The effects of smoking in pregnancy: a review of approaches to behavioural change.
A substantial body of evidence has now been accumulated which suggests that cigarette smoking during pregnancy can result in an increased incidence in the number of babies born of lower birth weight. There is also an increase in perinatal mortality in babies born to smoking mothers, as well as a higher incidence of spontaneous abortion, greater mortality and morbidity during the first year of life and a lower rate of growth and reduction in mental aptitude into late adolescence. Despite this compelling evidence it has been found that only a relatively small proportion of women who smoke actually stop when they become pregnant. It has been found that knowledge of the potential effects of smoking does not appear to exert a major influence on pregnant women's smoking behaviour. There is also relatively little research which addresses the reasons why some pregnant women continue to smoke during pregnancy. The issue is clearly complex and the evidence that does exist points to the need for health professionals to adopt more sophisticated interventions with pregnant women, which move beyond a simple educational approach.


[Leprosy-related disabilities after release from multidrug treatment: prevalence and spatial distribution].
To estimate the frequency of people with leprosy-related physical disabilities after release from multidrug treatment and to analyze their spatial distribution. Descriptive cross-sectional study with 232 leprosy patients treated between 1998 and 2006. Physical disabilities were assessed using the World Health Organization disability grading and the eye-hand-foot (EHF) sum score. The residential address of patients and rehabilitation centers were geocoded. It was estimated the overall frequency of physical disability and frequency by disability grade (grade 0, grade 1, and grade 2) according to the WHO disability grading taking into consideration clinical and sociodemographic variables in the descriptive analysis. Student's t-test, chi-square test (χ2), and Fisher's test were used as appropriate at a 5% significance level. Of the patients studied, 51.6% were female, mean age 54 years old (SD 15.7), 30.5% had less than 2 years of formal education, 43.5% were employed, and 26.9% were retired. Borderline leprosy was the most prevalent form of leprosy (39.9%). A total of 32% of these patients had disabilities according to the WHO disability grading and the EHF score. Disabilities increased with age (p = 0.029), they were more common in patients with multibacillary leprosy (p = 0.005) and poor self-rated physical health (p < 0.001). Those who required prevention/rehabilitation care traveled on average 5.5 km to the rehabilitation center. People with physical disabilities lived scattered across the city but they were mostly concentrated in the most densely populated and socioeconomically deprived area. There is a high frequency of people with leprosy-related disabilities after release from multidrug therapy. Prevention and rehabilitation actions should target uneducated and older patients, those who had multibacillary forms of leprosy and poor self-rated physical health. The travel distance to rehabilitation centers calls for reorganization of local care networks.


The role of radiotherapy in the management of malignant hemangiopericytoma: report of eleven new cases and review of the literature.
The response of hemangiopericytoma to radiation therapy was studied in 11 patients treated at Memorial Hospital. Response of greater or lesser degree was noted in 26 of 29 radiation therapy courses administered. These included 14 instances of complete tumor regression. Dose and tumor size were the main factors influencing response. The tumors tend to regress slowly and incompletely; yet effective relief of symptoms and long term local control (average duration 27 months) usually was achieved. These results and those reported by others believe the alleged inefficacy of radiation therapy in the management of these tumors. Palliative radiation therapy seems to be worthwhile even in advanced cases. Because of the high rate of local recurrence after surgical excision, treatment strategies combining local excision of large primary tumors with wide-field, high-dose radiation therapy are worthy of trial.


[Safety of early cardiac magnetic resonance imaging in acute myocardial infarction patients with stents].
In general, magnetic resonance imaging is contraindicated when the patient has a ferromagnetic prosthesis or implant. With coronary stents, there is a theoretical concern that use of magnetic resonance imaging shortly after implantation will dislodge the stent, thereby increasing the risk of thrombosis. However, the risk may be overestimated because modern coronary stents are not ferromagnetic or are only weakly so. The objective of this study was to determine whether carrying out cardiac magnetic resonance imaging shortly after stent implantation is a safe procedure in acute myocardial infarction patients. We carried out a retrospective study of 407 patients with ST-elevation acute myocardial infarction who were treated by stent implantation. Cardiac magnetic resonance imaging was performed in the first 14 (11) days after stent implantation in 86 of these 407 patients (group 1); it was not performed in the 321 patients in group 2. The occurrence of an adverse event, such as death, reinfarction, or revascularization, either in hospital or after 6 or 12 months was recorded. Three patients experienced subacute stent thrombosis, all in group 2. No statistically significant difference in any other variable was found. The combined rate of death, reinfarction, revascularization, or rehospitalization at 12 months was 14% in group 1 and 16% in group 2 (P=.7). Carrying out cardiac magnetic resonance imaging shortly after stent implantation in acute myocardial infarction patients appears to be a safe procedure.


Effect of prednisolone on hormone profiles during primary endocrine treatment of advanced breast cancer.
Various plasma hormones were measured in 13 pre- and 20 post-menopausal women with advanced breast cancer before and for 12 months after ovarian irradiation or during continuous administration of tamoxifen at a dose of 10 mg twice a day, respectively; some patients received additional prednisolone at a dose of 5 mg twice a day. These patients were taken from a larger clinical trial which demonstrated a higher response to primary endocrine therapy when prednisolone was added. Levels of dehydropiandrosterone sulfate were depressed in patients receiving prednisolone, confirming adrenal suppression. Estradiol levels were reduced in all patients, while luteinizing hormone and follicular stimulating hormone increased after ovarian irradiation, but all three hormones fell during tamoxifen administration; no further changes were caused by the addition of prednisolone. Prolactin and thyroxine remained constant throughout the study. There were no differences between responders and nonresponders in hormone profiles or in changes in the profiles after treatment.


Experimental studies of psychophysiological factors in sudden cardiac death.
Earlier research in the field of sudden cardiac death is reviewed. Such studies have largely oriented towards the provocation of myocardial injury and asystole in normal animals. However, such investigations constitute an inadequate model to describe the clinical appearance of sudden death, where underlying coronary disease is often present and the precipitating event is usually ventricular fibrillation rather than asystole. This report describes a series of studies designed to investigate the processes underlying cardiac vulnerability and the influence upon it of various psychological stresses. It is concluded that the primary mediator of ventricular vulnerability is the sympathetic nervous system. The efferent vagus appears to exert some protective influence against arrhythmias due to adrenergic stimulation. An appropriate clinical strategy for the treatment of malignant arrhythmias would therefore involve attempts to decrease cardiac sympathetic drive whilst at the same time enhancing vagal tone. Treatments are described which aim to bring this situation about by the use of clonidine, morphine sulphate, l-tryptophan and tyrosine. The use of neurochemical agents in this context appears promising.


Unanswered Questions Regarding Blood Pressure Management for HF Prevention.
Evaluate the relevant new findings regarding hypertension treatment and heart failure prevention published in the past 3 years. In a recent secondary analysis of Systolic Blood Pressure Intervention Trial (SPRINT), randomization of more than 9000 patients > 50 years old with high cardiovascular risk but without diabetes to intensive treatment targeting blood pressure < 120/80 mmHg compared to standard treatment targeting < 140/90 mmHg significantly reduced incident heart failure. While such benefits outweighed potential harm, adverse events including renal dysfunction, hypotension, and syncope occurred more frequently with intensive treatment. Following SPRINT, existing guidelines differ in their recommendations and controversies still exist. Key persistent questions include the role of intensive treatment in younger adults and those at lower cardiovascular risk and optimal approaches to translate clinical trial findings into clinical practice in a sustainable fashion. Aggressively treating hypertension to targets below 120/80 mmHg prevents heart failure in high-risk patients. However, evidence is lacking to younger patients and those at lower cardiovascular risk.


Melioidosis Cases and Selected Reports of Occupational Exposures to Burkholderia pseudomallei--United States, 2008-2013.
Melioidosis is an infection caused by the Gram-negative bacillus Burkholderia pseudomallei, which is naturally found in water and soil in areas endemic for melioidosis. Infection can be severe and sometimes fatal. The federal select agent program designates B. pseudomallei as a Tier 1 overlap select agent, which can affect both humans and animals. Identification of B. pseudomallei and all occupational exposures must be reported to the Federal Select Agent Program immediately (i.e., within 24 hours), whereas states are not required to notify CDC's Bacterial Special Pathogens Branch (BSPB) of human infections. 2008-2013. The passive surveillance system includes reports of suspected (human and animal) melioidosis cases and reports of incidents of possible occupational exposures. Reporting of suspected cases to BSPB is voluntary. BSPB receives reports of occupational exposure in the context of a request for technical consultation (so that the system does not include the full complement of the mandatory and confidential reporting to the Federal Select Agent Program). Reporting sources include state health departments, medical facilities, microbiologic laboratories, or research facilities. Melioidosis cases are classified using the standard case definition adopted by the Council of State and Territorial Epidemiologists in 2011. In follow up to reports of occupational exposures, CDC often provides technical assistance to state health departments to identify all persons with possible exposures, define level of risk, and provide recommendations for postexposure prophylaxis and health monitoring of exposed persons. During 2008-2013, BSPB provided technical assistance to 20 U.S. states and Puerto Rico involving 37 confirmed cases of melioidosis (34 human cases and three animal cases). Among those with documented travel history, the majority of reported cases (64%) occurred among persons with a documented travel history to areas endemic for melioidosis. Two persons did not report any travel outside of the United States. Separately, six incidents of possible occupational exposure involving research activities also were reported to BSPB, for which two incidents involved occupational exposures and no human infections occurred. Technical assistance was not required for these incidents because of risk-level (low or none) and appropriate onsite occupational safety response. Of the 261 persons at risk for occupational exposure to B. pseudomallei while performing laboratory diagnostics, 43 (16%) persons had high-risk exposures, 130 (50%) persons had low-risk exposures, and 88 (34%) persons were classified as having undetermined or unknown risk. A small number of U.S. cases of melioidosis have been reported among persons with no travel history outside of the United States, whereas the majority of cases have occurred in persons with a travel history to areas endemic for melioidosis. If the number of travelers continues to increase in countries where the disease is endemic, the likelihood of identifying imported melioidosis cases in the United States might also increase. Reporting of melioidosis cases can improve the ability to monitor the incidence and prevalence of the disease in the United States. To improve prevention and control of melioidosis, CDC recommends that (1) physicians consider melioidosis in the differential diagnosis of patients with acute febrile illnesses, risk factors for melioidosis, and compatible travel or exposure history; (2) personnel at risk for occupational exposure (e.g., laboratory workers or researchers) follow proper safety practices, which includes using appropriate personal protective equipment when working with unknown pathogens; and (3) all possible occupational exposures to B. pseudomallei be reported voluntarily to BSPB.


