Insulin glulisine, a new rapid-acting insulin analogue, displays a rapid time-action profile in obese non-diabetic subjects.
This study compared the pharmacokinetics and pharmacodynamics of insulin glulisine, insulin lispro, and regular human insulin in obese subjects. In this single-dose, randomized, double-blind, crossover euglycaemic clamp study, 18 non-diabetic subjects (mean body mass index [BMI] 34.7 kg . m (-2)) were randomized to receive subcutaneous injections of each insulin (0.3 U . kg (-1)) in pre-determined sequences. Insulin glulisine and insulin lispro had more rapid-acting profiles than regular human insulin. Fractional glucose infusion rate (GIR)-area under curves (AUC) of the GIR curve and maximum GIR were greater for insulin glulisine and insulin lispro versus regular human insulin. Total glucose disposal was slightly greater with insulin glulisine than with regular human insulin, and was comparable to insulin lispro, although it decreased with increasing insulin resistance (HOMA index) with all insulins. Time to 20 % (early glucose disposal) and 80 % (bulk of activity) of total GIR-AUC were shorter for insulin glulisine and insulin lispro versus regular human insulin. This was corroborated by more rapid and shorter residing pharmacokinetic profiles of insulin glulisine and insulin lispro versus regular human insulin, evidenced by shorter times to 20 % of total INS-AUC, INS-C (max) (INS-t (max)), and mean residence time. Moreover, time to 20 % of total GIR-AUC demonstrated a less rapid-acting profile for insulin lispro versus insulin glulisine, which was consistent with the slightly less rapid pharmacokinetic profile of insulin lispro. There was no significant correlation between BMI or subcutaneous fat thickness and pharmacokinetic or pharmacodynamic profiles for insulin glulisine, unlike insulin lispro and regular human insulin. Insulin glulisine and insulin lispro demonstrated substantially more rapid time-action profiles than regular human insulin in obese non-diabetic subjects, which prevailed with insulin glulisine irrespective of BMI and subcutaneous fat thickness.


FGFR2 genomic aberrations: Achilles heel in the management of advanced cholangiocarcinoma.
Cholangiocarcinoma is the most common aggressive biliary tract malignancy with dismal prognosis. Though surgical resection of the primary tumors yields better prognosis, majority of patients present at advanced, inoperable stages rendering systemic therapy as the only option. A significant progress has been made in understanding the cholangiocarcinoma tumorigenesis and molecular markers over the last decade, which opens doors to precision medicine in this dismal cancer. Intrahepatic cholangiocarcinomas are most likely to harbor mutations in isocitrate dehydrogenase genes (IDH1, IDH2), fibroblast growth factor receptors (FGFR1, FGFR2, FGFR3), Eph receptor 2 (EPHA2), and BAP1 (gene involved in chromatin remodeling) genes, whereas ARID1B, ELF3, PBRM1, cAMP dependent protein kinase (PRKACA, and PRKACB) genetic mutations were implicated more commonly in distal and perihilar subtypes. Genomic studies have shown that FGFR2 aberrations are implicated in approximately 15% of intrahepatic cholangiocarcinomas, which make FGFR2 aberrations (Achilles heel) as potential novel targets in the management of cholangiocarcinoma. The current review comprehensively focuses on the role of FGFR2 inhibition either alone or in combination with other targeted therapy that act on down-stream and alternate kinase pathways in cholangiocarcinoma.


Discovery of highly potent V600E-B-RAF kinase inhibitors: Molecular modeling study.
A series of 20 triarylpyrazole derivatives containing amide or urea linker have been synthesized. Their in vitro antiproliferative activity against NCI-60 cancer cell lines panel has been reported. Upon investigating the mechanism of action at molecular level, compound 1e showed selectivity and potency against V600E-B-RAF (IC50 = 390 nM). Herein, we decided to investigate the potency of the other nineteen target compounds against V600E-B-RAF. This led to discovery of several more potent compounds against that kinase. The IC50 values of compounds 1g-i and 2f-i were within the range of 7-47 nM. Among them, the diarylurea compound 1i was the most potent (IC50 = 7 nM). Results of docking and molecular dynamic analysis suggested the presence of consistent binding mode among our compound series with type-IIA class of inhibition pattern. Subsequently, the contribution of structural features to bioactivity were explored by means of QSAR analysis, where such effort led to the development of predictive QSAR model with significant statistical parameters (R2 = 0.912, F = 38.64, Q2LOO = 0.834, Q2LMO = 0.816, s = 0.334). Furthermore, pharmacophoric features existed among our compound series were investigated employing molecular interaction field (MIF) analysis, which led to the development of partial least squares model consisted of four latent variables (4LV-PLS) with statistical parameters of (R2acc. = 0.98, Q2acc. = 0.81).


Exosomes Derived From T Regulatory Cells Suppress CD8+ Cytotoxic T Lymphocyte Proliferation and Prolong Liver Allograft Survival.
BACKGROUND CD8+ cytotoxic T lymphocytes (CTLs) have been proved to exert crucial roles in immunological rejection. Exosomes (EXOs) secreted by CD4+CD25+ regulatory T (Treg) cells is believed to be deeply involved in immune regulation. Nevertheless, whether immunomodulatory effect of CD4+CD25+ Treg cells on CD8+ CTL depends on EXOs remains unknown and needs to be explored. MATERIAL AND METHODS We purified CD4+CD25+ Treg cells followed by in vitro amplification. EXOs in culture supernatants of Treg cells was separated and identified. The effect of CD4+CD25+ Treg cells and CD4+CD25+ Treg cells-derived EXOs on CD8+ CTL viability, proliferation, cell cycle mRNA, intracellular cytokines, and protein expression were investigated. RESULTS We successfully obtained EXOs from CD4+CD25+ Treg cells. The inhibition effect of EXOs on CD8+ CTL was concentration-dependent. In addition, the inhibition effect of CD4+CD25+ Treg cells could be reversed by GW4869, an EXOs inhibitor. The inhibition effect was associated with the regulation of IFN-γ and perforin. Our in vivo experiments proved that natural CD4+CD25+ Treg cells-released EXOs can prolong liver allograft survival. CONCLUSIONS CD4+CD25+ Treg cells-derived EXOs could become an alternative tool for manipulating the immune system to discover novel underlying immunomodulatory mechanisms.


Minimizing axon bundle activation of retinal ganglion cells with oriented rectangular electrodes.
Retinal prostheses aim to restore vision in patients with retinal degenerative diseases, such as age-related macular degeneration and retinitis pigmentosa. By implanting an array of microelectrodes, such a device creates percepts in patients through electrical stimulation of surviving retinal neurons. A challenge for retinal prostheses when trying to return high quality vision is the unintended activation of retinal ganglion cells through the stimulation of passing axon bundles, which leads to patients reporting large, elongated patches of light instead of focal spots. In this work, we used calcium imaging to record the responses of retinal ganglion cells to electrical stimulation in explanted retina using rectangular electrodes placed with different orientations relative to the axon bundles. We showed that narrow, rectangular electrodes oriented parallel to the axon bundles can achieve focal stimulation. To further improve the strategy, we studied the impact of different stimulation waveforms and electrode configurations. We found the selectivity for focal stimulation to be higher when using short (33 μs), anodic-first biphasic pulses, with long electrode lengths and at least 50 μm electrode-to-retinal separation. Focal stimulation was, in fact, less selective when the electrodes made direct contact with the retinal surface due to unwanted preferential stimulation of the proximal axon bundles. When employed in retinal prostheses, the proposed stimulation strategy is expected to provide improved quality of vision to the blind.


