intravascular ultrasound-factors associated with slow flow following rotational atherectomy in heavily calcified coronary artery.
Intravascular ultrasound (IVUS) can provide useful information in patients undergoing complex percutaneous coronary intervention with rotational atherectomy (RA). The association between IVUS findings and slow flow following rotational atherectomy (RA) has not been investigated, although slow flow has been shown to be an unfavorable sign with worse outcomes. The aim of this study was to determine the IVUS-factors associated with slow flow just after RA. We retrospectively enrolled 290 lesions (5316 IVUS-frames) with RA, which were divided into the slow flow group (n = 43 with 1029 IVUS-frames) and the non-slow flow group (n = 247 with 4287 IVUS-frames) based on the presence of slow flow. Multivariate regression analysis assessed the IVUS-factors associated with slow flow. Slow flow was significantly associated with long lesion length, the maximum number of reverberations [odds ratio (OR) 1.49; 95% confidence interval (CI) 1.07-2.07, p = 0.02] and nearly circumferential calcification at minimal lumen area (MLA) (≥ 300°) (OR, 2.21; 95% CI 1.13-4.32; p = 0.02). According to the maximum number of reverberations, the incidence of slow flow was 2.2% (n = 0), 11.9% (n = 1), 19.5% (n = 2), 22.5% (n = 3), and 44.4% (n = 4). In conclusion, IVUS findings such as longer lesion length, the maximum number of reverberations, and the greater arc of calcification at MLA may predict slow flow after RA. The operators need to pay more attention to the presence of reverberations to enhance the procedure safety.


Design and development of a training video for Accredited Social Health Activists (ASHAs) on brief psychological intervention for depression.
Depression poses a major public health burden and has a large treatment gap in India. The study attempts to address this treatment gap by developing a training video for Accredited Social Health Activists (ASHAs), who are community health workers, on brief psychological intervention for depression. The systematic steps utilized in the design and development of the training video on depression were: 1) Content development of the video script and training booklet for ASHAs based on the review of research literature and two Focus Group Discussions, 2) Mental Health Professionals' evaluation of the video script and training booklet for ASHAs, 3) Translation from English to Kannada, 4) ASHAs' evaluation of the video script and training booklet for ASHAs, 5) Conversion of the video script into a 'shooting script', 6) Video production, 7) Evaluation of the training video, 8) Post-production of the training video, and 9) Development of the training guide. The training video titled "Light of Hope: A Training Video on Depression" was developed along with two training booklets, which are complementary resource materials, for ASHAs and the training Facilitators. The brief psychological intervention for depression elucidated in the training video incorporates the evidence-based strategies of Psychoeducation, Activity Scheduling, Problem-Solving Skills Training, and Diaphragmatic/Abdominal Breathing Skills Training. The study demonstrates the systematic approach that can be employed for the design and development of a mental health training video, which has evidence-based content, incorporates stakeholders' evaluative perspectives, and is culturally contextualized.


Occurrence of fumonisins in maize imported into Iran during 2001-2002.
Fumonisins, fungal toxins found primarily in maize and produced by various Fusarium species, have been shown to cause a variety of significant adverse health effects in livestock and experimental animals, and are probable human carcinogens. Thirty-three maize samples were collected at ports from bulk shipments, which were imported into Iran from six countries during 2001-2002, and analysed by HPLC for the most abundant of the naturally occurring fumonisin analogues, namely fumonisins B1 (FB1), B2 (FB2) and B3 (FB3). Of the 33 samples, 21 (64%) were found to contain FB1 (58-512 μg/kg) at levels above 10 μg/kg. The frequency of FB1 found in maize samples imported from Uruguay and Canada was 75%, followed by China and Argentina (67%), USA (60%), and Brazil (50%). The average FB1 level was 266 and 169 μg/kg for positive and all samples, respectively. Medians were 250 and 146 μg/kg for positive and all samples, respectively. FB2 levels ranged from not detected (<10 μg/kg) to 53 μg/kg, whereas no sample had an FB3 level above the detection level (10 μg/kg). This is the first report of fumonisin contamination of imported maize in Iran. Although, the level of all detected fumonisins were below the Iranian and FDA tolerance levels for foods and feeds, It is necessary to maintain the strict rules to ensure continued safety of imported maize.


Diabetes to Go-Inpatient: Pragmatic Lessons Learned from Implementation of Technology-Enabled Diabetes Survival Skills Education Within Nursing Unit Workflow in an Urban, Tertiary Care Hospital.
Diabetes survival skills education (DSSE) focuses on core knowledge and skills necessary for safe, effective, short-term diabetes self-care. Inpatient DSSE delivery approaches are needed. Diabetes to Go (D2Go) is an evidence-based DSSE program originally designed for outpatients. Implementation science principles were used to redesign D2Go for delivery by staff on medicine and surgery units in a tertiary care hospital to adults with type 2 diabetes (T2DM) using a tablet-based e-learning platform. Implementation efficacy was evaluated from staff and patient engagement perspectives. The Practical, Robust Implementation and Sustainability Model (PRISM) guided redesign. The team conducted qualitative evaluation (implementation barriers and facilitators); program redesign (via stakeholder feedback and education and human factors principles); implementation design for tablet delivery and patient engagement by unit staff; and a prospective implementation feasibility study. Among 596 T2DM patients identified on three medical/surgical units, 415 (69.6%) were program eligible. Of those eligible, 59 (14.2%) received, accessed, and engaged with the platform; and among those, 43 (72.9%) completed the intervention, representing just 10.4% of those eligible. Multilevel implementation barriers were encountered: staff (receptivity, time, production pressures, culture); process (electronic health record [EHR] integration, patient identification, data tracking, bedside delivery); and patient (receptivity, acuity, availability, accessibility). Most completers required technology support. Time constraints, limited EHR integration, and patient barriers markedly impeded implementation of the delivery of diabetes education at the bedside, despite stated staff interest. As a result, uptake and adoption of a tablet-based DSSE e-learning program in a high-acuity care setting was limited.