[Hepatocyte transplantation].
Transplantation of hepatocytes is considered a promising technology for the cell therapy of liver diseases. Cells are isolated from donor livers, which are not allocated for organ transplantation and transplanted into the liver of a suitable recipient. Ideally, the transplanted cells functionally replace the hepatocytes of the diseased organ and restore its metabolic capacity either permanently or for a period of bridging to organ transplantation. Although about 50 cases of clinical hepatocyte transplantation have been documented, therapeutic benefit is doubtful, and the reasons for this are largely unknown. Minor quality of the transplanted cells isolated from marginal donor livers may be a major cause. Therefore, animal models have been established, which enable scientists to develop novel procedures of hepatocyte transplantation and to specifically study the mechanisms of hepatocyte integration in the host liver. Hopefully, results generated in animal models will set the basis for the design of novel procedures of hepatocyte transplantation individualized to the underlying disease in order to provide a growth advantage for donor over host cells. The plasticity of stem cells and their proliferative potential is the basis for current efforts to generate stem cell-derived hepatocytes of transplantation quality for the treatment of liver diseases.


Layered double hydroxides as flame retardant and thermal stabilizer for polymers.
Layered double hydroxides (LDH) has wide applications as non-toxic and halogen-free flame retardant for various resins and highly efficient thermal stabilizer for halogen-containing polymers. This review will discuss some public patents and relevant papers on the flame retardancy and the thermal stability of LDH/polymer composites when the LDHs with different chemical compositions are used as the additive in the polymer matrix. We have summarized these related LDHs in two tables: one for flame retardant and the other for thermal stabilizer.


Role of tissue repair in survival from s-(1,2-dichlorovinyl)-L-cysteine-induced acute renal tubular necrosis in the mouse.
S-(1,2-Dichlorovinyl)-L-cysteine (DCVC), a model nephrotoxicant in mice, causes acute tubular necrosis and death at high doses. Our earlier studies revealed that renal tissue repair was critical for survival in mice with DCVC nephrotoxicity. The objective of this study was to investigate if increasing renal tissue repair could protect mice from the lethal outcome of DCVC. Male Swiss Webster (SW) mice were administered a low dose of DCVC (15 mg/kg, ip) 72 h before injection of a normally lethal dose of DCVC (75 mg/kg, ip); this resulted in 100% protection against the lethal effect of DCVC. Because DCVC caused approximately two fold decrease in cytosolic and mitochondrial beta-lyase activity, the possibility that DCVC protection may be caused by decreased bioactivation was examined. Mercuric chloride (HgCl2, 6 mg/kg), a nephrotoxicant with no effect on beta-lyase activity, was administered 96 h before a lethal dose of DCVC. This also resulted in 100% protection from the lethal effect of DCVC. In both studies total glutathione was unchanged at any time after the lethal dose of DCVC was administered, obviating the role of glutathione in protection. In both cases the augmented and sustained tissue repair induced by priming dose and documented by 3H-thymidine pulse labeling and immunocytochemistry for proliferating cell nuclear antigen resulted in 100% survival in spite of the extensive renal injury. These findings suggest that stimulation of renal tubular repair by the priming dose, through augmented cell division, and the resistance of new cells to mechanisms of progression of injury, underlies auto- and heteroprotection against DCVC. The molecular mechanisms may have potential application in pharmacotherapeutic intervention for treatment of acute renal failure.


Monomer adsorption on equilateral triangular lattices with attractive first-neighbor interactions.
We have recently studied a model of monomer adsorption on infinitely long equilateral triangular lattices with terraces of finite width M and nonperiodic boundaries. This study was restricted to the case of repulsive adsorbate-adsorbate first-neighbor interactions but included attractive, repulsive, and negligible second-neighbor interactions. The present work extends this study to the case of attractive first-neighbors, and the phases are determined, as before, with a confidence exceeding 10 significant figures. Phase diagrams are included for terrace widths M < or =11. Most of the occupational characteristics of the phases fit exact analytic expressions in M. The infinite-M limit of these expressions, combined with other analyses, provide the complete phase diagram for the infinite two-dimensional lattice. In addition to the empty and full coverage phases, there are three phases exhibiting stripe and cluster features that were not observed in the case of repulsive first-neighbors.


Clinical manifestations and audiologic diagnosis of acoustic neuromas.
If an AN is suspected, a detailed patient history and a thorough otologic and neurotologic physical examination should be carried out. The first echelon of diagnostic testing begins with a pure tone audiogram, speech reception threshold, speech discrimination testing, and acoustic reflex testing. If the clinician is even moderately suspicious of the presence of an AN, the patient should undergo a Gd-MRI scan. If suspicion is low, an ABR should be performed, and if negative, the patient should be reevaluated periodically.


Laser disruption and killing of methicillin-resistant Staphylococcus aureus biofilms.
The aim of the study was to study the efficacy of 2 different lasers in vitro, in disrupting biofilm and killing planktonic pathogenic bacteria. Biofilms of a stable bioluminescent of Staphylococcus aureus Xen 31 were grown in a 96-well microtiter plate for 3 days. The study included 7 arms: (a) control; (b) ciprofloxacin (3 mg/L, the established minimum inhibitory concentration [MIC]) alone; (c) shock wave (SW) laser alone; (d) near-infrared (NIR) laser alone; (e) SW laser and ciprofloxacin; (f) SW and NIR lasers; (g) SW, NIR lasers, and ciprofloxacin. The results were evaluated with an in vivo imaging system (IVIS) biophotonic system (for live bacteria) and optical density (OD) for total bacteria. Without antibiotics, there was a 43% reduction in OD (P < .05) caused by the combination of SW and NIR suggesting that biofilm had been disrupted. There was an 88% reduction (P < .05) in live biofilm. Ciprofloxacin alone resulted in a decrease of 28% of total live cells (biofilm remaining attached) and 58% of biofilm cells (both P > .05). Ciprofloxacin in combination with SW and SW + NIR lasers caused a decrease of more than 60% in total live biomass and more than 80% of biofilm cells, which was significantly greater than ciprofloxacin alone (P < .05). We have demonstrated an effective nonpharmacologic treatment method for methicillin-resistant Staphylococcus aureus (MRSA) biofilm disruption and killing using 2 different lasers. The preferred treatment sequence is a SW laser disruption of biofilm followed by NIR laser illumination. Treatment optimization of biofilm is possible with the addition of ciprofloxacin in concentrations consistent with planktonic MIC.


The European standard on planetary protection requirements.
Since the beginning of solar system exploration, numerous spacecrafts have been sent towards others worlds, and one of the main goals of such missions is the search for extraterrestrial forms of life. It is known that, under certain conditions, some terrestrial entities are able to survive during cruises in space and that they may contaminate other planets (forward contamination). At another level, possible extraterrestrial life forms are unknown and their ability to contaminate the Earth's biosphere (back contamination) in the frame of sample return missions cannot be excluded. Article IX of the Outer Space Treaty (London/Washington, January 27, 1967) requires the preservation of planets and the Earth from contamination. All nations taking part in this Treaty must prevent forward and back contamination during missions exploring our solar system. Consequently, the United Nations (UN-COPUOS) has delegated COSPAR (Committee of Space Research) to take charge of planetary protection and, at present, all space-faring nations must comply with COSPAR policy and consequently with COSPAR planetary protection recommendations. Starting from these recommendations and the "CNES Planetary Protection Standard" document, a working group has been set up in the framework of the "European Cooperation for Space Standardization" (ECSS) to establish the main specifications for preventing cross-contamination between target bodies within the solar system and the Earth-moon system.


Administration of 25,000 IU vitamin A doses at routine immunisation in young infants.
To investigate whether monthly administration of vitamin A at routine immunisation produces any side-effects, and to examine the effect of this supplementation on the vitamin A nutrition status of infants. A double-blind randomised placebo-controlled clinical trial. Immunisation clinic of a large diarrhoea treatment centre. Infants aged 6-17 weeks who will receive their first diphtheria-pertussis-tetanus/oral polio vaccine (DPT/OPV) dose. Infants were randomly assigned to receive either 25,000 IU vitamin A or placebo. Three such doses were given with each immunisation dose at monthly intervals. Infants were examined by a physician before and during 24 h after the doses and any signs of toxicity were recorded. Venous blood was drawn at entry and 1 month after the 3rd dose for retinol assay. One hundred and one infants received vitamin A and 98 received placebo. Decreased feeding, irritability, diarrhoea, and vomiting were comparable between the two groups. In the vitamin A group five infants developed bulging fontanelle; three of them developed it once (after 1st, 2nd and 3rd dose respectively), one developed it twice (after both the 2nd and 3rd dose), and the other infant after all three doses. In the placebo group a single child developed bulging fontanelle after the 3rd dose. In all the cases the bulging disappeared within 48 h of onset except in one infant, in whom it subsided at 60 h. The total bulging episodes in the vitamin A and placebo groups were 8 and 1 respectively (RR = 7.7; P < 0.04). However, none of these infants had irritability. At entry fasting retinol level was < 10 micrograms/dl in 35% infants and in 87% infants it was < 20 micrograms/dl. After the third dose fasting retinol level was marginally better in the vitamin A group (mean +/- s.d.: 21.9 +/- 8.2 vs 19.2 +/- 7.8; P = 0.05). However, 47% infants receiving supplementation still had serum retinol level <20 micrograms/dl. The results suggest that administration of 25,000 IU of vitamin A in young infants along with routine immunisations, though associated with increased incidence of transient bulging fontanelle without any associated adverse signs or symptoms, may still be inadequate to prevent deficiency in this population. This study was funded by the United States Agency for International Development (USAID) under grant no. DPE-5986-A-1009-00 with the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B). The ICDDR,B is supported by countries and agencies which share its concern for the health problems of developing countries.