How the menstrual cycle and menstruation affect sporting performance: experiences and perceptions of elite female rugby players.
To explore athletes' past and current experiences and perceptions of the menstrual cycle in relation to its impact on sporting performance. 15 international female rugby players participated in individual semi-structured interviews (age: 24.5±6.2 years). All interviews were recorded and transcribed verbatim, resulting in 37 376 words of text for descriptive and thematic analysis. Inter-rater reliability checks resulted in a concordance of agreement of 83%. Almost all athletes (93%) reported menstrual cycle-related symptoms. Thirty-three per cent perceived heavy menstrual bleeding and 67% considered these symptoms impaired their performances. Two-thirds of athletes self-medicated to alleviate symptoms. Thematic analysis generated 262 meaning units, 38 themes, 10 categories and 4 general dimensions. The four general dimensions were: (1) symptoms: physiological and psychological menstrual cycle-related symptoms such as dysmenorrhoea, flooding, reduced energy levels, worry, distraction, fluctuating emotions and reduced motivation; (2) impact: perceived impact of menstruation on different aspects of daily lives and performance including negative and neutral responses; (3) resolution: the methods/approaches in dealing with menstruation-related concerns including accepting, or adapting and managing symptoms with self-medication or expert treatment; (4) support: available support and comfortability in discussing menstrual cycle-related issues. This study provides the first in-depth insight into athlete's experiences of the menstrual cycle and perceived impact on training and competition. It highlights individual responses to menstrual 'issues' and emphasises the need for clinicians and support staff to undertake menstrual cycle profiling, monitoring and continue to develop awareness, openness, knowledge and understanding of the menstrual cycle.


The Impact of Internal Migration on the Maternal and Child Health Services Utilization in Turkey.
This study aims to determine the effect of internal migration and various socio-demographic and socio-economic factors on maternal and child health services utilization in Turkey. In this context, prenatal care, giving birth at health-care facilities, and postnatal care have been examined. The data of Turkey Demographic and Health Survey were used in the study. The best conditions for maternal and child health services utilization were those who lived in urban, then, respectively, those who were rural to urban migrants, urban to rural migrants, and rural women. Rural people constituted the most disadvantaged group in terms of health-care utilization.


Developmental neurotoxicity of ketamine: morphometric confirmation, exposure parameters, and multiple fluorescent labeling of apoptotic neurons.
Ketamine is a widely used pediatric anesthetic recently reported (C. Ikonomidou et al., 1999, Science 283, 70-74) to enhance neuronal death in neonatal rats. To confirm and extend these results, we treated four groups of PND 7 rats with seven sc doses, one every 90 min, of either saline, 10 mg/kg ketamine, 20 mg/kg ketamine, or a single dose of 20 mg/kg ketamine. The repeated doses of 20 mg/kg ketamine increased the number of silver-positive (degenerating) neurons in the dorsolateral thalamus to a degree comparable to previous results (Ikonomidou et al., 1999, Science 283, 70-74), i.e., 28-fold vs. 31-fold respectively. However, blood levels of ketamine immediately after the repeated 20 mg/kg doses were about 14 micrograms/ml, about seven-fold greater than anesthetic blood levels in humans (J. M. Malinovsky et al., 1996, Br. J. Anaesth. 77, 203-207; R. A. Mueller and R. Hunt, 1998, Pharmacol. Biochem. Behav. 60, 15-22). Levels of ketamine in blood following exposure to the multiple 10 mg/kg doses of ketamine or to a single 20 mg/kg dose ranged around 2-5 micrograms/ml; although these blood levels are close to an anesthetic level in humans, they failed to produce neurodegeneration. To investigate the mode of ketamine-induced neuronal death, coronal sections were stained with both Fluoro-Jade B (a green fluorescent stain selective for neurodegeneration) and DAPI (a blue DNA stain), as well as for caspase-3 (using an antisera labeled red with rhodamine). These histochemical results confirmed the developmental neurotoxicity of ketamine, demonstrated that Fluoro-Jade B (FJ-B), like silver methods, successfully stained degenerating neurons in neonatal rats, and indicated that ketamine acts by increasing the rate of neuronal apoptosis.


Gastrointestinal involvement in tuberous sclerosis. Two case reports.
Two patients with tuberous sclerosis had multiple semispherical polyps in the large intestine, predominantly in the rectosigmoid colon. These were hamartomas with an excess of smooth muscle fibers in the stroma. In addition, the 21-year-old man had multiple tiny protrusions in the esophagus and oral fibroepithelial polyps. In the 31-year-old woman, who had pulmonary lymphangiomyomatosis with positive estrogen and progesterone receptors, hamartomatous gastric polyps, colonic leiomyoma, and adenomatous rectal polyps were also identified. Our findings suggest that gastrointestinal polyposis may be one of the phenotypes of tuberous sclerosis complex, possibly linking this disease with other hereditary polyposis syndromes.


Water-saving analysis on an effective water reuse system in biodiesel feedstock production based on Chlorella zofingiensis fed-batch cultivation.
The micralgae-based biofuel obtained from dairy wastewater (DWW) is considered a promising source of energy. However, this process consumes water due to the concentration of wastewater being normally too high for some micoralgae cultivation, and dilution is always needed. In this work, the cultivation of microalgae has been examined in non-recirculated water (NR) and recirculated water systems (R). The growth of Chlorella zofingiensis and the nutrient removal of DWW have been recorded. The comparison indicates the R had a little more advantage in biomass and lipid output (1.55, 0.22 g, respectively) than the NR (1.51, 0.20 g, respectively). However, the total chemical oxygen demand (COD), total Kjeldahl nitrogen (TKN), and total phosphorus (TP) removals of the R were lower than those of the NR system during the culture. The highest removal of total COD, TKN, and TP were 85.05%, 93.64%, and 98.45%, respectively. Furthermore, no significant difference has been observed in the higher heating value and lipid content of the biomass of the R and NR. The results show the R can save 30% of the total water input during the culture. All above results indicate the R system has great potential in industry.