Treatment of bone and soft tissue sarcomas of the hand and wrist.
We studied 13 consecutive patients with bone and soft tissue sarcomas of the hand and wrist. Chondrosarcoma, Ewing's sarcoma, synovial sarcoma and epithelioid sarcoma were the most frequent histological diagnoses. Limb-sparing surgery was performed in ten patients but eventually three patients required an amputation. Surgical margins were wide in nine patients and marginal in four. Adjuvant therapy for nine patients consisted of chemotherapy in five and chemotherapy with radiation in four. Local recurrence occurred in two patients with epithelioid sarcoma. There was no significant relationship between surgical margin and local recurrence. Distant metastasis occurred in four patients. The 5-year survival rate was 66%. The mean functional score was 87%. Our study indicates that treatment consisting of resection of these tumours with either a wide margin or a marginal margin followed by adjuvant radiation appeared to be safe and resulted in an acceptable degree of limb function except in the patients with epithelioid sarcoma.


Studying the association between postgraduate trainees' work hours, stress and the use of maladaptive coping strategies.
The growing debate regarding long working hours of postgraduate trainees has been receiving considerable attention recently. This greater workload contributes to increasing stress. Our objective was to specifically study the association between long working hours, stress and the greater use of 'maladaptive' coping strategies. A cross-sectional descriptive study was carried out on all interns and residents at the Aga Khan University Hospital during February to May, 2005. Level of stress was measured by use of General Health Questionnaire (GHQ-12) and the use of maladaptive coping mechanisms through Brief Cope-28. 55.1% scored over the threshold for mild stress i.e. GHQ > 3, while more than 46% of the trainees scored over the threshold of more than 4 for morbid stress. Trainees under stress reported more working hours on average as compared to those not under stress, 83.8 and 74.7 hours respectively. At the same time, those working for longer hours were more likely to have used these negative coping mechanisms, which would further contribute to more stress rather than relieving it. Significant levels of stress have been identified. Along with this, those working for longer hours were more likely to have used these negative coping mechanisms. Reduction of working hours is important. Simultaneously, interventions need to be planned at imparting knowledge, awareness and skills to cope with various kinds of stressors encountered by a trainee during his/her training. Additionally, limits need to be devised for the working hours of the trainees.


Effect of silicone oil heat treatment on the chemical composition, cellulose crystalline structure and contact angle of Chinese parasol wood.
The effect of silicone oil heat treatment (SOTH) on the chemical composition, cellulose crystalline structure, thermal degradation and contact angle of Chinese parasol wood were examined in this study. Samples were heated at 150°C, 180°C and 210°C for 2h and 8h, after SOHT chemical composition, fourier transformed infrared (FTIR), thermogravimetric analysis (TGA) and X-ray diffraction (XRD) of the treated samples were evaluated. Results showed that the chemical components of the wood were affected after SOHT particularly when treated at 210°C for 8h. Changes in the chemical components was due to the degradation of biopolymer components of the wood during SOHT. The crystallinity index of cellulose and contact angle of the SOHT samples was increased. The findings demonstrate the potential of SOHT for modification of wood. Thus an economical and eco-friendly approach to thermally modified wood was achieved in this study.


[Impact of COVID-19-pandemic on Clinical Care, Work Flows and Staff at a University Hospital: Results of an Interview-study at the UKE].
The study investigates the impact of the COVID-19 pandemic on health services with and without specific health care of COVID-19 patients through the eyes of leading physicians at the University Medical Center Hamburg-Eppendorf (UKE). From April 30 to May 12, 2020, four interviewers conducted 38 expert interviews via telephone, video or face-to-face by using a semi-standardized questionnaire. The standardized answers were analysed descriptively. The free text-answers were subject to a qualitative content analysis. The categories were analysed via quantitative frequency distributions. All chief physicians with responsibility for inpatient and outpatient health care at the UKE took part in this study (N=38). The leading physicians reported numerous changes regarding occupancy in the hospital, patient composition, work flows and diagnostic as well as therapeutic measures. Additionally, various arrangements were necessary to cover the needs of prevention, treatment and follow-up care as well as protection of staff. Measures showed, on the one hand, a strong reduction in occupancy and workload in most inpatient and outpatient clinics. On the other hand, the amount of work also increased by fundamental transitions of work flows, communication, staff structure and hygiene measures. Many respondents commented positively on the rapid and efficient setup of a digital communication structure. Partially, staff was strained by the pandemic itself and by the associated measures. The results of the study help to understand and assess the effects of the pandemic on health care, work flows and staff. The findings may support the specification and adaptation of prospective measures and processes for pandemic crisis situations. Future studies should investigate how staff beneath the highest executive level experienced and evaluated this crisis and consequences.


Anterior vaginal wall tenderness (AVWT) as a physical symptom in chronic pelvic pain.
Chronic pelvic pain is often difficult to diagnose and treat properly. Physicians called on to treat this problem may not be able to give a specific diagnosis. The aim of this study was to see whether the physical presence of anterior vaginal wall tenderness could help narrow down and elucidate diagnoses in a practice focusing on diagnosis and treatment of chronic pelvic pain. The study cohort comprised 284 patients with chronic pelvic pain limited to gynecologic and lower urinary problems. Histories, physical examinations, and endoscopic procedures were performed on each patient. An analysis of this information was conducted. Of the chronic pelvic pain patients, 78% had endometriosis, 81% had interstitial cystitis, and 61% had both concurrently. The sensitivity of anterior vaginal wall tenderness (AVWT) in patients with interstitial cystitis was 95%, and in those with only endometriosis and no interstitial cystitis, the sensitivity was 17%. The positive predictive value for interstitial cystitis was 85%, and for endometriosis it was 67%. Examination of the anterior vaginal wall with an empty bladder at the initial examination can lead one to suspect interstitial cystitis and possibly either concomitant or singular endometriosis and allow the physician to approach the workup accordingly.


Intraocular pressure study using monitored forced-infusion system phacoemulsification technology.
To optimize phacoemulsification efficiency by varying the intraocular pressure (IOP) using the Centurion Vision System, a monitored forced-infusion system. John A. Moran Eye Center Laboratories, University of Utah, Salt Lake City, Utah, USA. Laboratory investigation. Porcine lenses were soaked in formalin and divided into 2.0 mm cubes; 0.9 mm balanced tips were used. Intraocular pressure levels were tested from 30 to 110 mm Hg at 10 mm Hg intervals. Vacuum was set at 500 mm Hg, aspiration at 35 mL/min, and torsional power at 60%. Efficiency (time to lens removal) and chatter (number of lens fragment repulsions from the tip) were measured. There was a linear relationship between efficiency and IOP. Increasing IOP led to an increase in efficiency (ie, to a decrease in time necessary to remove the lens fragment) (R(2) = .5769, P = .0176). Chatter correlated with IOP in the range of 30 to 50 mm Hg (R(2) = .4506, P = .0448) and was minimal at higher IOPs. Increasing IOP in the monitored forced-infusion system improved efficiency. Chatter was also decreased or eliminated with increasing IOP. Additional studies will be required to understand the reasons for these findings. None of the authors has a financial or proprietary interest in any material or method mentioned.