Therapeutic effects of heme oxygenase-1 on psoriasiform skin lesions in guinea pigs.
Heme oxygenase-1 (HO-1) has been shown to exert immunosuppressive, anti-inflammatory, anti-apoptotic and anti-proliferative effects. Its unique positive effects indicate that this enzyme might be a potential therapeutic target for psoriasis. To determine the effect of pharmacologic up-regulation of HO-1 on psoriasis, we generated a guinea pig model of psoriasiform skin lesions using propranolol induction. In this in vivo model, the 3-week propranolol challenge generated the psoriasiform pathological changes on the ears of guinea pigs. And then, guinea pigs were intraperitoneally injected with 5 mg/kg cobalt protoporphyrin (CoPP), a potent HO-1 inducer, 20 mg/kg zinc protoporphyrin, an inhibitor of HO-1, or PBS as controls, once a week from 9 weeks of age to 14 weeks old. CoPP induced notably HO-1 expression at both mRNA and protein levels. Moreover, CoPP treatment led to a significant reduction of the psoriasiform histopathological changes and remarkable amelioration of the psoriasiform skin lesions, compared with PBS treatment, with a concomitant reduction in proliferating cell nuclear antigen expression. Additionally, CoPP treatment resulted in a decreased TNF-alpha and significantly increased IL-10 release. Our results suggest that HO-1 induction therapy ameliorates the psoriasiform skin lesions by suppressing keratinocyte hyperproliferation and attenuating production of inflammatory responses.


Intrinsic radiation sensitivity may not be the major determinant of the poor clinical outcome of glioblastoma multiforme.
Many radiobiologic mechanisms may contribute to the clinical radiation resistance of Glioblastoma Multiforme. One of them is considered to be an unusually low intrinsic radiation sensitivity. This is a collaborative study between three laboratories to evaluate the intrinsic radiation sensitivity of 85 cell lines derived from human malignant gliomas as the major cause of the poor clinical results of radiation treatment to these tumors. Fifty-one cell lines were early passage. The distribution by histologic type was: 58 glioblastoma, 17 anaplastic astrocytoma, six oligodendroglioma and four astrocytoma grade 2. The intrinsic radiation sensitivity will be expressed by the surviving fraction at 2 Gy (SF2). The SF2 has been determined for single dose irradiation for cell lines on exponential phase, under aerobic conditions, growing on plastic. The patient age, Karnofski Status, histological grade, survival, dose of irradiation for 50 patients are investigated for correlation with SF2 of the corresponding newly established cell lines. The mean SF2 of the 85 cell lines was 0.46 (0.12-0.87). The mean SF2 by histologic type was 0.50, 0.34, 0.54 and 0.38 for glioblastoma, anaplastic astrocytoma, oligodendroglioma and astrocytoma grade 2 cell lines, respectively. No correlation was found between SF2 and the patient age or Karnofski status. The difference in SF2 between the 58 glioblastoma and 17 anaplastic astrocytoma cell lines was significant p = 0.002. The difference in actuarial survival between glioblastoma and anaplastic astrocytoma patients was borderline of significance (p = 0.08). The difference in SF2 of cell lines derived from these two groups of patients was of borderline significance (p = 0.08). The difference in radiation sensitivity for anaplastic astrocytoma and glioblastoma cell lines was clearly reflected in the difference in survival for the two groups of patients from where the cell lines were derived. However, no correlation was found between SF2 and survival within each grade. In a multivariate analysis the age, grade and Karnofski status were found to be significant prognostic values for survival with a p values of 0.032, 0.03 and 0.038, respectively, however, the ln SF2 was not significant (p = 0.40). The mean SF2 of the 6 oligodendroglioma cell lines (0.54) was comparable to that of glioblastoma multiforme (0.50). The high SF2 for oligodendroglioma does not accord with the much better clinical outcome of these tumors. These data on 85 malignant glioma cell lines show a very broad distribution of SF2 values for irradiation in vitro. SF2 reflected the difference in sensitivity between AA (Grade 3) and GBM (Grade 4). This may suggest that the parameter SF2 is useful to discriminate between the sensitivity of different grades or types of histology in vitro. However, SF2 was not a predictor of the clinical outcome on individual basis for malignant gliomas. The in vitro studies will need to be supplemented by physiologic characterization of the tumors in vivo. Such conclusions would limit the predictive value of current radiation sensitivity assays based on in vitro dose-survival measurement for at least high grade malignant gliomas.


[MAC-TL twin screw. A new thoracoscopic implantable stabilization system for treatment of vertebral fractures--implant design, implantation technique and in vitro testing].
Due to the lack of an appropriate instrumentation system for minimally invasive procedures to treat spinal fracture, a new thoracoscopically implantable stabilization system was developed. This report describes the new implant design and implantation technique. In a biomechanical in vitro study, an anterior corpectomy model representing the worst case of burst fracture instability was simulated, and the primary stability parameters of the new system were evaluated in comparison to a dorsal stabilization system. With the interbody graft and fixation, the new system demonstrated higher stabilizing effects in flexion/extension and lateral bending and restored axial stability beyond the intact spine and the dorsal stabilization system. Considering all the advantages of the endoscopic procedure and this biomechanical characterization, the clinical trial is warranted; its usefulness has been demonstrated in more than 150 cases in a multicenter study to date.


Metabolizing enzyme genotype and risk for upper aerodigestive tract cancer.
Genetic polymorphisms are associated with a number of enzymes involved in the metabolism of carcinogens important in the induction of upper aerodigestive tract cancer. It has been suggested that such polymorphisms may be linked to cancer susceptibility. Using a case-control molecular epidemiologic approach, the association between many of these genetic polymorphisms and susceptibility to upper aerodigestive tract cancer has been investigated in numerous studies. In this review, we summarize the findings of these studies, analyzing potential associations with upper aerodigestive tract cancer risk in terms of gene:environment interactions, genotype-induced functional defects in enzyme activity and/or expression, and the influence of race on these associations.


Plasma levels of fat-soluble vitamins A and E in neonates, after administration of two different vitamin solutions.
The aim of this study was to compare the effects of 2 different vitamin solutions on plasma levels of vitamin A and E during and after short term total parenteral nutrition (TPN), after neonatal surgery. 2 compounds were compared, one with a higher vitamin A content (100 mu g/ml) and no vitamin E and one with vitamin E (0.64 mg/ml) and a lower vitamin A content (69 mu g/ml). 2 randomly chosen groups of 10 neonates were studied each with gastrointestinal malformations. The groups were comparable regarding gestational age (GA), weight and length. Diagnoses within the groups were similar. TPN was given after corrective surgery for a median time of 6.5 days to both groups. Vitamin A and retinol binding protein (RBP) levels increased significantly (p < 0.05) above the pre-treatment level in patients receiving supplementation with a higher dosage of vitamin A (100 mu g/ml). In patients receiving the lower dose of vitamin A (69 mu g/ml) plasma levels of this vitamin were unchanged but RBP levels fell significantly (p < 0.05). There was no significant difference in plasma vitamin E levels in the group of patients receiving vitamin E supplementation as compared with the unsupplemented group. In both groups vitamin E levels increased significantly (p < 0.005) after introduction of oral feeding. The results indicate that even during short term TPN endogenous stores of vitamin A might become depleted. In spite of the fact that no vitamin A deficiency was noted it seems obvious that a higher vitamin A intake is advisable which is in accordance with the recommendations from the Subcommittee on Paediatric Parenteral Nutrient Requirements from the Committee on Clinical Practice Issues of The American Society for Clinical Nutrition.


Effect of polyvinyl phosphonates and ethane hydroxy diphosphonate on mineralization of ectopic bone.
The effects of polymeric polyphosphonate and of ethane hydroxydiphosphonate on the development of ectopic bone were compared at different stages of bone development. The diphosphonate affected bone development at different stages, as reflected by alkaline phosphatase and aryl sulphatase activities, as well as by the creation of calcium ions by bone and on its readiness to undergo isotopic exchange. The polymeric polyphosphonate (mol. wt., 3500-8000), on the other hand, did not exhibit any of these effects, although it did inhibit the activity of the enzymes in vitro to an extent comparable with that of the diphosphonate. The results corroborate the assumption that the effects of polymeric polyphosphonates on hard tissues are confined to the extracellular space while the effects of diphosphonates on bone development are due to intracellular activity and not to sequestering of extracellular calcium.


A new score predicting intraprocedural risk in patients undergoing CT-guided percutaneous needle pulmonary biopsy (CATH-score).
To develop a new score (CATH-score) for predicting intra-procedural risk in patients undergoing CT-guided percutaneous needle pulmonary biopsy. 100 CT-guided lung biopsies performed with a 18 Gauge (G) needle (Pilot Group) were reviewed to analyse patient-, lesion- and procedure-related variables to identify risk factors for procedural complications (pneumothorax and parenchymal bleeding) and diagnosis failure. A scoring system for predicting complications and choosing the right needle (16 G, 18 G, 21 G) was developed using risk factors weighting and prospectively applied to 153 consecutive biopsies (CATH-score Group); complications and diagnostic rates obtained were compared with a group of patients (Control Group) that underwent lung biopsy; in this group of patients the choice of the calliper of the needle was based on the operator experience. lesion diameter (p=0.03), central location of lesion (p=0.02), centrilobular emphysema (p=0.04) and trans-pulmonary needle route (p=0.002) were associated with a higher complications rate in Pilot Group and were selected as risk factors to include in the CATH-score definition. Risk factors "cut-off" values were identified (Receiver Operating Characteristics curves) and risk-stratification groups were classified as follows: low (16 G, score 1), intermediate (18 G, score 2), and high procedural risk score (21 G, score 3). CATH-score usage limited complications rate despite a higher number of 16 G needle employed, with a diagnostic performance rising respect to Control Group. CATH-score seems to be a valuable tool for predicting the risk of complications and choosing the right needle, in order to increase diagnostic performance in patients undergoing TTNA.