Secondary uncommon solid neoplasms in cured Hodgkin's disease and follow-up of the original B-DOPA chemotherapy patient group.
Three patients with Stage III or IVB Hodgkin's disease were cured with MOPP (regimen of nitrogen mustard, Oncovin, prednisone, and procarbazine) and/or B-DOPA (regimen of bleomycin, dacarbazine, Oncovin, prednisone, and Adriamycin). One had also received prior mantle radiation. After 13, 15 and 18 years in complete remission, three unusual solid tumors were diagnosed. One patient presented with a T3N2M0 epidermoid carcinoma of the soft palate; the second patient developed a T2N1M0 epidermoid carcinoma of the anus. The third patient developed a meningeal sarcoma that was metastatic to the lungs. Two additional patients, both of whom received MOPP and B-DOPA, died with more common tumors (esophageal and renal cell) at 7 and 10 years in association with recurrent Hodgkin's disease. Uncommon tumors may develop after long intervals following treatment for Hodgkin's disease and early detection requires diligent and persistent follow-up. The retrospective review of long-term survivors of the original B-DOPA regimen is of particular interest in that four of seven such patients developed solid tumors at 7, 10, 13, and 15 years. These patients had all received MOPP chemotherapy and six of seven had received radiation as well. The possibility of delayed solid tumors developing, particularly in patients having received both MOPP and B-DOPA or the related ABVD (regimen of Adriamycin, bleomycin, vinblastine, and dacarbazine) program, is of some concern.


Pellagra encephalopathy following B-complex vitamin treatment without niacin.
Pellagra is caused by nicotinic acid deficiency; it is rarely encountered in developed countries, and it is mainly related to poverty and malnutrition, as well as with chronic alcoholism. We report the case of an alcoholic patient who was diagnosed with pellagra and administered B-complex vitamin tablets that did not contain niacin. A few weeks later, the patient developed nervousness, irritability, insomnia and, consequently, delusional ideas and hallucinations, for which he had to be hospitalized. After his admission, the patient manifested loss of consciousness and myoclonus. All of his symptoms (cutaneous, neurological, and psychiatric) resolved fully with treatment with niacin in combination with other B-complex vitamins. All undiagnosed encephalopathies in alcoholic patients should be treated with multiple vitamin therapy, including nicotinic acid.


The stemness gene expression of cultured human amniotic epithelial cells in serial passages.
The aim of the study is to evaluate the stemness gene expression of cultured human amniotic epithelial cells (HAECs) in serial passages. HAECs obtained from human term placentae were cultured in F12:DMEM(1:1) + 10% FBS +10ng/ml EGF in serial passages (P0, P1, P2 and P4). Quantitative RT-PCR was used to assess the gene expression analysis. The results showed that cultured HAECs expressed and downregulated the stemness genes expression for Oct-4, Sox-2, Nanog3, FGF4, Rex-1, FZD-9, BST-1 ABCG2. However, vimentin and nestin gene expression were upregulated. The results suggested that cultured HAECs may have pluripotent and multipotent properties.


Shared versus specialized glycinergic spinal interneurons in axial motor circuits of larval zebrafish.
The neuronal networks in spinal cord can produce a diverse array of motor behaviors. In aquatic vertebrates such as fishes and tadpoles, these include escape behaviors, swimming across a range of speeds, and struggling. We addressed the question of whether these behaviors are accomplished by a shared set of spinal interneurons activated in different patterns or, instead, involve specialized spinal interneurons that may shape the motor output to produce particular behaviors. We used larval zebrafish because they are capable of several distinct axial motor behaviors using a common periphery and a relatively small set of spinal neurons, easing the task of exploring the extent to which cell types are specialized for particular motor patterns. We performed targeted in vivo whole-cell patch recordings in 3 d post fertilization larvae to reveal the activity pattern of four commissural glycinergic interneuron types during escape, swimming and struggling behaviors. While some neuronal classes were shared among different motor patterns, we found others that were active only during a single one. These specialized neurons had morphological and functional properties consistent with a role in shaping key features of the motor behavior in which they were active. Our results, in combination with other evidence from excitatory interneurons, support the idea that patterns of activity in a core network of shared spinal neurons may be shaped by more specialized interneurons to produce an assortment of motor behaviors.


Alterations in focal adhesion and cytoskeletal proteins during apoptosis.
Ceramide induces cell rounding and subsequent apoptotic cell death in trigeminal neurinoma 476-16 cells. A protein tyrosine phosphatase inhibitor, orthovanadate, inhibits cell rounding and subsequent apoptotic death, while a serine/threonine phosphatase inhibitor, calyculin A, stimulates cell rounding but inhibits apoptosis (reference 11). In an attempt to determine critical cellular changes associated with cell rounding during the induction of apoptosis, focal adhesion and cytoskeletal proteins in apoptotic round cells induced by ceramide were examined by immunoblotting and compared with those of non-apoptotic round cells and adherent cells. As compared with adherent cells, tyrosine phosphorylation of a group of proteins between 110-125 KDa, including p125 focal adhesion kinase (FAK) is reduced in the apoptotic round cells as well as in non-apoptotic round cells induced by calyculin A and metaphase cells in mitosis. However, a concerted decrease of vinculin, paxillin and FAK, preceding the changes of whole cellular proteins, is seen in the apoptotic round cells but not in the non-apoptotic round cells. The inhibition of ceramide-induced apoptosis by orthovanadate is accompanied by a prevention of such a decrease in focal adhesion proteins. It thus appears that these focal adhesion proteins are degraded during the cell rounding occurring during apoptosis. Proteolysis of focal adhesion components may not only irreversibly disrupt cell adhesion but also impede transduction of growth and survival signals, and may play a critical role in the initiation and execution of apoptosis.


[Clinical case of the month: clostridium difficile colitis].
A 55-year-old patient with mant e cels underwent a cytotoxic chemotherapy (D.H.A.P. + Rituximab). During the medullar aplasia related to the third cycle, diarrhoea due to Clostridium difficile arised and relapsed 15 days later despite normal blood counts. This colitis was very severe with pluribacterial peritonitis, but resolved with intensive medical treatment. The incidence, the patient's risk factors, the iatrogenic and nosocomial characters of cl. difficile colitis are discussed.


Mechanisms Involved in the Increased Hemolysis in the Fetus and Newborn.
The suicidal death of erythrocytes should be considered a possible cause of hemolysis and plasma bilirubin overload when there is no evidence of an immune-mediated hemolytic anemia, no consumptive red blood cell disorder, no morphologic or laboratory data to suggest a problem of the red cell membrane, and no evidence of a quantitative or qualitative defect in hemoglobin synthesis. In neonatal period, xenobiotics, cytokines, osmotic shock, energy depletion, oxidative stress, and variation of temperature may induce an alteration of balance between damaging and protecting factors which can be followed by red cell death. The intraerythrocyte redox balance plays a pivotal role in orchestrating the complex molecular mechanisms leading to eryptosis. Neonatal erythrocytes are a target of extracellular free radicals and, at the same time, are themselves generators of free radicals through the Fenton reaction. This review clarifies the complex mechanisms underlying the susceptibility of neonatal erythrocytes to increased oxidative stress.