Effect of natural organic matter on aggregation behavior of C60 fullerene in water.
The stability of C(60) fullerene particles in water affects its mobility, bioavailability, and toxicity to organisms. Natural organic matters (NOMs) have pronounced effects on the aggregation behavior of C(60) fullerene. This study was to examine the effects of NOM structural properties on the aggregation behavior of fullerene water suspension (FWS). Fulvic acid (FA), tannic acid (TA), and two structurally different humic acids (HA1 and HA7) were studied. HA1 and HA7 were sequentially extracted HAs, where HA7 was more hydrophobic than HA1 and had a higher molecular weight. Aggregation was induced by addition of varying amounts of Ca(2+) to the FWS with 2 mg/L of each NOM. The absolute value of zeta potential |ζ| of pure FWS increased after addition of any type of NOM. Addition of Ca(2+) to the FWS+NOM system decreased |ζ| of fullerene almost uniformly for all types of NOM. FWS critical coagulation concentration (CCC) was equal to 14.5, 6.5, 5.4, and 3.7 mM Ca(2+) for HA7, HA1, FA, and TA, respectively. The order of increasing CCCs was positively correlated to the NOMs molecular weight and negatively to their polarity. A nearly constant ζ for FWS+NOM system at a wide range of Ca(2+) concentrations suggested the steric stability rather than electrostatic one. This study highlighted the role of NOM in the fate of manufactured nanoparticles in the environment and linked the structural properties of NOM to their interaction with manufactured nanoparticles.


Xanthogranulomas of choroid plexus.
Computed tomographic features of xanthogranulomas of the choroid plexus are presented. The characteristic location of bilateral intense homogeneously enhanced masses with central lucencies is thought to be diagnostic of xanthogranuloma of the choroid plexus.


Sex-dependent hippocampal volume reductions in schizophrenia relate to episodic memory deficits.
Morphological abnormalities of the hippocampus might form the neurobiological basis of memory dysfunction in schizophrenia. Hippocampal volume was found to be bilaterally reduced in male, but not in female, subjects with schizophrenia. Right hippocampal volume was significantly related to impaired visual learning.


Analysis of total and surface membrane lipids of Schistosoma mansoni.
Lipids extracted from whole worm homogenates and tegumental outer membranes of guinea pig-derived 5-day, 2-, 3- and 6-week old schistosomes have been analysed by thin layer chromatography. Six-week hamster-derived parasites have been studied for comparative purposes. All homogenates contained neutral lipids, cholesterol and several phospholipids; phosphatidyl choline and phosphatidyl ethanolamine were major components. Phospholipid (P3) was absent from homogenates of 5-day worms but was present in older parasites. A single phospholipid (P4) which co-chromatographed with phosphatidyl glycerol was unique to hamster-derived parasites. One glycolipid (G1) was ubiquitous to all homogenates and co-chromatographed with the monogalactosyl ceramide marker. A second sugar-containing lipid (G2) was unique to 3-week worm homogenates, and was highly polar. It was resolved beneath the trigalactosyl ceramide marker. Tegumental membranes isolated from 6-week adults contained at least five glycolipids, four of which were also highly polar. Cholesterol and two dominant phospholipids occurred in the membranes of 2-, 3-, and 6-week worms. One phospholipid co-chromatographed with phosphatidyl choline; the other had an Rf value (relative band speed) equivalent to phosphatidyl ethanolamine. Membranes from liver stage parasites contained a further phospholipid which cochromatographed with sphingomyelin, and three additional, phosphate-staining lipids (P1, P3 and P6). Five sugar-containing lipids occurred in adult membranes only; four were highly polar, being resolved near the origin. Similar components were identified in extracts of host erythrocytes. The remaining membrane lipid appeared homologous to G1 identified in the whole worm homogenates. Important changes in lipid composition thus occur during schistosome growth and maturation in guinea pigs; moreover, worms derived from different rodents express different lipids.


Asbestos and renal adenocarcinoma: a case-control study.
A case-control study of renal adenocarcinoma has corroborated the hypothesis that asbestos is a cause of the disease. The odds of having been moderately or heavily exposed to asbestos 30 years before diagnosis were 45:473 among cases, whereas the comparable odds among controls were 26:492. A matched-pair analysis yielded an exposure odds ratio of 1.8 with 95% confidence limits of 1.1 and 3.1. After controlling for potential confounders and selection factors by means of logistic regression, the incidence rate ratio was estimated to be 1.6, with a one-sided 95% confidence limit of 1.0.


Time to biochemical failure and prostate-specific antigen doubling time as surrogates for prostate cancer-specific mortality: evidence from the TROG 96.01 randomised controlled trial.
Surrogate endpoints for prostate cancer-specific mortality after curative primary treatment are not well established. We sought to assess time to biochemical failure (TTBF) and prostate-specific antigen doubling time (PSADT) after failure of curative treatment as candidates for this endpoint. PSA and survival data from the Trans-Tasman Radiation Oncology Group (TROG) 96.01 trial were used to assess surrogate candidates. Between June 28, 1996, and Feb 16, 2000, 802 eligible men with locally advanced prostate cancer were randomly allocated to prostatic irradiation alone, or to 3 or 6 months of maximum short-term androgen deprivation (STAD) before and during radiation. Successful surrogates were required to satisfy the Prentice criteria and to predict the trial finding. The TROG 96.01 trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12607000237482. 6 months of STAD was shown to significantly decrease prostate cancer-specific mortality compared with radiation alone, but 3 months of STAD did not result in a decrease. Relative to radiation alone, the hazard ratio of prostate cancer-specific mortality from randomisation was 0.95 (95% CI 0.63-1.41; p=0.79) in the 3-month STAD treatment arm and 0.56 (0.36-0.88; p=0.01) in the 6-month arm. PSADT predicted the trial finding and satisfied all four Prentice criteria at the cutpoints of less than 12 months and less than 15 months, with proportion of treatment effect ratios between 0.36 and 0.56. Time to biochemical failure was better than PSADT at predicting the trial finding and satisfying all four Prentice criteria at cutpoints of less than 1.5, less than 2, and less than 2.5 years, with proportion of treatment effect ratios between 0.45 and 0.64. This study provides proof of principle that TTBF and PSADT can be useful as surrogate endpoints for prostate cancer-specific mortality and offer potential to substantially reduce follow up in clinical trials. These endpoints now require assessment in multi-trial meta-analyses before use in clinical trials.