Hemocompatibility testing according to ISO 10993-4: discrimination between pyrogen- and device-induced hemostatic activation.
Next to good hemocompatibility performance of new medical devices, which has to be tested according to the ISO 10993-4, the detection of pyrogen-contaminated devices plays a pivotal role for safe device application. During blood contact with pyrogen-contaminated devices, intense inflammatory and hemostatic reactions are feared. The aim of our study was to investigate the influence of pyrogenic contaminations on stents according to the ISO 10993-4. The pyrogens of different origins like lipopolysaccharides (LPS), purified lipoteichoic acid (LTA) or zymosan were used. These pyrogens were dried on stents or dissolved and circulated in a Chandler-loop model for 90 min at 37°C with human blood. Before and after circulation, parameters of the hemostatic system including coagulation, platelets, complement and leukocyte activation were investigated. The complement system was activated by LPS isolated from Klebsiella pneumoniae and Pseudomonas aeruginosa and by LTA. Leukocyte activation was triggered by LPS isolated from K. pneumoniae, LTA and zymosan, whereas coagulation and platelet activation were only slightly influenced. Our data indicate that pyrogen-contaminated devices lead to an alteration in the hemostatic response when compared to depyrogenized devices. Therefore, pyrogenicity testing should be performed prior to hemocompatibility tests according to ISO 10993-4 in order to exclude hemostatic activation induced by pyrogen contaminations.


The survival time post-cecal ligation and puncture in sinoaortic denervated rats.
Arterial baroreflex (ABR) function is an important determinant factor in prognosis of many cardiovascular diseases. The present work was designed to study the relationship between ABR function and the survival time of septic shock in a cecal ligation and puncture (CLP) rat model. The dysfunction of ABR was introduced by sinoaortic denervation (SAD). It was found that the survival time after CLP was significantly reduced in SAD rats compared with sham-operated rats (12.7 +/- 2.92 hours versus 15.0 +/- 4.01 hours; P < 0.05). Furthermore, significant differences were also seen when the results were expressed by Kaplan-Meier survival curves. Compared with the baseline values, both noradrenaline and adrenaline significantly increased in both SAD and Sham groups after CLP, but we found the baseline of noradrenaline was significantly elevated in SAD rats. In addition, the TNF-alpha, noradrenaline, and adrenaline levels of the SAD group were significantly higher than those of the Sham group at 5 hours post-CLP. In conclusion, the present work demonstrates that ABR function was related to the survival time in CLP-induced lethal shock model. The loss of inhibition in the sympathetic activity and in the release of some inflammatory cytokines during CLP-induced septic shock related to baroreflex and/or chemoreflex dysfunction may be the mechanisms involved in the poorer prognosis in septic shock.


The role of overweight and obesity in calcium oxalate stone formation.
The aim of the study was to assess the influence of overweight and obesity on the risk of calcium oxalate stone formation. BMI, 24-hour urine, and serum parameters were evaluated in idiopathic calcium oxalate stone formers (363 men and 164 women) without medical or dietetic pretreatment. Overweight and obesity were present in 59.2% of the men and in 43.9% of the women in the study population. Multiple linear regression analysis revealed a significant positive relationship between BMI and urinary uric acid, sodium, ammonium, and phosphate excretion and an inverse correlation between BMI and urinary pH in both men and women, whereas BMI was associated with urinary oxalate excretion only among women and with urinary calcium excretion only among men. Serum uric acid and creatinine concentrations were correlated with BMI in both genders. Because no association was established between BMI and urinary volume, magnesium, and citrate excretion, inhibitors of calcium oxalate stone formation, the risk of stone formation increased significantly with increasing BMI among both men and women with urolithiasis (p = 0.015). The risk of calcium oxalate stone formation, median number of stone episodes, and frequency of diet-related diseases were highest in overweight and obese men. Overweight and obesity are strongly associated with an elevated risk of stone formation in both genders due to an increased urinary excretion of promoters but not inhibitors of calcium oxalate stone formation. Overweight and obese men are more prone to stone formation than overweight women.


Cervical pharyngostomy: an alternative approach to enteral feeding.
Surgical patients may be unable or unwilling to feed normally, owing to mechanical obstruction to ingestion because of nausea or anorexia or secondary to neurologic abnormality. Such patients may be in a malnourished state that compromises their chances of successful recovery. The Nasogastric tube (NGT) has been the standard method of postoperative alimentation in head and neck cancer patients. However, prolonged use of an NGT has been associated with many problems. Percutaneous endoscopic gastrotomy (PEG) tubes are generally easier to manage and more esthetically pleasing than NGTs. However, they are associated with their own set of shortcomings. Problems and complications with traditional NGT led us to evaluate feeding tubes placed through a cervical pharyngostomy. We present our experience with this technique in 15 patients in whom it was used for postoperative feeding after oropharyngeal cancer resection and reconstruction. The cervical pharyngostomy technique has proven to be a safe, reliable, cost-effective and convenient method for postoperative feeding.


Common mental disorder including psychotic experiences: Trailblazing a new recovery pathway within the Improving Access to Psychological Therapies programme in England.
Psychotic experiences, depressive and anxiety symptoms may be manifestations of a latent continuum of common mental distress. The Improving Access to Psychological Therapies (IAPT) programme has increased the reach of psychological treatments to people with common mental disorders in England. However, psychotic experiences are neither measured nor considered in therapy. We aimed to confirm the presence of psychotic experiences among IAPT service-users and determine whether these experiences are associated with higher depression/anxiety levels and poorer recovery. All service-users that attended the Fenland and Peterborough IAPT teams in Cambridgeshire between November 16, 2015 and January 29, 2016 participated in a service evaluation. In addition to routine mesures, such as the Generalized Anxiety Disorder-7 questionnaire (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9), we introduced a shortened version of the Community Assessment of Psychic Experiences (CAPE-P15) to measure psychotic experiences. Classes of individuals were identified with latent class analysis. Associations were reported using Pearson correlation coefficient. One hundred and seventy-three services-users were included, mostly females (N = 133; 76.9%). The mean age was 36.6 (SD = 13.3). Around 30% likely belonged to a class with psychotic experiences. CAPE-P15 frequency was significantly correlated to PHQ-9 (r = 0.44; P < .001) and GAD-7 (r = 0.32; P < .001). Similarly, CAPE-P15 distress and both PHQ-9 (r = 0.43; P < .001) and GAD-7 (r = 0.38; P < .001) were highly correlated. These associations were replicated after the initial period of the therapy, indicating poor recovery. Some IAPT service-users suffer psychotic experiences. Tailoring available evidence-based psychological therapies for these people in IAPT settings might trailblaze a new care pathway to improve recovery in this group.


Perception and the awareness of God: the importance of neuronal habituation in the context of the Jewish and Christian faiths.
One of the most significant existential dilemmas for the religious person is the discrepancy between the assertion that God is everywhere and eternally present, and the inability to become aware of His presence. In this paper, we discuss how developments in our understanding of the brain's mechanisms for perception may resolve this apparent contradiction. We submit that if God is eternally present and unchangeable, then by the process of neuronal habituation, an individual can be "unaware" of the presence of God. We also discuss the limits of human perception and illustrate the biblical questions concerning the awareness of God.


Subgroup differences in having a usual source of health care among working-age adults with and without disabilities.
Having a usual source of health care is positively associated with regular health maintenance visits and receipt of preventive services. People with disabilities are, overall, more likely than those without disabilities to have a usual source of care (USC). However, the population of people with disabilities is quite heterogenous, and some segments of the population may have less access to a USC than others. To determine whether there are significant subgroup differences in having a USC within the U.S. population of working-age adults with disabilities, and to compare adults with and without disabilities while controlling for other subgroup differences. We analyzed Medical Expenditure Panel Survey annual data files from 2002 to 2008. We performed both bivariate and multivariate logistic regression analyses to examine the relationship of sociodemographic and disability subgroup variables with having a USC. Within the disability population, individuals who were younger; male; Black, Hispanic, or other (non-White) race; less educated; of lower income; or uninsured for part or all of the year were significantly less likely to have a USC. These differences mirrored those among adults without disabilities. When controlling for these differences, people with physical, hearing, or multiple disabilities had greater odds of having a USC than people without disabilities, but those with vision or cognitive limitations did not differ significantly from the non-disabled referent group. Disparities among people with and without disabilities are similar, underscoring the need for attention to disparities within the disability population.


Training pathways for careers in dental, oral, and craniofacial research.
There are virtually unlimited opportunities for biomedical research training through either extramural or intramural training mechanisms, with programs designed for both the pre- and postdoctoral educational levels. The only difficulty is selecting from the vast array of research topic areas.


Statins and direct vascular actions.
Statins can exert many pleiotropic effects beyond their cholesterol-lowering action. These effects mainly influence the vascular wall and may modulate beneficially endothelial function, atherogenesis and atherosclerotic plaque stability. Recent data suggest a possible positive effect of statins on prevention of osteoporosis and cancerogenesis. However, the magnitude of contribution of these pleiotropic statin effects to the reduction of morbidity and mortality of cardiovascular diseases remains to be determined.


Comet Assay measurements: a perspective.
The Comet Assay or single cell gel electrophoresis assay is one of the very widely used assays to microscopically detect DNA damage at the level of a single cell. The determination of damage is carried out either through visual scoring of cells (after classification into different categories on the basis of tail length and shape) or by using different commercially available or public domain software (which automatically recognise the extent of damage). In this assay, the shape, size and amount of DNA within the 'comet' play important roles in the determination of the level of damage. The use of a software in particular also provides a range of different parameters, many of which might not be relevant in determining the extent of DNA damage. As a large number of factors could influence the shape, size, identification and determination of induced damage, which includes the scoring criteria, staining techniques, selection of parameters (whilst using the software packages) and appearance of 'hedgehog' or 'clouds', this article aims (a) to provide an overview of evolution of measurements of DNA damage using the Comet Assay and (b) to summarise and critically analyse the advantages and disadvantages of different approaches currently being adopted whilst using this assay. It is suggested that judicious selection of different parameters, staining methods along with inter-laboratory validation and harmonisation of methodologies will further help in making this assay more robust and widely acceptable for scientific as well as regulatory studies.