Dietary magnesium intake and risk of cardiovascular disease among women.
This study assessed the hypothesis that greater magnesium intake is associated with reduced risk for cardiovascular disease (CVD), including myocardial infarction (MI) and stroke, in a large prospective cohort of women. In 1993, a semi-quantitative food frequency questionnaire was used to assess magnesium intake in 39,876 female health professionals aged 39 to 89 years who had no history of CVD or cancer. During a median of 10 years of follow-up, 1,037 incident cases of CVD were identified, including 280 nonfatal MIs and 368 strokes. After adjustment for age and randomized treatment status, magnesium intake was not significantly associated with risk for incident CVD. Comparing the highest quintile of magnesium intake (median 433 mg/day) with the lowest quintile (median 255 mg/day), the relative risks were 0.87 (95% confidence interval [CI] 0.72 to 1.05, p for trend = 0.24) for total CVD, 0.88 (95% CI 0.70 to 1.12, p for trend = 0.34) for coronary heart disease (CHD), 1.03 (95% CI 0.72 to 1.49, p for trend = 0.96) for nonfatal MI, 1.11 (95% CI 0.61 to 2.00, p for trend = 0.95) for CVD death, and 0.87 (95% CI 0.64 to 1.18, p for trend = 0.55) for total stroke. Additional adjustment for other CVD risk factors did not materially change the observed null associations. In conclusion, the results do not support the hypothesis that magnesium intake reduces the development of CHD, although a modest inverse association with stroke cannot be ruled out.


Effects of bucillamine, a new anti-rheumatic drug, on the experimental autoimmune uveitis in rats.
The in vitro and in vivo effects of a new immunomodulating agent, bucillamine, on experimental autoimmune uveitis (EAU) was studied in the rat. The capacity of S-antigen-sensitized lymphocytes to proliferate in response to the antigen or to produce antigen-specific antibodies was significantly suppressed by bucillamine in culture in a dose-dependent manner. The inhibitory effect of bucillamine was significantly enhanced by adding cyclosporin A (CYA) in the culture. The in vivo effects of bucillamine alone or in combination with CYA were further examined in Lewis rats immunized with S-antigen. All untreated rats developed severe EAU 17 days after S-antigen immunization, while rats treated with either bucillamine (200 mg kg-1 day-1) or CYA (2 mg kg-1 day-1) demonstrated milder symptoms of EAU. A combination therapy with bucillamine (20 or 200 mg kg-1 day-1) and CYA (2 mg kg-1 day-1) exhibited much more significant suppression of EAU induction. Although the in vivo treatment with bucillamine or CYA had no effects on the T-cell populations of spleen cells, the combination therapy significantly decreased the CD4+ T-cell population. As for the immune responses to S-antigen in drug-treated rats, bucillamine suppressed the lymphocyte proliferation to S-antigen, which was further suppressed by combination therapy with CYA. The serum antibody levels specific to S-antigen were not affected by tested dose of bucillamine.


Functional and structural characterization of RsbU, a stress signaling protein phosphatase 2C.
RsbU is a positive regulator of the activity of sigmaB, the general stress-response sigma factor of Gram+ microorganisms. The N-terminal domain of this protein has no significant sequence homology with proteins of known function, whereas the C-terminal domain is similar to the catalytic domains of PP2C-type phosphatases. The phosphatase activity of RsbU is stimulated greatly during the response to stress by associating with a kinase, RsbT. This association leads to the induction of sigmaB activity. Here we present data on the activation process and demonstrate in vivo that truncations in the N-terminal region of RsbU are deleterious for the activation of RsbU. This conclusion is supported by comparisons of the phosphatase activities of full-length and a truncated form of RsbU in vitro. Our determination of the crystal structure of the N-terminal domain of RsbU from Bacillus subtilis reveals structural similarities to the regulatory domains from ubiquitous protein phosphatases and a conserved domain of sigma-factors, illuminating the activation processes of phosphatases and the evolution of "partner switching." Finally, the molecular basis of kinase recruitment by the RsbU phosphatase is discussed by comparing RsbU sequences from bacteria that either possess or lack RsbT.


Teaching pain recognition through art: the Ramsay-Caravaggio sedation scale.
Clinical observation is a key component of medical ability, enabling immediate evaluation of the patient's emotional state and contributing to a clinical clue that leads to final decision making. In medical schools, the art of learning to look can be taught using medical humanities and especially visual arts. By presenting a Ramsay sedation score (RSS) integrated with Caravaggio's paintings during a procedural sedation conference for pediatric residents, we want to test the effectiveness of this approach to improve the quality of learning. In this preliminary study, we presented videos showing sedated pediatric patients in the setting of a procedural sedation lesson to two randomized groups of residents, one attending a lesson on RSS explained through the masterpieces of Caravaggio, the other without artistic support. A week later we tested their learning with ten multi-choice questions focused on theoretical questions about sedation monitoring and ten more questions focused on recognizing the appropriate RSS viewing the videos. The primary outcome was the comparison of the total number of RSS layers properly recognized in both groups. We also evaluated the appreciation of the residents of the use of works of art integrated with the lesson. Eleven students were randomized to each group. Two residents in the standard lesson did not attend the test. The percentage of correct answers on the theoretical part was similar, 82% in the art group and 89% in the other (p > 0.05). No difference was found in the video recognition part of the RSS recognition test. Residents exposed to paintings shown great appreciation for the integration of the lesson with the Caravaggio's masterpieces. Adding artwork to a standard medical conference does not improve the performance of student tests, although this approach has been greatly appreciated by residents.


A Wettability Metric for Characterization of Capillary Flow on Textured Superhydrophilic Surfaces.
Surface wettability is typically characterized by measuring the static contact angle of a sessile droplet placed on the surface. For extremely wetting surfaces on which liquid spontaneously spreads into a thin liquid film, the near-zero static contact angle is not amenable to measurement and does not fully describe the wetting behavior. There are unmet needs in microfluidics, boiling heat transfer enhancement, and antifogging applications for a metric to characterize highly wetting (i.e., superhydrophilic) textured surfaces based on their capillary-driven liquid pumping performance, as a supplement to the contact angle for this highly wetting regime. To describe the wetting behavior, the textured surface can be approximated as a thin porous layer through which the liquid spreads. An analytical model is developed for the volumetric flow in this layer, which reveals a single superhydrophilicity metric that captures the wetting behavior for a given liquid. A simple experimental approach is proposed to characterize this metric by measuring the volumetric liquid intake into the surface from a filled capillary tube. This approach is validated by characterizing micropillared superhydrophilic surfaces of known geometry; the predicted and measured wetting behaviors show good agreement. The metric proposed in this study offers a simple approach for accurately characterizing and differentiating highly wetting surfaces based on their liquid pumping ability.


ROADMAP and ORIENTAL Trials: the Re-emergence of J-Curve Ghost?
It still remains unknown whether angiotensin-receptor blockers (ARBs) are cardioprotective in patients with type 2 diabetes. The recent two clinical trials, the ROADMAP and the ORIENT, have suggested that fatal cardiovascular events or cardiovascular deaths were unexpectedly higher in olmesartan group. These results suggest that aggressive blood pressure lowering may cause a higher risk in some high-risk patients, especially in those with preexisting coronary heart disease, indicating a possibility that the J-curve phenomenon may exist in some group of patients.