[Clinical bioethics for primary health care].
The clinical decision making process with ethical implications in the area of primary healthcare differs from other healthcare areas. From the ethical perspective it is important to include these issues in the decision making model. This dissertation explains the need for a process of bioethical deliberation for Primary Healthcare, as well as proposing a method for doing so. The decision process method, adapted to this healthcare area, is flexible and requires a more participative Healthcare System. This proposal involves professionals and the patient population equally, is intended to facilitate the acquisition of responsibility for personal and community health.


Typing of human herpesvirus-6 DNA by restriction endonuclease cleavage of the polymerase chain reaction product.
A 591 bp portion of the HindIII H (pZVH14) fragment of human herpesvirus-6 (HHV-6) strains GS (type A) and R-147 (type B) DNA was amplified by the polymerase chain reaction (PCR) using specific primers. While AluI cleaved the amplified DNA of both types of HHV-6, EcoRV cut the type A but not the type B DNA; vice versa, HaeIII cleaved the type B but not the type A DNA.


Dexamethasone-mediated induction of mouse mammary tumor virus RNA: a system for studying glucocorticoid action.
We have investigated the mechanisms by which dexamethasone (a synthetic glucocorticoid) stimulates the production of mouse mammary tumor virus (MMTV) by cell cultures derived from mammary carcinomas of GR mice. Treatment of these cells with dexamethasone stimulates a rapid accumulation of intracellular virus-specific RNA which is dependent upon RNA synthesis but not upon DNA or protein synthesis. The effect of dexamethasone is probably mediated by a specific and saturable glucocorticoid receptor. We conclude that the accumulation of MMTV RNA is a primary response to dexamethasone and that the rate of synthesis of MMTV RNA is probably accelerated by treatment with dexamethasone.


Highly sensitive peptide-based probes for protein tyrosine phosphatase activity utilizing a fluorogenic mimic of phosphotyrosine.
Fluorescent probes that can be incorporated into peptides and proteins are in high demand, with applications ranging from cellular imaging to binding and activity assays. Here, we report the high yielding synthesis of an enantiomerically pure phosphocoumarin-based amino acid and its incorporation into peptides via standard solid-phase peptide synthesis methodologies. Peptides containing this new amino acid serve as highly sensitive fluorogenic probes for protein tyrosine phosphatase activity.


A comparison of performance between a deep learning model with residents for localization and classification of intracranial hemorrhage.
Intracranial hemorrhage (ICH) from traumatic brain injury (TBI) requires prompt radiological investigation and recognition by physicians. Computed tomography (CT) scanning is the investigation of choice for TBI and has become increasingly utilized under the shortage of trained radiology personnel. It is anticipated that deep learning models will be a promising solution for the generation of timely and accurate radiology reports. Our study examines the diagnostic performance of a deep learning model and compares the performance of that with detection, localization and classification of traumatic ICHs involving radiology, emergency medicine, and neurosurgery residents. Our results demonstrate that the high level of accuracy achieved by the deep learning model, (0.89), outperforms the residents with regard to sensitivity (0.82) but still lacks behind in specificity (0.90). Overall, our study suggests that the deep learning model may serve as a potential screening tool aiding the interpretation of head CT scans among traumatic brain injury patients.


Optimization of a Rabbit Dry Eye Model Induced by Topical Instillation of Benzalkonium Chloride.
To optimize a rabbit dry eye model induced by topical instillation of benzalkonium chloride (BAC), reduce the days of instillation of the original model by increasing the concentration of BAC from 0.1% to 0.2%. An experimental, prospective, and randomized study was performed on 10 male New Zealand white rabbits, divided into two groups, considering both eyes: 5 rabbits as control (n = 10) and 5 rabbits with 0.2% BAC treatment (n = 10). Saline solution (control) and 0.2% BAC were instilled for 5 consecutive days, twice daily. Tear secretion with and without anesthesia, tear breakup time, tear osmolarity, corneal staining, conjunctival hyperemia, density of goblet cells, height of mucin cloud, and transcript levels of IL-6 were measured before and after the treatment. After the instillation of 0.2% BAC for 5 consecutive days, there was a significant increase in tear secretion without anesthesia (P < 0.001), corneal staining (P < 0.001), conjunctival hyperemia (P < 0.001), and levels of IL-6 mRNA (P=0.005) compared to the control group. Conversely, there was a decrease in tear secretion with anesthesia (P < 0.001), tear breakup time (P=0.007), tear osmolarity (P < 0.001), density of goblet cells (P < 0.001), and height of mucin cloud (P < 0.001). The topical instillation of 0.2% BAC for 5 consecutive days, twice daily, was a proper procedure to induce a rabbit dry eye model, reducing the number of days of instillation compared to the original model (14 days).


The interferon-like proteins, Vagos, in Fenneropenaeus merguiensis elicit antimicrobial responses against WSSV and VPAHPND infection.
The Vago interferon-like protein participates in the interplay between interferon regulatory factors and the expression of immune-responsive genes. Vago was initially perceived to participate only in the antiviral activation through JAK/STAT pathway. However, certain isoforms of Vago can stimulate antimicrobial responses. Here we identify Vago isoforms in Fenneropenaeus merguiensis (FmVagos) and how they function in antiviral and antibacterial responses against highly invasive pathogens, including white spot syndrome virus (WSSV) and Vibrio parahaemolyticus (VPAHPND). Three isoforms of FmVagos were identified: FmVago4, FmVago5a, and FmVago5b, and expressed throughout tissues of the shrimp. During infection, FmVago4, FmVago5a, and FmVago5b, were up-regulated after WSSV and VPAHPND challenges at certain time points. Pre-injection of purified recombinant FmVago4 (rVago4), FmVago5a (rVago5a), and FmVago5b (rVago5b) proteins could significantly reduce the mortality of shrimp upon WSSV infection, while the increase of survival rate of VPAHPND-infected shrimp was observed only in rVago4 treatment. The immunity routes that FmVagos might instigate in response to the pathogens were examined by qRT-PCR, revealing that the JAK/STAT pathway was activated after introducing rVago4, rVago5a, and rVago5b, while the Toll/IMD pathway and proPO system, combined with PO activity, were provoked only in the rVago4-treated shrimp. Our finding suggests cross-talk between Vago's antiviral and antimicrobial responses in shrimp immunity. These findings complement previous studies in which Vago and its specific isoform could promote viral and bacterial clearance in shrimp.