Trichinella pseudospiralis secretes a protein related to the Trichinella spiralis 43-kDa glycoprotein.
A 43-kDa secreted glycoprotein from the intracellular parasitic nematode Trichinella spiralis has been considered as a factor involved in the formation of the Nurse cell in infected muscle. The closely related intracellular parasitic nematode Trichinella pseudospiralis that also infects muscle cells, does not form Nurse cells and was thought not to secrete the 43-kDa glycoprotein. This implied a unique role for the 43-kDa glycoprotein in T. spiralis infection and supported the hypothesis of involvement of the 43-kDa glycoprotein in Nurse cell formation. Following cloning of a full length cDNA encoding the 43-kDa protein, antibodies were raised against several domains of the 43-kDa glycoprotein. Here we show that a protein related to the 43-kDa glycoprotein exists in T. pseudospiralis. Immunohistochemical studies reveal important similarities in the distribution of the 43-kDa glycoprotein and the related protein from T. pseudospiralis in muscle infections with either of the two parasites. The 43-kDa glycoprotein may therefore play a common role in the life cycles of these two parasites and probably is not involved in Nurse cell formation.


Behavioural mechanisms affecting energy regulation in mice prone or resistant to diet- induced obesity.
We investigated inbred SWR/J and AKR/J mice, two established models for different susceptibility to diet-induced obesity (DIO), to scrutinize the contribution of physical activity and energy assimilation to the etiology of developing obesity. Body mass gain and body composition of mice fed a high-energy (HE) or a low caloric control diet were monitored. In parallel, assimilated energy, locomotor activity and thermoregulatory behaviour were measured. Activity was continuously registered by radio telemetry and, in addition, Open Field (OF) behaviour was used as a quick screening tool for spontaneous activity before and after the feeding trial. Energy assimilation was increased in both strains on HE (AKR/J: +60.7% and SWR/J: +42.8%) but only in AKR/J, body mass (+8.1%) and fat mass (+40.7%) were significantly elevated. As a trend, total home cage activity was increased and was more scattered in SWR/J. Interestingly, HE stimulated OF activity only in SWR/J in the second trial at the end of the feeding experiment. The spatial pattern of OF activity also differed between strains with obese mice avoiding the core area. Under housing conditions, nest building behaviour was more pronounced in AKR/J. To further evaluate OF behaviour as a marker for spontaneous activity an obese mouse line was investigated. Mice lacking the leptin receptor (db/db) showed already before the onset of obesity lowest activity levels in OF. Adjustment of energy intake, higher activity levels and energy consuming thermoregulatory behaviour are mechanisms employed by SWR/J mice to dissipate excess energy as a defence against the onset of obesity. Therefore our results deciphering mechanisms of DIO-sensitivity in mice contribute to the understanding of inter-individual differences in body weight development in an adipogenic environment.


Postural modulation of soleus H-reflex under simulated hypogravity by head-out water immersion in humans.
To test our hypothesis that somatosensory inputs would influence postural modulation of soleus H-reflex, eleven subjects were investigated under the head-out water immersion (HOWI) conditions. Subjects were supine or standing on a tilting bed in each condition. They were instructed to maintain an upright posture with both legs. The water was filled to the subject's neck level in a test tank to reduce 95% of the gravitational effect by buoyancy. Surface electromyography of the soleus and tibialis anterior was measured. The soleus H-reflex was elicited at a stimulation intensity of 1.05 times the motor threshold. The recruitment profile of the motor response was unchanged between the conditions. The background activities of the soleus and tibialis anterior were not detected in any condition. The peak-to-peak amplitude of the H-reflex was significantly different between the conditions while the stimulation intensity (small M size) was not different. The soleus H-reflex during standing was significantly decreased compared with being supine in the control condition, whereas it did not in the HOWI condition. It was concluded that somatosensory inputs due to gravity exert an influence on postural modulation of the soleus H-reflex to maintain static posture in humans.


Hydrochlorothiazide Increases Efferent Glomerular Arteriolar Resistance in Spontaneously Hypertensive Rats.
BACKGROUND: Micropuncture studies were performed to determine the intrarenal hemodynamic effects of two conventional antihypertensive agents, hydrochlorothiazide (HCTZ) and hydralazine (HYDR) alone and in combination. METHODS AND RESULTS: Male spontaneously hypertensive and normotensive Wistar Kyoto rats (19 weeks old) were treated for 3 weeks with vehicle (control), HCTZ (80 mg/kg/d), HYDR (5 mg/kg/d), or combined therapy (HCTZ 30 mg/kg/d and HYDR 2 mg/kg/d). Each treatment significantly reduced arterial pressure while effective renal plasma flow, glomerular filtration rate and single nephron glomerular filtration rate were unaffected by any treatment in either strain. In spontaneously hypertensive rats HCTZ decreased single nephron plasma flow (111 +/- 8 to 84 +/- 4 nL/min; P <.05) but, despite this reduction, glomerular pressure remained unchanged (51.4 +/- 0.7 to 52.1 +/- 0.8 mmHg) attributable to increased efferent glomerular resistance (1.58 +/- 0.14 to 2.11 +/- 0.12 10 U; P <.05). By contrast, HYDR increased single nephron plasma flow (to 147 +/- 8 nL/min; P <.01) and decreased efferent glomerular resistance (to 1.09 +/- 0.09 U; P <.05). Combined treatment produced responses similar to HCTZ when used alone, thereby nullifying the beneficial efferent glomerular resistance effects: single nephron plasma flow +/- fell (to 89 +/- 7 nL/min; P <.05) and efferent glomerular resistance increased (to 2.05 +/- 0.17 U; P <.05). In Wistar Kyoto rats, HCTZ and combined treatment had no effect. HCTZ alone induced glomerular ischemia that was associated with efferent glomerular arteriolar constriction in these spontaneously hypertensive rats. CONCLUSIONS: These findings provide a possible explanation for the lack of improved renal target-organ damage in controlled multicenter trials employing thiazide diuretics.


Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients.
The risk of cytomegalovirus (CMV) infection in solid organ transplant recipients has resulted in the frequent use of prophylaxis with the aim of preventing the clinical syndrome associated with CMV infection. This is an update of a review first published in 2005 and updated in 2008. To determine the benefits and harms of antiviral medications to prevent CMV disease and all-cause mortality in solid organ transplant recipients. We searched MEDLINE, EMBASE and the Cochrane Central Registry of Controlled Trials (CENTRAL) in The Cochrane Library to February 2004 for the first version of this review. The Cochrane Renal Group's specialised register was searched to February 2007 and to July 2011 for the first and current updates of the review without language restriction. We included randomised controlled trials (RCTs) and quasi-RCTs comparing antiviral medications with placebo or no treatment, comparing different antiviral medications and comparing different regimens of the same antiviral medications in recipients of any solid organ transplant. Studies examining pre-emptive therapy were excluded. Two authors independently assessed study eligibility, risk of bias and extracted data. Results were reported as risk ratios (RR) or risk differences (RD) with 95% confidence intervals (CI) for dichotomous outcomes and by mean difference (MD) with 95% CI for continuous outcomes. Statistical analyses were performed using the random-effects model. Subgroup analysis and univariate meta-regression were performed using restricted maximum-likelihood to estimate the between study variance. Multivariate meta-regression was performed to investigate whether the results were altered after allowing for differences in drugs used, organ transplanted, and recipient CMV serostatus at the time of transplantation. We identified 37 studies (4342 participants). Risk of bias attributes were poorly performed or reported with low risk of bias reported for sequence generation, allocation concealment, blinding and selective outcome reporting in 25% or fewer studies.Prophylaxis with aciclovir, ganciclovir or valaciclovir compared with placebo or no treatment significantly reduced the risk for CMV disease (19 studies; RR 0.42, 95% CI 0.34 to 0.52), CMV infection (17 studies; RR 0.61, 95% CI 0.48 to 0.77), and all-cause mortality (17 studies; RR 0.63, 95% CI 0.43 to 0.92) primarily due to reduced mortality from CMV disease (7 studies; RR 0.26, 95% CI 0.08 to 0.78). Prophylaxis reduced the risk of herpes simplex and herpes zoster disease, bacterial and protozoal infections but not fungal infection, acute rejection or graft loss.Meta-regression showed no significant difference in the relative benefit of treatment (risk of CMV disease or all-cause mortality) by organ transplanted or CMV serostatus; no conclusions were possible for CMV negative recipients of negative organs.Neurological dysfunction was more common with ganciclovir and valaciclovir compared with placebo/no treatment. In direct comparison studies, ganciclovir was more effective than aciclovir in preventing CMV disease (7 studies; RR 0.37, 95% CI 0.23 to 0.60) and leucopenia was more common with aciclovir. Valganciclovir and IV ganciclovir were as effective as oral ganciclovir. The efficacy and adverse effects of valganciclovir/ganciclovir did not differ from valaciclovir in three small studies. Extended duration prophylaxis significantly reduced the risk of CMV disease compared with three months therapy (2 studies; RR 0.20, 95% CI 0.12 to 0.35). Leucopenia was more common with extended duration prophylaxis but severe treatment associated adverse effects did not differ between extended and three month durations of treatment. Prophylaxis with antiviral medications reduces CMV disease and CMV-associated mortality in solid organ transplant recipients. These data suggest that antiviral prophylaxis should be used routinely in CMV positive recipients and in CMV negative recipients of CMV positive organ transplants.


[Effect utilization of diphosphonates at various types of restriction of impellent activity at animals].
The preventive effect of diphosphonates and vitamin D3 was studied at hypok[nesias and hypodynames. The received testify to the expressed preventive effect of disphosphonates on a condition of a bone status and a mineral exchange at animals at various kinds of modeling of effects of weightlessness.


Diffuse melanosis secondary to metastatic malignant melanoma. Light and electron microscopic findings.
Tumor-free hyperpigmented skin from a patient with diffuse melanosis secondary to metastatic melanoma was examined by light and electron microscopy. Our findings indicate that the pathogenesis of this diffuse slate blue color is primarily to pigment deposition within perivascular dermal macrophages. We did not find intact melanosomes or individual tumor cell metastases in clinically normal skin, as has been previously reported.


The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis.
In a cell-free apoptosis system, mitochondria spontaneously released cytochrome c, which activated DEVD-specific caspases, leading to fodrin cleavage and apoptotic nuclear morphology. Bcl-2 acted in situ on mitochondria to prevent the release of cytochrome c and thus caspase activation. During apoptosis in intact cells, cytochrome c translocation was similarly blocked by Bcl-2 but not by a caspase inhibitor, zVAD-fmk. In vitro, exogenous cytochrome c bypassed the inhibitory effect of Bcl-2. Cytochrome c release was unaccompanied by changes in mitochondrial membrane potential. Thus, Bcl-2 acts to inhibit cytochrome c translocation, thereby blocking caspase activation and the apoptotic process.