Regulation of the cholesterol ester cycle of cultured Leydig tumor cells.
The MA-10 Leydig tumor cells take up low-density lipoprotein (LDL) from the medium and store the LDL-derived cholesterol as cholesterol esters that can be subsequently mobilized and used for steroid hormone synthesis. The present studies investigate the mechanisms by which cAMP acutely regulates the cellular content of cholesterol esters. In the absence of cholesterol utilization for steroidogenesis, cAMP stimulates cholesterol ester hydrolysis and ester resynthesis proportionally. The augmentation of ester hydrolysis by cAMP is completely matched by increased activity of the acyl-coenzyme-A:cholesterol acyltransferase and thus does not regulate cellular cholesterol ester concentration per se. The more important action of cAMP is to interrupt the cycle of hydrolysis and ester resynthesis by decreasing cholesterol re-esterification. In cells actively synthesizing steroid hormones, cholesterol reesterification is decreased by 82%. The decrease in cholesterol re-esterification occurs because cAMP directs cholesterol normally destined for re-esterification into steroid synthesis; simply blocking the utilization of cholesterol for steroidogenesis completely prevents net cholesterol ester hydrolysis and increases the cellular rate of cholesterol esterification.


Using consensus bayesian network to model the reactive oxygen species regulatory pathway.
Bayesian network is one of the most successful graph models for representing the reactive oxygen species regulatory pathway. With the increasing number of microarray measurements, it is possible to construct the bayesian network from microarray data directly. Although large numbers of bayesian network learning algorithms have been developed, when applying them to learn bayesian networks from microarray data, the accuracies are low due to that the databases they used to learn bayesian networks contain too few microarray data. In this paper, we propose a consensus bayesian network which is constructed by combining bayesian networks from relevant literatures and bayesian networks learned from microarray data. It would have a higher accuracy than the bayesian networks learned from one database. In the experiment, we validated the bayesian network combination algorithm on several classic machine learning databases and used the consensus bayesian network to model the Escherichia coli's ROS pathway.


Blood lead levels in U.S. workers, 1988-1994.
Limited research has been conducted to measure the association between elevated blood lead levels and sociodemographic factors among U.S. workers in various industries and occupations using population-based survey data. Data from the Third National Health and Nutrition Examination Survey ( n = 10,127) were used to determine the blood lead levels in the U.S. workers. The prevalence of elevated blood lead levels > or = 50 microg/dL was 0.001% (1560) among U.S. workers compared with 0.2% (19,953) workers with elevated lead levels > or = 40 microg/dL. Regression analyses indicated that workers in the repair service industry were correlated with higher blood lead levels than those workers in the construction industry. Although low blood lead levels were found for the entire working population, the results showed that there were still high blood lead levels in certain occupations and industries during 1988 to 1994.


Know Your Movements: Poorer Proprioceptive Accuracy is Associated With Overprotective Avoidance Behavior.
Pain-related avoidance of movements that are actually safe (ie, overprotective behavior) plays a key role in chronic pain disability. Avoidance is reinforced through operant learning: after learning that a certain movement elicits pain, movements that prevent pain are more likely to be performed. Proprioceptive accuracy importantly contributes to motor learning and memory. Interestingly, reduced accuracy has been documented in various chronic pain conditions, prompting the question whether this relates to avoidance becoming excessive. Using robotic arm-reaching movements, we tested the hypothesis that poor proprioceptive accuracy is associated with excessive pain-related avoidance in pain-free participants. Participants first performed a task to assess proprioceptive accuracy, followed by an operant avoidance training during which a pain stimulus was presented when they performed one movement trajectory, but not when they performed another trajectory. During a test phase, movements were no longer restricted to 2 trajectories, but participants were instructed to avoid pain. Unbeknownst to the participants, the pain stimulus was never presented during this phase. Results supported our hypothesis. Furthermore, exploratory analyses indicated a reduction in proprioceptive accuracy after avoidance learning, which was associated with excessive avoidance and higher trait fear of pain. PERSPECTIVE: This study is the first to show that poorer proprioceptive accuracy is associated with excessive pain-related avoidance. This finding is especially relevant for chronic pain conditions, as reduced accuracy has been documented in these populations, and points toward the need for research on training accuracy to tackle excessive avoidance.


A pilot study of the use of oral ivermectin to treat head lice in primary school students in Australia.
Head lice are a common, costly public health problem worldwide. We aimed to determine the feasibility of an ivermectin intervention program. Consenting students in two schools were screened for head lice. Infested students and siblings at one school were offered a head lice fact sheet and two doses of oral ivermectin, 7 days apart. Parents of infested students in the other school were given the same fact sheet and asked to treat the child and siblings using their preferred topical treatment. Seven hundred two of 754 (93.1%) students enrolled in the two schools were screened; 40 (5.3%; 95% CI 3.7-6.9) had head lice; 31 (9.4%; 95% CI 6.1-12.2) in the intervention school and nine (2.5%; 95% CI 1.1-3.8) in the control school. Subsequently 93.6% of children in the intervention school were treated with oral ivermectin. No adverse events were reported. At 6 months the reduction in the head lice infestation rates for the intervention and control schools were 87% and 56%, respectively. This pilot study suggests that school wide screening for head lice and the administration of oral ivermectin is feasible and acceptable. A randomized controlled trial at 20 schools is planned.


Side effects and metabolic effects of converting-enzyme inhibitors.
Side effects of angiotensin converting enzyme (ACE) inhibitors are not common with currently recommended doses. Hypotension, hyperkalemia and renal impairment may occur under special circumstances, and relate directly to blockade of ACE, in particular when pre-treatment renin levels are high. Other adverse effects, once quite common when excessive doses of captopril were prescribed, are now rarely seen. A possible exception is cough. Though not dangerous, cough is not infrequently seen during treatment with ACE inhibitors. Experience with these drugs is insufficient to recommend their use in the hypertension of pregnancy. The "metabolic-profile" with ACE inhibitors appears favourable, since they can increase uric acid excretion and lower plasma urate levels, carbohydrate tolerance is unaltered or improved, and lipid levels are unchanged. Electrolyte and metabolic effects of thiazide diuretics are blunted by addition of an ACE inhibitor.


gas1 mutation extends chronological lifespan via Pmk1 and Sty1 MAPKs in Schizosaccharomyces pombe.
In the longevity research by using yeasts, chronological lifespan is defined as the survival time after entry into stationary phase. Previously, screening for long lived mutants of Schizosaccharomyces pombe was performed to identify the novel factors involved in longevity. From this screening, one long lived mutant called as No.36 was obtained. In this study, we identified the mutation caused in gas1+, which encodes glucanosyltransferase (gas1-287 mutation) is responsible for the longevity of No.36 mutant. Through the analysis of this mutant, we found that cell wall perturbing agent micafungin also extends chronological lifespan in fission yeast. This lifespan extension depended on both Pmk1 and Sty1 MAP kinases, and longevity caused by the gas1-287 mutation also depended on these kinases. In summary, we propose that the gas1-287 mutation causes longevity as the similar mechanism as cell wall stress depending on Pmk1 and Sty1 MAPK pathways.