Multilayer stabilization for fabricating high-loading single-atom catalysts.
Metal single-atom catalysts (M-SACs) have emerged as an attractive concept for promoting heterogeneous reactions, but the synthesis of high-loading M-SACs remains a challenge. Here, we report a multilayer stabilization strategy for constructing M-SACs in nitrogen-, sulfur- and fluorine-co-doped graphitized carbons (M = Fe, Co, Ru, Ir and Pt). Metal precursors are embedded into perfluorotetradecanoic acid multilayers and are further coated with polypyrrole prior to pyrolysis. Aggregation of the metals is thus efficiently inhibited to achieve M-SACs with a high metal loading (~16 wt%). Fe-SAC serves as an efficient oxygen reduction catalyst with half-wave potentials of 0.91 and 0.82 V (versus reversible hydrogen electrode) in alkaline and acid solutions, respectively. Moreover, as an air electrode in zinc-air batteries, Fe-SAC demonstrates a large peak power density of 247.7 mW cm-2 and superior long-term stability. Our versatile method paves an effective way to develop high-loading M-SACs for various applications.


Inhibition of VEGFR2 and EGFR signaling cooperatively suppresses the proliferation of oral squamous cell carcinoma.
Epidermal growth factor receptor (EGFR) is frequently overexpressed in oral squamous cell carcinoma (OSCC), and EGFR-targeting therapeutics have been widely employed to treat patients with a variety of carcinomas including OSCC. Here, we aimed to investigate alternative signaling for OSCC survival under the disruption of EGFR signaling. OSCC cell lines, namely HSC-3 and SAS, were utilized to investigate how EGFR disruption affects cell proliferation. Gene set enrichment analysis was performed to examine how EGFR disruption affects oncogenic signaling in OSCC cells. Disruption of KDR gene was performed using CRISPR/Cas9 techniques. A VEGFR inhibitor, vatalanib was used to research the impact of VEGFR inhibition on OSCC survival. EGFR disruption significantly decreased the proliferation and oncogenic signaling including Myc and PI3K-Akt, in OSCC cells. Chemical library screening assays revealed that VEGFR inhibitors continued to inhibit the proliferation of EGFR-deficient OSCC cells. In addition, CRISPR-mediated disruption of KDR/VEGFR2 retarded OSCC cell proliferation. Furthermore, combined erlotinib-vatalanib treatment exhibited a more potent anti-proliferative effect on OSCC cells, compared to either monotherapy. The combined therapy effectively suppressed the phosphorylation levels of Akt but not p44/42. VEGFR-mediated signaling would be an alternative signaling pathway for the survival of OSCC cells under the disruption of EGFR signaling. These results highlight the clinical application of VEGFR inhibitors in the development of multi-molecular-targeted therapeutics against OSCC.


Electrocardiographic low-frequency QRS notching and ventilatory impairment in patients with pulmonary tuberculosis.
The occurrence of notching in the initial and terminal parts of the QRS complex of the ECG was studied in a series of 1072 patients with active or healed pulmonary tuberculosis. Terminal notchings were associated with ventilatory impairment: in the male group the percentage of patients with terminal notching increased from 5 to 20% as the FEV1.0% decreased from larger than or equal to 80 to below 40. Initial notchings were not associated with ventilatory impairment. The relationships were similar when studied separately in groups with and without left heart disease.


Case Study: Landscape of Chimeric RNAs in Bladder Cancer.
Chimeric RNAs and their products have been shown to be closely associated with tumorigenicity and development in a variety of tumors, making them attractive diagnostic markers and therapeutic targets. In previous chapters, we introduced related research techniques and methods for studying chimeric RNAs. Here, we present an overview of the landscape of chimeric RNAs in bladder cancer and verification of two fusion transcripts which are associated with bladder cancer. We used bioinformatics to analyze the TCGA bladder urothelial carcinoma RNA-sequencing dataset, which contains 414 bladder cancer samples and 19 matched normal samples. We identified 19,547 chimeric RNAs and applied multiple criteria to avoid false positives, reducing this list to 271 high-confidence chimeric RNAs, 13 of which specifically expressed in cancer. We validated 6 of these chimeric in clinical bladder cancer samples, including CHFR-GOLGA3, which was found to be expressed significantly higher in bladder cancer samples in comparison to matched normal samples. We have determined that this chimeric RNA is produced by cis-splicing between adjacent genes (cis-SAGe). Further, we found that CHFR-GOLGA3 is mainly expressed in the nucleus, suggesting that it may not encode chimeric protein and instead act as noncoding RNA. Our findings establish the chimeric landscape of bladder cancer and provide a research strategy for how to conduct chimeric RNA research in other tumors.


Altered resting functional network topology assessed using graph theory in youth with attention-deficit/hyperactivity disorder.
Notwithstanding an extensive literature about attention-deficit/hyperactivity disorder (ADHD) and brain structure and function, the controversy of ADHD resulting from dysfunction or developmental delay remains unclear. Graph analysis studies have reached consensus about the pattern of increased integration and decreased randomness during childhood and early adulthood. Here, we hypothesized that ADHD is a neurodevelopmental disorder resulting from developmental delay and would show a pattern of decreased integration and increased randomness during childhood and early adulthood compared with typically developing children. To test this hypothesis, publicly available resting-state fMRI data from 102 children with ADHD and 143 typically developing controls (TDC) were compared using graph theoretical analysis. Functional connectivity was estimated using Pearson correlation analysis, and network topology was characterized using small-world (SW) and minimum spanning tree (MST) properties. The mean strength of global connectivity was significantly weaker in those with ADHD and was related to ADHD diagnosis scores. Significant group differences were observed for SW(clustering coefficient, path length, global and local efficiency) and MST (leaf number, kappa and hierarchy) topology. In addition, except for global efficiency, all of these parameters showed significant correlations with ADHD-related disability. The topology of SW and MST showed less integration and more randomness, which confirmed that ADHD is a disorder associated with developmental delay. Moreover, the topology of resting-state functional networks in children with ADHD that show abnormalities was associated with the degree of disability, which can be considered neurological hallmarks of neurodevelopmental disorders and may facilitate the evaluation and monitoring of clinical status in individuals with ADHD.