[The production of knowledge on nursing: challenges in the search of recognition in the interdisciplinary field].
It is about a thematic reflection regarding the current panorama of Nursing and the interdisciplinary issue in Health. It aims at reflecting and discussing about the Nursing practice and its production of scientific knowledge, as well as its influence in the relation with other jobs in the health area. For that, the interdisciplinary relations that exist between Nursing and several other health professions are approached. Finally, some suggestions are made for both the Nursing Graduation and Post-graduation courses as well as for the professionals of this field, with the objective of improving the teaching and the professional practices.


The Feedback-related Negativity Codes Components of Abstract Inference during Reward-based Decision-making.
Behavioral control is influenced not only by learning from the choices made and the rewards obtained but also by "what might have happened," that is, inference about unchosen options and their fictive outcomes. Substantial progress has been made in understanding the neural signatures of direct learning from choices that are actually made and their associated rewards via reward prediction errors (RPEs). However, electrophysiological correlates of abstract inference in decision-making are less clear. One seminal theory suggests that the so-called feedback-related negativity (FRN), an ERP peaking 200-300 msec after a feedback stimulus at frontocentral sites of the scalp, codes RPEs. Hitherto, the FRN has been predominantly related to a so-called "model-free" RPE: The difference between the observed outcome and what had been expected. Here, by means of computational modeling of choice behavior, we show that individuals employ abstract, "double-update" inference on the task structure by concurrently tracking values of chosen stimuli (associated with observed outcomes) and unchosen stimuli (linked to fictive outcomes). In a parametric analysis, model-free RPEs as well as their modification because of abstract inference were regressed against single-trial FRN amplitudes. We demonstrate that components related to abstract inference uniquely explain variance in the FRN beyond model-free RPEs. These findings advance our understanding of the FRN and its role in behavioral adaptation. This might further the investigation of disturbed abstract inference, as proposed, for example, for psychiatric disorders, and its underlying neural correlates.


Coupling between GABA(A)-R ligand-binding activity and membrane organization in β-cyclodextrin-treated synaptosomal membranes from bovine brain cortex: new insights from EPR experiments.
Correlations between GABA(A) receptor (GABA(A)-R) activity and molecular organization of synaptosomal membranes (SM) were studied along the protocol for cholesterol (Cho) extraction with β-cyclodextrin (β-CD). The mere pre-incubation (PI) at 37°C accompanying the β-CD treatment was an underlying source of perturbations increasing [(3)H]-FNZ maximal binding (70%) and K (d) (38%), plus a stiffening of SMs' hydrocarbon core region. The latter was inferred from an increased compressibility modulus (K) of SM-derived Langmuir films, a blue-shifted DPH fluorescence emission spectrum and the hysteresis in DPH fluorescence anisotropy (A (DPH)) in SMs submitted to a heating-cooling cycle (4-37-4°C) with A (DPH,heating) < A (DPH,cooling). Compared with PI samples, the β-CD treatment reduced B (max) by 5% which correlated with a 45%-decrement in the relative Cho content of SM, a decrease in K and in the order parameter in the EPR spectrum of a lipid spin probe labeled at C5 (5-SASL), and significantly increased A (TMA-DPH). PI, but not β-CD treatment, could affect the binding affinity. EPR spectra of 5-SASL complexes with β-CD-, SM-partitioned, and free in solution showed that, contrary to what is usually assumed, β-CD is not completely eliminated from the system through centrifugation washings. It was concluded that β-CD treatment involves effects of at least three different types of events affecting membrane organization: (a) effect of PI on membrane annealing, (b) effect of residual β-CD on SM organization, and (c) Cho depletion. Consequently, molecular stiffness increases within the membrane core and decreases near the polar head groups, leading to a net increase in GABA(A)-R density, relative to untreated samples.


'Discovering' chronic illness: using grounded theory.
This paper focuses on using the grounded theory method to study social psychological themes which cut across diverse chronic illnesses. The grounded theory method is presented as a method having both phenomenological and positivistic roots, which leads to confusion and misinterpretations of the method. A social constructionist version and application of grounded theory are introduced after brief overviews of the method and of the debates it has engendered are provided. Next, phases in developing concepts and theoretical frameworks through using the grounded theory approach are discussed. These phases include: (1) developing and refining the research and data collection questions, (2) raising terms to concepts, (3) asking more conceptual questions on a generic level and (4) making further discoveries and clarifying concepts through writing and rewriting. Throughout the discussion, examples and illustrations are derived from two recent papers, 'Disclosing Illness' and 'Struggling for a Self: Identity Levels of the Chronically Ill'. Last, the merits of the method for theoretical development are discussed.


Uniaxial and biaxial structures in the elastic Maier-Saupe model.
We perform statistical mechanics calculations to analyze the global phase diagram of a fully connected version of a Maier-Saupe-Zwanzig lattice model with the inclusion of couplings to an elastic strain field. We point out the presence of uniaxial and biaxial nematic structures, depending on temperature T and on the applied stress σ. Under uniaxial extensive tension, applied stress favors uniaxial orientation, and we obtain a first-order boundary along which there is a coexistence of two uniaxial paranematic phases, and which ends at a simple critical point. Under uniaxial compressive tension, stress favors biaxial orientation; for small values of the coupling parameters, the first-order boundary ends at a tricritical point, beyond which there is a continuous transition between a paranematic and a biaxially ordered structure. For some representative choices of the model parameters, we obtain a number of analytic results, including the location of critical and tricritical points and the line of stability of the biaxial phase.


Pregnancy and laparoscopic surgery.
We reviewed the English literature regarding laparoscopic surgery during pregnancy and found that of 518 reported procedures, the most common was cholecystectomy (45%), followed by adnexal surgery (34%), appendectomy (15%), and other operations (6%). We add six cases to this list; three cholecystectomies, an adnexal procedure, and two for abdominal pain. Thirty-three percent were performed in the first trimester, 56% in the second, and 11% in the third trimester. This review demonstrates a definite trend, indicating that laparoscopy in pregnancy appears to be safe when performed by experienced practitioners. (J Am Assoc Gynecol Laparosc 6(3):347-351, 1999)


Externalities in hospitals and physician adoption of a new surgical technology: an exploratory analysis.
Much recent work on the economics of new technology adoption has investigated the roles of information and externalities. However, studies of technology adoption by physicians have not addressed these issues. This paper examines the adoption by general surgeons of laparoscopic cholecystectomy, a new surgical procedure which was introduced in 1989. The paper addresses the informational and cost externalities which may be generated when the first surgeon in a hospital adopts a new procedure. The findings suggest that access to information about laparoscopic cholecystectomy influenced surgeons' adoption behavior, and that externalities in hospitals may have hastened the diffusion of the procedure.


Memory in a fractional-order cardiomyocyte model alters properties of alternans and spontaneous activity.
Cardiac memory is the dependence of electrical activity on the prior history of one or more system state variables, including transmembrane potential (Vm), ionic current gating, and ion concentrations. While prior work has represented memory either phenomenologically or with biophysical detail, in this study, we consider an intermediate approach of a minimal three-variable cardiomyocyte model, modified with fractional-order dynamics, i.e., a differential equation of order between 0 and 1, to account for history-dependence. Memory is represented via both capacitive memory, due to fractional-order Vm dynamics, that arises due to non-ideal behavior of membrane capacitance; and ionic current gating memory, due to fractional-order gating variable dynamics, that arises due to gating history-dependence. We perform simulations for varying Vm and gating variable fractional-orders and pacing cycle length and measure action potential duration (APD) and incidence of alternans, loss of capture, and spontaneous activity. In the absence of ionic current gating memory, we find that capacitive memory, i.e., decreased Vm fractional-order, typically shortens APD, suppresses alternans, and decreases the minimum cycle length (MCL) for loss of capture. However, in the presence of ionic current gating memory, capacitive memory can prolong APD, promote alternans, and increase MCL. Further, we find that reduced Vm fractional order (typically less than 0.75) can drive phase 4 depolarizations that promote spontaneous activity. Collectively, our results demonstrate that memory reproduced by a fractional-order model can play a role in alternans formation and pacemaking, and in general, can greatly increase the range of electrophysiological characteristics exhibited by a minimal model.


[Use of ultrasound for gastric volume evaluation after ingestion of different volumes of isotonic solution].
The current preoperative fasting guidelines allow fluid intake up to 2hours before surgery. The aim of this study was to evaluate the gastric volume of volunteers after an overnight fast and compare it with the gastric volume 2hours after ingestion of 200 and 500mL of isotonic solution, by means of ultrasound assessment. Eighty volunteers underwent gastric ultrasound at three times: after 8hours of fasting; 2hours after ingestion of 200mL isotonic saline, followed by the first scan; and on another day, 2hours after ingestion of 500mL of the same solution after an overnight fast. The evaluation was quantitative (antrum area and gastric volume, and the ratio of participants' gastric volume/weight) and qualitative (absence or presence of gastric contents on right lateral decubitus and supine positions. A p-value<0.05 was considered significant). There was no difference in quantitative variables at measurement times (p>0.05). Five volunteers (6.25%) had a volume/weight over 1.5mL.kg-1 at fasting and 2hours after ingestion of 200mL and 6 (7.5%) after 500mL. Qualitatively, the presence of gastric fluid occurred in more volunteers after fluid ingestion, especially 500mL (18.7%), although not statistically significant. Ultrasound assessment of gastric volume showed no significant difference, both qualitative and quantitative, 2h after ingestion of 200mL or 500mL of isotonic solution compared to fasting, although gastric fluid content has been identified in more volunteers, especially after ingestion of 500mL isotonic solution.