Influence of colloidal silver nanoparticles on the novel flower-like titanium dioxide oxygen sensor performances.
Titanium dioxide (TiO2-anatase phase) thin films, consisting of agglomerated flower-like nanoparticles, have been synthesized using an ultrasonic spray pyrolysis (USP) method in combination with titanium (IV) oxide acetylacetonate [TiO(acac)2], and methanol at 550 degrees C. These thin films were subsequently thermally treated in air, at 950 degrees C for six hours, and the flower-like particles were transformed into smooth surfaces mainly formed by the TiO2-rutile phase. In order to prepare oxygen sensors of good performance, TiO2 thin films were deposited on interdigitated gold electrodes with contacted alumina substrates. The silver colloidal solution was impregnated on the TiO2 thin film. Since the solvent in which the silver nanoparticles are suspended evaporates at 200 degrees C, the thin films were then annealed at this temperature in air for one hour. The effect of colloidal silver nanoparticles on the response of the thin films TiO2 oxygen sensors has been studied, in a mixture with zero-grade air. The gas-sensing properties of TiO2 sensors in an atmosphere of 10(4) ppm of oxygen were measured between 25 and 500 degrees C. The experimental results obtained with colloidal silver nanoparticles as surface additive show that the sensitivity to an O2 concentration of 100 ppm in zero grade air at 300 degrees C reaches a stationary value of 0.40, and 0.03, for TiO2-anatase and -rutile phase films, respectively. This values are as high as those reported for oxygen sensors prepared by more expensive techniques.


Intraoperative electrocochleography during endolymphatic sac surgery: clinical results.
Thirty-eight patients who underwent endolymphatic shunt surgery with intraoperative electrocochleography were questioned regarding control of symptoms. The average follow-up period was 2 years (range, 7 to 40 months). Sixteen (42%) patients showed improvement in the intraoperative electrocochleography potential, 12 (32%) showed worsening, and 10 (26%) showed no change. Complete or substantial control of dizziness was achieved in 36 (95%) patients, and insignificant control in only 2 (5%) patients. Hearing improvement was noted in 4 (11%) patients, and hearing loss in 13 (34%). No correlation was found between intraoperative electrocochleography improvement and dizziness control. However, three of the four patients who had hearing improvement also had the greatest improvement in intraoperative electrocochleography recording. Intraoperative electrocochleography may help the surgeon more accurately identity the true endolymphatic sac and duct.


Imaging Features of Gastrointestinal Neoplasms Complicating Inflammatory Bowel Diseases.
Inflammatory bowel diseases (IBD) are chronic inflammatory diseases affecting the gastrointestinal (GI) tract. Patients with IBD, besides other non-neoplastic complications, are also at increased risk of GI malignancies such as colorectal cancer, small bowel adenocarcinoma and lymphoma. The principal purpose of imaging in patients with IBD to assess complications and to stage a clinically known cancer. In addition, the goal of imaging has expanded to include the diagnosis of GI malignancies in clinical situations where colonoscopy cannot be performed or is incomplete. In addition, imaging allows the detection of cancers in patients where the development of either disease-related or treatment-related neoplasia is clinically suspected. The purpose of this review is to present the different imaging techniques used to detect GI malignancies in IBD patients and describe the radiological appearances of GI malignancies in IBD patients.


Activated leukocyte cell adhesion molecule is involved in excitatory synaptic transmission and plasticity in the rat spinal dorsal horn.
Activated leukocyte cell adhesion molecule (ALCAM), a member of type I transmembrane immunoglobulin superfamily of cell adhesion molecule, is expressed in the surface membrane of various cell types including neurons. In the spinal cord dorsal horn (DH), the first gate for the sensory and pain transmission to the brain, the expression and function of ALCAM have not been known yet. Therefore, we here investigate the synaptic function of ALCAM in the substantia gelatinosa (lamina II) of the spinal DH, as well as its expression in the DH. Bath-application of ALCAM/Fc or CD6/Fc, the recombinant human IgG1-Fc chimeric proteins, specifically potentiated C-fiber-mediated excitatory synaptic transmission and predominantly increased spontaneous release of glutamate. In addition, the development of long-term potentiation, a form of synaptic plasticity, at excitatory synapses was significantly inhibited in the presence of the recombinant proteins. The functional roles of ALCAM in the spinal DH were further supported by immunohistochemical analysis; it showed that ALCAM intensely expressed through laminae I/II with the exception of lateral portion of the dorsal part of inner lamina II and distinctly co-localized with molecular markers of C-fibers, such as peptidergic calcitonin gene-related protein and transient receptor potential vanilloid type 1 and non-peptidergic isolectin B4. This study, for the first time, suggests the modulatory roles of ALCAM in the excitatory synaptic transmission and plasticity in the rat spinal DH.


Qualities of Sore Throat Index (QuaSTI): measuring descriptors of sore throat in a randomized, placebo-controlled trial.
Patients with pharyngitis often describe various sensory, affective and evaluative pain qualities. Using an 11-word/phrase index, the Qualities of Sore Throat Index (QuaSTI), we characterized throat symptoms and evaluated changes in a randomized controlled trial (NCT01986361). Patients received a single flurbiprofen 8.75 mg (n = 101) or placebo (n = 21) lozenge and rated throat soreness at baseline and regular intervals over 3 h, and the QuaSTI at baseline, 1, 2 and 3 h post-treatment. The QuaSTI distinguished active drug from placebo and detected clinically important (≥2-point) changes over 3 h. Mean change from baseline over 3 h was significantly greater for flurbiprofen (154%) than placebo (p < 0.05). The QuaSTI is a sensitive instrument for measuring therapeutic effects in patients with pharyngitis.


Tumor necrosis factor-alpha and interleukin-1beta levels in recurrent and persistent otitis media with effusion.
Based on interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha levels in effusions, our goals were to specify either recurrent or persistent otitis media with effusion (OME) is a mid stage in the development of chronic disease and to identify the factors that have an influence on cytokine levels. Samples from groups with recurrent (n = 15) and persistent (n = 39) OME were assayed for IL-1beta and TNF-alpha. Children were also grouped with respect to age, sex, quality of effusion, and the presence of pharyngeal adenoid tissue. Tertiary referral center. In recurrent and persistent OME groups, IL-1beta was higher than TNF-alpha (P < 0.01). IL-beta was higher in recurrent OME than in persistent OME (P < 0.05). Recurrent OME seems to be closer to the chronic stage of the disease relative to persistent OME in terms of higher IL-1beta levels. Each exacerbation of acute disease in recurrent otitis media is likely to be mediated by IL-1beta. We were able to clarify that recurrent OME is a stage that occurs before chronic OME. Therefore, the prevention of acute attacks in recurrent disease would also impede long-term damage to the middle ear.