Congenital disconnection of the pulmonary arteries.
Disconnected pulmonary artery (PA) is a rare anomaly that can be isolated or associated with complex intracardiac malformations. Early reimplantation of the disconnected PA is recommended to allow growth and satisfactory pulmonary perfusion while preventing collateral artery development. The aim of this study was to describe the characteristics of patients with disconnected PA and, for those who had surgical reimplantation, to determine the incidence, delay and predictive factors of reintervention for reconnected PA stenosis. We include patients with the diagnosis of congenitally disconnected PA and surgical repair at our institution. Retrospective observational study of 55 patients with a disconnected PA. Fifty-one underwent surgical correction and were followed up at our institution between 2000 and 2022. Disconnected PAs were observed in isolation in 31% of the cases. The most frequent form was left PA originating from the arterial duct (58%). The reimplantation was done at the median age of 12 days. Anastomotic stenosis was observed during follow-up in 71% of the patients with 75% of them requiring reintervention (55% of the population). The median delay to reintervention was 3.2 years after reimplantation, and >25% of reinterventions on the reimplanted PA occurred within the first postoperative year. We found more reintervention if associated cardiac defect, without significant statistic difference. Weight at re-confluence, presence of ductal tissue at the origin of the PA and prior shunt placement on the disconnected PA were not found to be risk factors for reintervention. After surgical reimplantation of PA, >50% of patients required reintervention for PA stenosis. Technical improvements should be sought to reduce the incidence of this complication.


Age-related changes in the motor response to environmental novelty in the rat.
To examine age-related changes in responsiveness to environmental novelty, 3-, 12-, and 24-month-old male Fischer 344 rats were maintained on a restricted diet and exposed to a modified open field for 10 min on each of 10 consecutive days. On the first day of testing, animals of all groups showed equal amounts of rearing. While the 3-month animals continued to show approximately the same levels of rearing until the 8th day, by day 5, the older groups (12- and 24-month) had significantly reduced their rearing. Conversely, grooming was initially highest among the 24-month-old animals. While 3- and 12-month rats showed habituation of grooming, the oldest animals failed to habituate their grooming response by day 5. By day 10, there were no significant differences among the groups in either rearing or grooming. Although food was available in the center of the modified open field, there was little eating and there were no differences among groups. However, all animals did eat quickly when food was made available in their home cages. Thus, all animals displayed a profile of stress-related responses to open field exposure. Plasma corticosterone levels likewise were elevated in the modified open field. Some, but not all, components of this response profile habituated over the 10 days of exposure. Three-month-old animals responded to the novelty predominantly by rearing and 24-month animals predominantly by grooming. This suggests that with aging, locomotor responses to stress are replaced by a more self-directed form of displacement activity.


[Effects of bromantane and sidnocarb on long-term operant conditioning and its vegetative correlates in rats].
Bromantan (20 mg/kg, p.o.) and sydnocarb (10 mg/kg, p.o.) augment the efficacy of a 5-h operant activity in rats, the effect being achieved through different pathways. Sydnocarb increases the number of operant reactions and exhausts the sympathico adrenal system reserves. Bromantan favors the activity optimization by reducing the number of errors at a smaller number of operant reactions. Bromantan increases the tension of motivational component (electric pain irritation avoidance), whereas sydnocarb decreases this component of the operant behavior. None of the two drugs affects the degree of functional activation of the cardiovascular system.


Properties of aspirin modified enteric polymer prepared by hot-melt mixing.
Melt mixing in batch equipment or continuous extruders is a technique that recently gained the attention of the pharmaceutical industry. The present work has employed hot-melt mixing to prepare a modified enteric matrix, as a delayed-release dosage form. Different concentrations of aspirin (ASP) ranging from 10 to -30% (w/w) were melt-mixed with a plasticized methacrylic acid copolymer, Eudragit(®) L100-55 in a batch mixer for 5 min at 100 °C which is above the plasticized polymer's glass transition temperature and below the ASP's melting point. The samples were cooled down to room temperature and compressed to thin discs. Processing ASP with Eudragit(®) L100-55 did not promote hydrolysis of ASP. X-ray diffraction spectra obtained at room temperature revealed that aspirin was present in a crystalline state. However, at elevated temperatures the dissolved aspirin displayed a plasticizing effect by reducing the glass transition temperature (Tg) and lowering the viscosity of the polymer in proportion to its increasing concentration. The addition of ASP altered to some extent the rheological behavior of the polymer from rubbery to viscous. However, the amount of ASP loading had no significant impact on the dissolution profiles. The samples met USP delayed-release requirements and the API release mechanism was shown to be diffusion dominant.


Will 37Ar emissions from light water power reactors become an obstacle to its use for nuclear explosion monitoring?
37Ar is a promising candidate for complementing radioxenon isotopes as indicators of underground nuclear explosions. This study evaluates its potential anthropogenic background caused by emissions from commercial pressurized water reactors. Various 37Ar production pathways, which result from activation of 36Ar and of 40Ca, respectively, are identified and their emissions quantified. In-core processes include (1) the restart of operation and degassing of the primary cooling water after maintenance and refueling shutdown, (2) the replacement of primary coolant water for limiting its tritium concentrations, and (3) the leakage of 37Ar produced from calcium impurities in UO2 after fuel rod failures. Activation of air and of calcium in concrete within the biological shield are major out-of-core production pathways. Whereas emissions from in-core processes are transient, a rather constant 37Ar source term results from its out-of-core production. Generic atmospheric dispersion simulations indicate that already at moderate distances from the emitter, concentrations of 37Ar caused by routine reactor operations are far below its cosmogenic background in air. The only exception results from an inadvertent reactor re-start without operation of the primary cooling water degassing system for prolonged time. Such an event also causes high emissions of 41Ar which can be used for discriminating its 37Ar signal from an underground nuclear explosion.


[Content and form characteristics that predict discriminating power in personality items: an item response theory-based analysis].
In two personality item pools that measure extraversion and neuroticism, the relations between three groups of itemmetric properties and the estimated discrimination indexes according to the two-parameter model are assessed. The itemmetric properties, which are conceptualized as dimensions, are: verbal complexity, ambiguity, and trait indicativity, and the hypotheses concerning their impact on the discriminating power are derived from a processing-stage model. The dimension of trait indicativity shows the clearest relations with the discriminating power in the expected direction. The implications of the results in the construction of personality measures are discussed.