Lipoprotein metabolism in a rat model of diet-induced adiposity.
Obesity in humans is associated with decreased plasma levels of high density lipoprotein (HDL), but the mechanisms effecting this relationship have not been established. Four treatment groups were used to develop a range of moderate adiposity: rat pups were raised in litters of 4 or 14 and fed from weaning diets of 6 or 24% fat (wt/wt) for 15-17 wk. Lipoproteins from plasma and from a recirculating in situ liver perfusion system were then separated and analyzed, lipoprotein lipase (LPL) activity was assayed in samples of adipose tissue and skeletal muscle and body composition and cholesterol concentrations of various tissues were determined. There was little effect of the diet or litter size treatments on plasma lipids or lipoprotein profiles. Compared to the marked changes in lipid and lipoprotein metabolism that have been observed in severely obese animal models, there was generally little effect of the treatments used to produce this model of moderate diet-induced adiposity. Adiposity was unrelated to plasma total cholesterol and triglycerides. While fatness was positively, although weakly, correlated with plasma levels of several HDL components, including HDL cholesterol, there were no consistent treatment effects on these measures. Plasma HDL levels and adiposity were unrelated to hepatic HDL production or tissue LPL activities. A review of the literature suggests that differences in plasma HDL responses to adiposity in humans and in experimental animals may be due to inherent species differences in lipoprotein metabolism.


Nucleotide interactions with membrane-bound transporter associated with antigen processing proteins.
The transporter associated with antigen processing (TAP) contains two nucleotide-binding domains (NBD) in the TAP1 and TAP2 subunits. When expressed as individual subunits or domains, TAP1 and TAP2 NBD differ markedly in their nucleotide binding properties. We investigated whether the two nucleotide-binding sites of TAP1/TAP2 complexes also differed in their nucleotide binding properties. To facilitate electrophoretic separation of the subunits when in complex, we used TAP complexes in which one of the subunits was expressed as a fluorescent protein fusion construct. In binding experiments at 4 degrees C using the photo-cross-linkable nucleotide analogs 8-azido-[gamma-(32)P]ATP and 8-azido-[alpha-(32)P]ADP, TAP2 was found to have reduced affinity for nucleotides compared with TAP1, when the two proteins were separately expressed. Complex formation with TAP1 enhanced the binding affinity of the TAP2 nucleotide-binding site for both nucleotides. Binding analyses with mutant TAP complexes that are deficient in nucleotide binding at one or both sites provided evidence for the existence of two ATP-binding sites with relatively similar affinities in TAP1/TAP2 complexes. TAP1/TAP2 NBD interactions appear to contribute at least in part to enhanced nucleotide binding at the TAP2 site upon TAP1/TAP2 complex formation. Binding analyses with mutant TAP complexes also demonstrate that the extent of TAP1 labeling is dependent upon the presence of a functional TAP2 nucleotide-binding site.


N -methyl- D -aspartate (NMDA) induced apoptosis in adult rabbit retinas.
Previously we showed that apoptosis is involved in N -methyl- D -aspartate (NMDA) induced excitotoxicity in adult rat retinas. Since rabbits have a higher endogenous level of glutamate in the retina and very different retinal structures, it is not clear if apoptosis is similarly involved in adult rabbit retinas after intravitreal injection of NMDA. In this study, we used ultrastructural features, TdT-mediated biotin-dUTP nick end labeling (TUNEL) and two caspase inhibitors to examine whether apoptosis is involved in NMDA-induced excitotoxicity in adult rabbit retinas. At 18 hr after an intravitreal injection of 400 nmoles NMDA, typical apoptotic features in degenerative cells in the retinal ganglion cell layer (RGCL) and the inner nuclear layer (INL) were noted by electron microscopy. TUNEL positive nuclei were detected in these layers as early as 4 hr showing maximal numbers at 18 hr. At 7 days, significant loss of nuclei from the RGCL was noted at the visual streak, the superior and the inferior retinas. These losses were abolished by simultaneous administration of MK-801 and ameliorated by YVAD, a caspase-1 inhibitor, but not by IETD, a caspase-8 inhibitor. These results indicated that, similar to adult rat retinas, apoptosis is involved in NMDA receptor-mediated excitotoxicity in rabbit retinas and that specific caspases may play important roles.


Immediate occlusal loading of Brånemark System TiUnite implants placed predominantly in soft bone: 4-year results of a prospective clinical study.
Immediate occlusal implant loading has been documented as a viable treatment option for various indications. However, most of the available studies reported on the short-term outcome of this treatment modality. The purpose of this prospective clinical study was to document, on a long-term basis, the outcome of immediate occlusally loaded Brånemark System Mk IV TiUnite (Nobel Biocare AB, Göteborg, Sweden) implants placed to support fixed reconstructions in various regions of the jaws. Thirty-eight patients received a total of 51 fixed prosthetic reconstructions, all of which were connected on the day of implant insertion. Twenty restorations replaced single teeth, 30 were fixed partial dentures, and 1 was a full-arch fixed lower restoration. These prostheses were supported by 102 Brånemark System Mk IV TiUnite implants (38 maxillary and 64 mandibular), the majority of which were placed in posterior regions (88%) and mainly in soft bone (76%). Resonance frequency measurements and marginal periimplant soft tissue evaluations were conducted during the course of the study. Furthermore, radiographic examinations were performed at the time of prosthesis delivery and at the 1- and 6-month and 1-, 2-, 3-, and 4-year follow-up visits. This report summarizes the results after 4 years of loading. Three maxillary implants were removed, although stable, in one patient at the 8-week follow-up owing to postoperative infection in the adjacent guided bone regeneration area. No implants were lost further on. This resulted in a cumulative implant success rate of 97.1% after 4 years of prosthetic loading. The mean marginal bone remodeling after 4 years of function was 1.3 +/- SD 0.9 mm. At 4 years, absence of marginal plaque and bleeding on probing was reported for 87% and 69% of the sites, respectively, thereby remaining unchanged since the 1-year follow-up. On average, the interproximal soft tissue fill increased for both mesial and distal papillae from scores of 1.4 +/- 1.1 and 1.0 +/- 1.1, respectively, at the preoperative assessment to 2.0 +/- 0.8 and 1.7 +/- 0.8, respectively, at the 4-year assessment. The applied immediate loading protocol, in combination with a slightly tapered implant design and a modified implant surface texture, was shown to be a successful treatment alternative in regions exhibiting soft bone.


[Alkoxyl lipids--relics of the organic world: their formation, biotransformation and evolution].
The data on discovery, biosynthesis and distribution of alcoxylipids in different kingdoms of the organic world, their physiologic role and biologic action are given. A conception of possible abiotic synthesis of alcoxylipids on the early stages of the Earth evolution and the ways of their biotransformation is considered. The first biologic membranes are suggested to contain primarily alcoxylipids. During the appearing of photosynthetic mechanism and its improving the alcoxylipids of biomembranes oxidized in plasmalogens and then into diacyl lipids. The possibilities to use alcoxylipids as chemical makers of biomembranes for chemotaxonomy are under discussion.


Microdissection and chromosome painting of X and B chromosomes in Locusta migratoria.
Acquisition of knowledge of the nature and DNA content of B chromosomes has been triggered by a collection of molecular techniques, one of which, microdissection, has provided interesting results in a number of B chromosome systems. Here we provide the first data on the molecular composition of B chromosomes in Locusta migratoria, after microdissection of the B and X chromosomes, DNA amplification by one (B) or two (X) different methods, and chromosome painting. The results showed that B chromosomes share at least two types of repetitive DNA sequences with the A chromosomes, suggesting that Bs in this species most likely arose intraspecifically. One of these repetitive DNAs is located on the heterochromatic distal half of the B chromosome and in the pericentromeric regions of about half of the A chromosomes, including the X. The other type of repetitive DNA is located interspersedly over the non-centromeric euchromatic regions of all A chromosomes and in an interstitial part of the proximal euchromatic half of the B chromosome. Chromosome painting, however, did not provide results sufficiently reliable to determine, in this species, which A chromosome gave rise to the B; this might be done by detailed analysis of the microdissected DNA sequences.


[Familial amyotrophic lateral sclerosis with rapid progression].
We report a family with autosomal dominant (AD) motor neuron disease. A 41-year-old man developed muscle weakness and fasciculation of the lower extremities. The weakness progressed to the upper extremities and bulbar muscles. The cerebrospinal fluid (CSF) protein level was slightly elevated. A nerve conduction study revealed reduced compound muscle action potentials, but conduction block was not observed. Electromyogram showed acute and chronic neurogenic changes. He was treated with intravenous immunoglobulin (IVIg) and methylprednisolone pulse therapy, but his condition rapidly deteriorated. He developed respiratory failure necessitating artificial ventilation within three months after the onset of the disease. His father developed muscle weakness and atrophy of the upper extremities at age 70, and his cousin developed muscle weakness of the legs at age 41. Their conditions rapidly progressed to quadriplegia. CSF and electrophysiological findings were similar to those of the proband. Treatments by steroid pulse therapy, IVIg, and plasmapheresis were not effective. The father and cousin also required artificial ventilation within 3-4 months from the onset of symptoms, and became locked-in state. Autosomal dominant amyotrophic lateral sclerosis (AD-ALS) was considered, but SOD1 gene mutation was not detected. The present pedigree may have familial ALS caused by a gene mutation other than SOD1.


Implementation of tunneled versus not tunneled peripherally inserted central catheters.
Tunneled peripherally inserted central catheters (PICCs) offer several advantages such as an exit site at the green zone no matter where the puncture point is and a long subcutaneous route, which is considered a shield against infections and provides comfort to the patient. Clinicians could choose the proper exact exit site so as to avoid blood leakage from the exit point. The aim of the study was to assess the value of the tunneled PICCs versus normal PICCs with no long subcutaneous route. Sixty patients were randomly divided into two groups and underwent a PICC placement procedure between August 2014 and November 2014 and were then observed until February 2015. Thirty of them (group A) underwent a PICC placement procedure, after proper ultrasound scan and under local anesthesia, of the veins of the upper limb, internal jugular and axillary veins. The mean (±standard deviation) age of patients was 54.8 ± 9.2 years (range, 18-80 years). The primary success rate was 100% for all patients in both the groups. The procedure was not painful for the patients. In group A, after 3 months of surveillance, 7 devices were removed because the patients' therapy came to an end, and only in one incident, the catheter was removed due to soft tissue infection. Tunneled PICCs seem to be a safe option and an easy alternative to perform in contrast to placement without a tunnel. It is an easy, cheap procedure that allows us to catheterize the vein with a larger caliber and create an exit point at any preselected point on the upper limb.