Radiographic Findings in Patients with Medication-Related Osteonecrosis of the Jaw.
A retrospective study was conducted of the records and panoramic radiographs of 35 patients treated with bisphosphonates (BP) and diagnosed with MRONJ. Panoramic radiography was used for evaluation, by two examiners, the following findings were subject of search: osteolysis (OT), cortical bone erosion (EC), bone sclerosis focal (FS) and diffuse (DS), bone sequestration (BS), thickening of lamina dura (TD), prominence of the inferior alveolar nerve canal (IAN), persisting alveolar sockets (SK), and the presence of a pathological fracture (PF). Medical information and staging were also recorded in order to correlate with radiographic findings. Bone sclerosis was the most frequent alteration, followed by OT and TD. The mandible was more affected than the maxilla. There was no significant difference between genders or significant correlation between the number of injuries with age and duration of BP usage. Considering the association between the radiographic findings and MRONJ staging, EC was predominant in stage 3 and DS in stage 2. IAN and PF demonstrated greater association with stage 3. In conclusion, the higher the clinical staging, the greater the severity of the bone alteration. Panoramic radiographic examination is a useful screening tool in patients submitted to antiresorptive therapy.


Backscattered electron imaging of human leukocytes.
Methods of backscattered electron imaging (BEI) have been applied to the study of normal and malignant human leukocytes. Four different elements, principally of high atomic number, have been used: iron, silver, lead and osmium. Iron, in the form of iron carbonyl, has been found to be an excellent marker for the phagocytic activity of granulocytes and monocytes. Silver staining permitted a clear observation of the shape of the nuclei and of the nucleo-cytoplasmic ratio and made the identification of polymorphonuclear cells and of certain normoblasts possible. Lead phosphate precipitates, deposited as a result of a classic acid phosphatase reaction, were detected in several cases of myelocytic and monocytic leukemias. Precipitates of osmium/diaminobenzidine complex on peroxidase-containing granules permitted the unambiguous identification of several classes of myeloid precursors. In all these techniques, the surface morphology of the cells was adequately preserved and could be correlated with the presence and/or the distribution of the various markers.


Atomic-resolution structure of the α-galactosyl binding Lyophyllum decastes lectin reveals a new protein family found in both fungi and plants.
The crystal structure of the α-galactosyl binding Lyophyllum decastes lectin (LDL) was determined to 1.0 Å resolution by sulfur single-wavelength anomalous diffraction (SAD). The 10 kDa protein exhibits no sequence similarity to any protein with known structure and adopts a unique lectin fold, where a core of two antiparallel β-sheets at the heart of the homodimer is connected to the periphery of the structure by intramolecular disulfide bridges. This fold suggests that LDL is secreted, which sets it apart from other mushroom lectins. Structures of complexes between LDL and the ligands α-methylgalactoside and globotriose shed light on the binding specificity. Sequence comparison suggests a location and function of LDL and homologous proteins in or at the fungal cell wall. Structural comparison allows the identification of a superfamily of secreted proteins with the LDL fold, which may play a role at the interface between fungi and their environment.


Diversity of nitrile hydratase and amidase enzyme genes in Rhodococcus erythropolis recovered from geographically distinct habitats.
A molecular screening approach was developed in order to amplify the genomic region that codes for the alpha- and beta-subunits of the nitrile hydratase (NHase) enzyme in rhodococci. Specific PCR primers were designed for the NHase genes from a collection of nitrile-degrading actinomycetes, but amplification was successful only with strains identified as Rhodococcus erythropolis. A hydratase PCR product was also obtained from R. erythropolis DSM 43066(T), which did not grow on nitriles. Southern hybridization of other members of the nitrile-degrading bacterial collection resulted in no positive signals other than those for the R. erythropolis strains used as positive controls. PCR-restriction fragment length polymorphism-single-strand conformational polymorphism (PRS) analysis of the hydratases in the R. erythropolis strains revealed unique patterns that mostly correlated with distinct geographical sites of origin. Representative NHases were sequenced, and they exhibited more than 92.4% similarity to previously described NHases. The phylogenetic analysis and deduced amino acid sequences suggested that the novel R. erythropolis enzymes belonged to the iron-type NHase family. Some different residues in the translated sequences were located near the residues involved in the stabilization of the NHase active site, suggesting that the substitutions could be responsible for the different enzyme activities and substrate specificities observed previously in this group of actinomycetes. A similar molecular screening analysis of the amidase gene was performed, and a correlation between the PRS patterns and the geographical origins identical to the correlation found for the NHase gene was obtained, suggesting that there was coevolution of the two enzymes in R. erythropolis. Our findings indicate that the NHase and amidase genes present in geographically distinct R. erythropolis strains are not globally mixed.


Evolution of tenofovir-resistant HIV-1 isolates exposed to tenofovir alafenamide dose escalation.
Resistance selection experiments using HIV-1 isolates harboring pre-existing tenofovir (TFV)-resistance (K65R, 3TAMs, and Q151M complex) were carried out with the novel tenofovir prodrug tenofovir alafenamide (TAF) as well as with tenofovir (TFV), to investigate the potential for additional resistance development in the presence of TAF or TFV. Extended resistance selection of these TFV resistance associated mutations (RAMs)-containing viruses with TAF or TFV did not lead to the accumulation of additional known RAMs, or significant additional phenotypic resistance, after 6 months in culture. Two new mutations were found during the selections (L429I, T69I) that were further characterized, and found to have very limited or no role in resistance to TAF or TFV. Notably, viral survival in the presence of drug increases could not be sustained and led to viral cure in cell culture, suggesting a lack of alternative resistance pathways for the mutant viruses.


Urinary cytology in endometriosis of the bladder.
A case of endometriosis of the urinary bladder in a 27-year-old black female is reported. The cytologic, histologic and clinical findings are presented, and the differential diagnosis is discussed.


Factors associated with discharge against medical advice in alcohol withdrawal patients.
This study aimed to examine characteristics associated with discharge against medical advice from the hospital in alcohol withdrawal patients, supporting the work of hospital staff and Alcohol Care Teams and identifying characteristics that may help target patients most likely to discharge against medical advice. We used Hospital Episode Statistics Data to identify demographic and clinical variables and compare these in alcohol withdrawal patients who discharged against medical advice from hospital, compared with those who were discharged by the clinical team. Factors significantly associated with alcohol withdrawal patients discharging against medical advice from hospital were: being admitted as an emergency; discharged on a weekend; living with no fixed abode; being male; being younger and having a shorter length of stay. This study identifies characteristics that can be used to support acute hospitals and Alcohol Care Teams, particularly in the allocation of resources to reduce discharges against medical advice and subsequent readmissions to the hospital. Particular consideration should be given to clinical provision in hospitals in emergency departments and on weekends, and also those patients who are admitted and are of no fixed abode.


Neuro-explicit semantic segmentation of the diffusion cloud chamber.
For decades, in diffusion cloud chambers, different types of subatomic particle tracks from radioactive sources or cosmic radiation had to be identified with the naked eye which limited the amount of data that could be processed. In order to allow these classical particle detectors to enter the digital era, we successfully developed a neuro-explicit artificial intelligence model that, given an image from the cloud chamber, automatically annotates most of the particle tracks visible in the image according to the type of particle or process that created it. To achieve this goal, we combined the attention U-Net neural network architecture with methods that model the shape of the detected particle tracks. Our experiments show that the model effectively detects particle tracks and that the neuro-explicit approach decreases the misclassification rate of rare particles by 73% compared with solely using the attention U-Net.