Improved quality of life in Norwegian heart failure patients after follow-up in outpatient heart failure clinics: results from the Norwegian Heart Failure Registry.
To evaluate the quality of life in heart failure (HF) outpatients attending multidisciplinary disease management programmes at HF clinics in Norwegian hospitals. Data from HF patients at 24 hospital outpatient clinics were entered in a common database; The Norwegian Heart Failure Registry. Quality of life assessment was done using Minnesota Living with Heart Failure Questionnaire (MLHF). The quality of life assessment was optional at each hospital and was done both at initial evaluation and after 6 months of stable follow-up. A total of 3632 patients were included in the registry and 1778 patients had at least one assessment of quality of life. The mean MLHF score improved significantly from 2.1 at the initial evaluation to 1.4 six months after leaving the clinic (P < 0.001). There was a significant difference in MLHF score between hospitals and baseline MLHF score was significantly associated with NYHA functional class, hospitalizations 6 months before entering the registry, and brain natriuretic peptide; and inversely related to age and systolic blood pressure. Minnesota Living with Heart Failure score was an independent predictor of mortality in this population. Quality of life assessed with MLHF improved after follow-up at outpatient HF clinics. Minnesota Living with Heart Failure score was significantly related to functional status, laboratory and demographic variables, and was an important predictor of prognosis.


Comparative susceptibility of three Western honeybee taxa to the microsporidian parasite Nosema ceranae.
Genetic diversity of a host species is a key factor to counter infection by parasites. Since two separation events and the beginning of beekeeping, the Western honeybee, Apis mellifera, has diverged in many phylogenetically-related taxa that share common traits but also show specific physiological, behavioural and morphological traits. In this study, we tested the hypothesis that A. mellifera taxa living in a same habitat should respond differently to parasites like Nosema ceranae, a microsporidia living in host's midgut. We used the Poulin and Combes' concept of virulence to compare the susceptibility of three A. mellifera taxa to N. ceranae infection. Three criteria were measured 10 days post-infection (dpi): the host mortality, the host sugar consumption and the development success of the parasite (i.e. number of spores produced). Interestingly, we showed that the observed variation in susceptibility to infection by N. ceranae is not linked to honeybee taxa but results from the variability between colonies, and that those differences are probably linked to genetic variations. The use of these three criteria allows us to conclude that the differences in susceptibility are mediated by a genetic variability in honeybee workers from resistance to tolerance. Finally, we discuss the consequences of our findings for beekeeping management.


The polygenetically inherited metabolic syndrome of WOKW rats is associated with insulin resistance and altered gene expression in adipose tissue.
Wistar Ottawa Karlsburg W (RT1u) rats (WOKW) develop a complete metabolic syndrome closely resembling the human disease. The aim of this study was to characterize the phenotype of adipose tissue in WOKW rats with regard to adipocyte metabolism, insulin resistance, and gene expression and thus to define the phenotype more precisely. Glucose metabolism, insulin sensitivity, and gene expression of key adipocyte genes, including adiponectin, interleukin 6 (Il6), 11 beta-hydroxysteroid dehydrogenase (11beta Hsd), peroxisome proliferator-activated receptor gamma (Ppar gamma), forkhead box O1 (Foxo1), glucose transporter 4 (Glut4), CCAAT/enhancer binding protein (C/ebp alpha), and fatty acid synthase (Fasn) were characterized in adipocytes from epididymal and subcutaneous fat depots of 28-week-old male WOKW rats and Dark Agouti (DA) controls. WOKW rats display decreased insulin-stimulated glucose uptake and decreased insulin sensitivity during lipogenesis and lipolysis in isolated adipocytes. The severe insulin resistance predominantly in epididymal adipose tissue of WOKW rats is associated with a 10-fold decrease in adipocyte adiponectin gene expression, decreased Ppar gamma, but increased Foxo1 gene expression compared to DA rats. Insulin resistance in adipose tissue is associated with altered adipocyte gene expression in WOKW rats, additionally completing the picture of the metabolic syndrome in this animal model. This fact not only qualifies the WOKW rat for further detailed analysis of genetic determinants of metabolic syndrome but also highlights its suitability for pharmacological research.


Volatile components of peel and leaf oils of lemon and lime species.
Peel and leaf oils of 43 taxa of lemons and limes were obtained from fruits and leaves collected from trees submitted to the same pedoclimatic and cultural conditions. Their chemical composition was investigated by capillary GC, GC-MS, and (13)C NMR, and the results were submitted to principal component analysis to check for chemical variability. Three major chemotypes were distinguished for lemon peel oils: limonene; limonene/beta-pinene/gamma-terpinene; and limonene/linalyl acetate/linalool. Two chemotypes were identified for lemon leaf oils: limonene/beta-pinene/geranial/neral and linalool/linalyl acetate/alpha-terpineol. In lime peel oils, four chemotypes were distinguished: limonene; limonene/gamma-terpinene; limonene/beta-pinene/gamma-terpinene; and limonene/gamma-terpinene/beta-pinene/oxygenated products. Four others were identified for lime leaf oils: beta-pinene/limonene; limonene/geranial/neral; limonene/linalool/citronellal; and limonene/sabinene/citronellal/linalool. These results were interpreted using principal component analysis.


Diagnosis and Surgical Management of Uroenteric Fistula.
Uroenteric fistulae can occur between any part of the urinary tract and the small and large bowel. Classification is generally based on the organ of origin in the urinary tract and the termination of the fistula in the segment of the gastrointestinal tract. Surgery is often necessary. Congenital fistulae are rare, with most being acquired. Uroenteric fistulae most frequently occur in a setting of inflammatory bowel disease. Imaging often helps in the diagnosis. Management of urinary fistulae includes adequate nutrition, diversion of the urinary tract, diversion of the gastrointestinal tract, treatment of underling inflammatory process or malignancy, and surgery.