Autonomic effects of nebivolol versus atenolol in healthy subjects.
Nitric oxide may stimulate sympathoinhibitory reflexes. Nebivolol is a beta(1) selective adrenergic receptor antagonist with ancillary vasodilating properties by modulating nitric oxide secretion. We investigated whether nebivolol affects autonomic function differently compared with atenolol, another selective beta(1)-blocker without vasorelaxant actions. Fourteen healthy volunteers (9 men, 5 women; 25 +/- 3.7 years) received single oral doses of 5 mg nebivolol, 50 mg atenolol, and 100 mg atenolol, each taken for a 2-week period. Heart rate variability (HRV) measurements in time- (SDNN; rMSSD; pNN50) and frequency-domain (low frequency-LF; high frequency-HF; LF/HF ratio) were used to study the autonomic effects of the three regimens on the same patients from serial 24-hour ECGs. Both nebivolol and atenolol, the 50 mg dose as well as the 100 mg dose, produced similar decreases in heart rate compared with baseline throughout the 24-h period (from 82 +/- 9 beats/min to 72 +/- 7 beats/min, 69 +/- 9, and 68 +/- 8 beats/min, respectively, p < 0.001). Overall, the administration of each beta -blocker led to directionally similar increases in the HRV variables, which were most significant following 100 mg atenolol. Nebivolol and the 50 mg dose of atenolol produced similar increases in rMSSD and pNN50 during the entire 24-h period, and in HF power, particularly during the nighttime (p < 0.05). However, the coefficient of HF variance resulted in similar values after either beta -blocker regimen. The LF/HF ratio was most reduced throughout the 24-h period following 100 mg atenolol (p < 0.001), and to a similar extent decreased in the nighttime following nebivolol and atenolol 50 mg (p < 0.01). Nebivolol 5 mg exerts similar effects on time and frequency domain indexes of HRV as 50 mg atenolol. Nebivolol attenuates sympathetic tone, but does not appear to promote vagal activity more than atenolol.


Immunoglobulin A nephropathy in China: progress and challenges.
IgA nephropathy (IgAN) is the most common primary glomerulonephritis in China. In about 20% of patients it will lead to renal insufficiency within 10 years, even in those with clinically early IgAN, which causes a great burden for patients and society. We reviewed basic and clinical research work in China. Comparisons between data from China and those from other countries were made. The genetic variations conferring susceptibility to IgAN and disease progression as well as the pathogenic role of polymeric IgA1 were investigated in Chinese patients. Clinical features of Chinese IgAN with isolated microscopic hematuria, malignant hypertension, crescentic glomerulonephritis, intrarenal arterial and tubulointerstitial lesions have been characterized. Clinical trials showed that the combined therapy with urokinase + ACEI, or steroid + ACEI was more effective than with ACEI alone in reducing proteinuria and protecting renal function. The therapeutic role of MMF in IgAN remains debated, although two Chinese studies demonstrated its efficacy. Severe pneumonia can possibly occur in some cases after MMF administration for 3 months. IgAN remains a great challenge to Chinese nephrologists. In-depth basic studies and multicenter clinical trials are needed in the future.


A model system for studying metastasis using the embryonic chick.
An assay capable of recovering individual viable rodent cells localized in various organs of the chick embryo is described. This assay is based on the differential sensitivity of chick and rodent cells to the cytotoxic drug ouabain. Utilizing this assay, the potential of the chick embryo as a model system for studying metastasis was examined. Several cell lines were characterized in three ways: (a) ability to form local tumors after cell application onto the chorioallantoic membrane; (b) ability to form macro- or microscopic metastasis in the embryo from chorioallantoic membrane tumors; (c) experimental metastatic ability following i.v. injection into chorioallantoic membrane veins. These results were compared with the results obtained from the ouabain-plating assay. We conclude that this assay permits detection of viable metastatic cells even when tumors cannot be detected and helps to overcome the time constraints that have, in the past, limited the usefulness of the chick embryo in modeling metastasis.


Ultrastructure of the capillary pericytes and the expression of smooth muscle alpha-actin and desmin in the snake infrared sensory organs.
The infrared sensory membranes of pit organs of pit vipers have an extremely rich capillary vasculature that forms many vascular loops, each serving a small number of infrared nerve terminals. We clarified the ultrastructure of capillary pericytes in the pit membranes by scanning and transmission electron microscopy, and examined the immunoreactivity in their cytoplasm to two contractile proteins: smooth muscle alpha-actin (SM alpha-actin) and desmin. The capillary pericytes had two major cytoplasmic processes: thickened primary processes that radiate to embrace the endothelial tube and flattened secondary processes that are distributed widely on the endothelium. Coexpression of SM alpha-actin and desmin was observed in the pericytes of entire capillary segments, and SM alpha-actin was characterized by prominent filament bundles directed mainly at right angles to the capillary long axis. This expression pattern was different from that of capillary pericytes of the scales, where SM alpha-actin was expressed diffusely in the cytoplasm. In a series of electron microscopic sections, we often observed the pericyte processes depressing the endothelial wall. We also observed a close relationship of the pericytes with inter-endothelial cell junctions, and pericyte processes connected with the endothelial cells via gap junctions. From these findings, we surmised that capillary pericytes in the pit membrane have a close functional relationship with the endothelium, and through their contractile and relaxing activity regulate capillary bloodflow to stabilize production of infrared nerve impulses.


Water and nonelectrolyte permeability of isolated rat hepatocytes.
We have measured the diffusive permeability coefficients of isolated rat hepatocytes to 3H2O, [14C]urea, [14C]erythritol, [14C]mannitol, [3H]sucrose, and [3H]inulin, employing a technique previously developed for erythrocytes (Redwood et al., J. Gen. Physiol 64:706-729, 1974). Diffusion coefficients for the tracer molecules were measured in packed hepatocytes, supernatant fluid, and intracellular medium (lysed hepatocytes) and were calculated assuming one-dimensional semi-infinite diffusion through a homogeneous medium. By applying the series-parallel pathway model, the following permeability coefficients (10(-5) cm/sec) for the hepatocyte plasma membrane were obtained. 3H2O, 98.6 +/- 18.4; [14C]urea, 18.2 +/- 5.3; [14C]erythritol, 4.8 +/- 1.6; [14C]mannitol, 3.1 +/- 1.4; [3H]sucrose, 0; [3H]inulin, 0. These results indicate that isolated rat hepatocytes are highly permeable to water and polar nonelectrolytes, when compared with other transporting epithelia. This relatively high cellular permeability is consistent with a model in which nonelectrolyte permeation is via an aqueous pathway of equivalent pore diameter of 8-12 A. The finding that [14C]erythritol and [14C]mannitol cross the hepatocyte plasma membrane indicates that these molecules enter the bile canaliculus through the transcellular route. Conversely, the failure of [3H]sucrose and [3H]inulin to permeate the hepatocyte in the isolated condition supports the concept that biliary entry of these large carbohydrates, at least that fraction which cannot be accounted for by a vesicular mechanism, must occur via the transjunctional shunt pathway.


The scientific platform and activity of the Ukrainian INEC Section.
The Ukrainian INEC Section is the most recently established chapter of the European Institute of Ecology and Cancer (INEC). We herewith review its organization and goals, membership, scientific platform, and areas of scientific activity.


Clinical cardiovascular magnetic resonance imaging.
Magnetic resonance imaging (MRI) is a powerful tool providing high-resolution images of the heart and great vessels without the use of ionizing radiation or contrast agents. MRI systems currently in use at many hospitals can be used effectively in the routine, clinical evaluation of many forms of cardiovascular disease, including great vessel disease, ischemic cardiac disease and congenital cardiac disease. Moreover, quantitative and cine MRI techniques are now available, which provide highly accurate measures of chamber size, wall motion and wall thickening. Recent developments in the areas of myocardial tagging, high-speed imaging and MR assessments of flow and perfusion suggest potential for an increasing role of MRI in the clinical evaluation of the cardiovascular system.


The periaqueductal gray: a prerequisite for ACTH-induced excessive grooming.
The periaqueductal gray is known to be involved in the expression of a variety of behaviours such as aggression, beta-endorphin-induced immobility and peptide-induced excessive grooming. In order to establish whether the periaqueductal gray (PAG) is indispensible for peptide-induced excessive grooming, lesions were placed in the dorsal part of this structure. Subsequently, the grooming-inducing abilities of adrenocorticotropin (ACTH), beta-endorphin and bombesin were tested. The lesioned animals did not display excessive grooming after intracerebroventricular injection of ACTH. beta-Endorphin administration into the lesioned animals resulted in an extreme display of immobility. Local injection of bombesin into the PAG resulted in reduced scratching behaviour followed by immobility. It was hypothesized that excessive grooming (elicited by ACTH) may be mediated through a non-opioid primary target site-situated in the lesioned region of the PAG-while excessive scratching and immobility (elicited by bombesin or beta-endorphin, respectively) may be mediated through an opioid primary target site (situated in the remaining part of the PAG). Furthermore, the analysis of social behaviour of lesioned animals revealed that these animals reacted towards an unfamiliar partner predominantly with freezing behaviour. The increase of beta-endorphin-induced immobility and socially induced freezing (which is morphologically very similar to beta-endorphin-induced immobility) in lesioned animals supports the hypothesis that the release of opioid peptides such as beta-endorphin in the PAG plays a role in the regulation of social behaviour.


Utilizing DNA mutations to trace epithelial cell lineages in human tissues.
Epithelial stem cells are typically multipotential and are likely the cell of origin of epithelial cancers. Tracing the expansion of a single stem cell's progeny, identifying and characterizing these cells in human tissue has proven difficult. Invasive labeling studies, which have led to much success in model organisms, are impracticable in humans. Instead, human studies must rely upon naturally occurring clonal markers: typically somatic DNA alterations that uniquely identify a population of cells with the same ancestry. In normal epithelium, nonpathogenic mitochondrial DNA mutations have proven useful. In premalignant and malignant disease, genomic DNA mutations within tumor suppressor genes or oncogenes can be used to trace the spread of mutant clones.