High performance liquid chromatography determination of dexamethasone in plasma to evaluate its systemic absorption following intra-space pterygomandibular injection of twin-mix (mixture of 2 % lignocaine with 1:200,000 epinephrine and 4 mg dexamethasone): randomized control trial.
To determine systemic absorption of dexamethasone by detection of plasma concentration using high performance liquid chromatography following its administration along with local anesthetic agent as a mixture via pterygomandibular space. A prospective randomized double-blind clinical study was undertaken to analyze the plasma concentration of dexamethasone after intra-space pterygomandibular injection along with local anesthesia. The study was performed as per split mouth model where the mandibular quadrant allocation was done on a random basis considering each of the 30 patients is included in the two study interventions (SS and CS). For the study site (SS) procedures, dexamethasone was administered as a mixture (2 % lignocaine with 1:200,000 epinephrine and 4 mg dexamethasone) intra-space. In the control site (CS) procedures, a regular standard inferior alveolar nerve block was administered, and dexamethasone was given as intramuscular injection. The plasma dexamethasone determination was done in venous blood 30- and 60-min post injection using high performance liquid chromatography (HPLC). The clinical parameters like pain; swelling; and mouth opening on the first, third, and seventh post-operative day were analyzed and compared. No significant difference was found in the clinical parameters assessed; comparative evaluation showed less swelling in the SS interventions. The plasma concentration of dexamethasone for the CS interventions was 226 ± 47 ng/ml at 30-min and 316 ± 81.6 ng/ml at 60-min post injection, and for SS, it was 221 ± 81.6 ng/ml at 30-min and 340 ± 105 ng/ml at 60-min post injection. On inter-site (CS and SS) comparison, no statistically significant difference was ascertained in dexamethasone plasma concentration at 30-min post injection (P = 0.77) and at 60-min post injection. (P = 0.32). Intra-space (pterygomandibular space) administration of dexamethasone can achieve statistically similar plasma concentration of the drug as when the same dose is administered intramuscularly with demonstration of similar clinical effects.


N-Hydroxyphthalimide exhibits antitumor activity by suppressing mTOR signaling pathway in BT-20 and LoVo cells.
N-Hydroxyphthalimide (NHPI), an important chemical raw material, was found to have potent and selective anti-proliferative effect on human breast carcinoma BT-20 cells, human colon adenocarcinoma LoVo and HT-29 cells during our screening for anticancer compounds. The purpose of this study is to assess the antitumor efficacy of NHPI in vitro and in vivo and to explore the underlying antitumor mechanism. Cell cytotoxicity of NHPI was evaluated using MTS assay and cell morphological analysis. After NHPI treatment, cell cycle, apoptosis and mitochondrial membrane potential were analyzed using flow cytometer. The subcellular localization of eukaryotic initiation factor 4E (eIF4E) was analyzed by immunofluorescence assay. The antitumor efficacy of NHPI in vivo was tested in BT-20 xenografts. The underlying antitumor mechanisms of NHPI in vitro and in vivo were investigated with western blot analysis in NHPI-treated cancer cells and tumor tissues. Statistical significance was determined using Student's t-test. In vitro, NHPI selectively inhibited the proliferation and induced G2/M phase arrest in BT-20 and LoVo cells, which was attributed to the inhibition of cyclin B1 and cdc2 expressions. Furthermore, NHPI induced apoptosis via mitochondrial pathway. Of note, NHPI effectively inhibited mammalian target of rapamycin (mTOR) complex 1 (mTORC1) and mTOR complex 2 (mTORC2) signaling, and overcame the feedback activation of Akt and extracellular signal-regulated kinase (ERK) caused by mTORC1 inhibition in BT-20 and LoVo cells. In vivo, NHPI inhibited tumor growth and suppressed mTORC1 and mTORC2 signaling in BT-20 xenografts with no obvious toxicity. We found for the first time that NHPI displayed antitumor activity which is associated with the inhibition of mTOR signaling pathway. Our findings suggest that NHPI may be developed as a promising candidate for cancer therapeutics by targeting mTOR signaling pathway and as such warrants further exploration.


Hepatitis B core protein promotes liver cancer metastasis through miR-382-5p/DLC-1 axis.
The hepatitis B virus core protein (HBc), also named core antigen, is well-known for its key role in viral capsid formation and virus replication. Recently, studies showed that HBc has the potential to control cell biology activity by regulating host gene expression. Here, we utilized miRNA microarray to identify 24 upregulated miRNAs and 21 downregulated miRNAs in HBc-expressed HCC cells, which were involved in multiple biological processes, including cell motility. Consistently, the in vitro transwell assay and the in vivo tail-vein injection model showed HBc promotion on HCC metastasis. Further, the miRNA-target gene network analysis displayed that the deleted in liver cancer (DLC-1) gene, an important negative regulator for cell motility, was potentially targeted by several differentially expressed miRNAs in HBc-introduced cells. Introduction of miRNAs mimics or inhibitors and 3'UTR luciferase activity assay proved that miR-382-5p efficiently suppressed DLC-1 expression and its 3'-UTR luciferase reporter activity. Importantly, cotransfection of miR-382-5p mimics/inhibitors and the DLC-1 expression vector almost abrogated HBc promotion on cell motility, indicating that the miR-382-5p/DLC-1 axis is important for mediating HBc-enhanced HCC motility. Clinical HCC samples also showed a negative correlation between miR-382-5p and DLC-1 expression level. Furthermore, HBc-positive HCC tissues showed high miR-382-5p level and reduced DLC-1 expression. In conclusion, our findings revealed that HBc promoted HCC motility by regulating the miR-382-5p/DLC-1 axis, which might provide a novel target for clinical diagnosis and treatment.


Impaired pancreatico-biliary response to vagal stimulation and to cholecystokinin in human obesity.
We previously found that massively obese patients respond with less gastric acid secretion in response to vagal stimulation. This is compatible with the described association between experimental obesity and altered vagal function in the rat. To confirm this observation, the pancreatic and biliary responses to vagal stimulation were examined in nine nondiabetic obese patients against a background secretin infusion of 15 CU x h-1, and monitored after a subsequent injection of 75 IDU of cholecystokinin. Two separate marker perfusion systems were used in the stomach and duodenum, respectively, and blood samples were drawn for hormone analyses. In contrast to controls having normal body weight, the obese patients failed to respond with increments of pancreatic enzyme secretion and duodenal bile acids after stimulation with modified sham feeding. Cholecystokinin stimulated the pancreatic secretion of trypsin, amylase, and lipase, the emptying of bile acids, and the release of gastrin, but the patients' responses were only half that of the controls. In the resting state the obese had higher outputs of bile and pancreatic enzymes and higher plasma levels of pancreatic polypeptide compared with controls, but the pancreatic bicarbonate secretion rate was not different. The almost complete suppression of the basal gastric acid secretion by a low dose of intravenous (IV) secretin in controls did not occur in the obese. We conclude that massive obesity is associated with a reduced pancreatic and biliary response to vagal stimulation. Compared with controls, the digestive functions of the obese patients seem to be less sensitive to stimulation by exogenous cholecystokinin.(ABSTRACT TRUNCATED AT 250 WORDS)