[Carcinoid heart disease and primary ovarian tumor].
Carcinoid heart disease occurs in about one third of patients with carcinoid syndrome, especially in those with ileal carcinoid and hepatic metastases. Patients with primary ovarian carcinoid tumor are extremely rare. In these circumstances, typical carcinoid cardiac lesions may develop unassociated with hepatic metastases, due to the venous drainage from the ovaries into the inferior vena cava of vasoactive released substances such as serotonin. The present report describes a woman with unrecognized primary ovarian carcinoid tumor, unexpectedly exhibiting heart failure. Diagnosis was performed on the basis of echocardiographic findings, occurrence of diarrhea and increased levels of 5-hydroxy-indoleacetic acid (5-HIAA). After complete surgical removal of the tumor, the patient was maintained under therapy with ACE-inhibitors and diuretics. Levels of 5-HIAA are still within normal range, there is regression of heart failure and echocardiographic findings are stabilized. These data confirm the importance of prompt diagnosis for a favorable prognosis of carcinoid heart disease.


Efficacy of Chronic Paroxetine Treatment in Mitigating Amyloid Pathology and Microgliosis in APPSWE/PS1ΔE9 Transgenic Mice.
Modulation of serotonergic signaling by treatment with selective serotonin reuptake inhibitors (SSRIs) has been suggested to mitigate amyloid-β (Aβ) pathology in Alzheimer's disease, in addition to exerting an anti-depressant action. To investigate the efficacy of chronic treatment with the SSRI paroxetine, in mitigating Aβ pathology and Aβ plaque-induced microgliosis in the hippocampus of 18-month-old APPswe/PS1ΔE9 mice. Plaque-bearing APPswe/PS1ΔE9 and wildtype mice were treated with paroxetine per os at a dose of 5 mg/kg/day, from 9 to 18 months of age. The per os treatment was monitored by recording of the body weights and serum paroxetine concentrations, and by assessment of the serotonin transporter occupancy by [3H]DASB-binding in wildtype mice. Additionally, 5,7-dihydroxytryptamine was administered to 9-month-old APPswe/PS1ΔE9 mice, to examine the effect of serotonin depletion on Aβ pathology. Aβ pathology was evaluated by Aβ plaque load estimation and the Aβ42/Aβ40 ratio by ELISA. Paroxetine treatment led to > 80% serotonin transporter occupancy. The treatment increased the body weight of wildtype mice, but not of APPswe/PS1ΔE9 mice. The treatment had no effect on the Aβ plaque load (p = 0.39), the number and size of plaques, or the Aβ plaque-induced increases in microglial numbers in the dentate gyrus. Three months of serotonin depletion did not significantly impact the Aβ plaque load or Aβ42/Aβ40 ratio in APPswe/PS1ΔE9 mice at 12 months. Our results show that chronic treatment with the SSRI paroxetine does not mitigate Aβ pathology and Aβ plaque-induced microgliosis in the hippocampus of APPswe/PS1ΔE9 mice.


[Respiratory mechanics in professional flautists].
Oesophageal, gastric, mouth, transdiaphragmatic, transpulmonary pressures, diaphragmatic EMG, sound and chest wall excursion were measured directly in 3 professional flautists whilst playing their instruments to determine: - what respiratory muscles and percent vital capacity were being used; - how mouth pressure, embouchure resistance, embouchure aperture, airflow and velocity affect sound loudness and frequency. Lung volume was estimated from transpulmonary pressure during playing and the static deflation pressure-volume curve was measured separately; flow was calculated from delta volume/delta time; embouchure resistance was calculated from mouth pressure/flow; velocity was calculated using Bernouilli's equation and mouth pressure. Staccati and sustained tones at different frequency and intensity were performed. Sound loudness was mainly related to airflow whilst sound frequency was determined by velocity. Flow and velocity were independently controlled by mouth pressure and embouchure aperture. Mean mouth pressures varied little from individual to an other (6-11 cm H(2)O) but the flautists used between 72-83% of their vital capacity suggesting inspiratory muscle activity while playing. However, rib cage and abdominal motion were different for each subject. Although different flautists use different strategies to control mouth pressure, their individual mastery of the instrument permits control of airflow and velocity to produce the desired intensity and frequency of sound.


Clinical and social characteristics of the patients with tuberculosis in Eastern Anatolia.
Tuberculosis (TB) is an important public-health problem. The risk factors for TB are well-known. However, there may be some regional differences. In this study, we aimed to investigate the demographic characteristics and regional risk factors for TB and to discuss possible explanations for the difference. The study included totally 253 hospitalized patients (145 male and 108 female, with an average age 38+/-18) with TB (117 pulmonary and 136 extrapulmonary) between 1997 and 2004. Their demographic and clinical characteristics were reviewed. TB frequency was higher among the non-working females in urban area (38.3%). TB was also common in farmers which are male (19.8%). TB frequency was higher in the school persons including students, the teachers and the school officials (14.6%) and in the building workers compared with the other workers. There were a history of previous TB, TB exposure (mostly from family members) and associated disease in 10.3%, 14.2% and 17.4% of cases, respectively. The most encountered associated disease was diabetes. The results indicate that TB was most common among non-working females and was also increased among the men in rural areas, and schools seem to be an important source of TB transmission. Thus, an effective control program covering the treatment of cases with active disease, such as directly observed treatment, and especially preventive measures should be considered to control the disease transmission in our region.


Connectome of the fly visual circuitry.
Recent powerful tools for reconstructing connectomes using electron microscopy (EM) have made outstanding contributions to the field of neuroscience. As a prime example, the detection of visual motion is a classic problem of neural computation, yet our understanding of the exact mechanism has been frustrated by our incomplete knowledge of the relevant neurons and synapses. Recent connectomic studies have successfully identified the concrete neuronal circuit in the fly's visual system that computes the motion signals. This identification was greatly aided by the comprehensiveness of the EM reconstruction. Compared with light microscopy, which gives estimated connections from arbor overlap, EM gives unequivocal connections with precise synaptic counts. This paper reviews the recent study of connectomics in a brain of the fruit fly Drosophila and highlights how connectomes can provide a foundation for understanding the mechanism of neuronal functions by identifying the underlying neural circuits.


Two principles for improving the adaptation of stainless steel crowns to primary molars.
Two principles are discussed that address the length and marginal contours of stainless steel crowns. Application of morphologic findings of teeth and contours of marginal gingival tissues are presented to support these principles. Clinical applications of these principles are discussed. Use of them in your technique will enhance the efficient adaptation of stainless steel crowns. In fact, you will be more efficient with guesswork eliminated. Also, incorporation of the principles into your technique will ensure that the efforts you make will result in the adaptation of custom stainless steel crowns for your patients.


[Short and long-term results of endovascular treatment of bifurcational coronary stenosis].
Short and long-term results of endovascular treatment of true bifurcational coronary stenosis were analyzed in 229 patients. 68 patients received a "provisional-T" stenting on the first stage of the study. On the next stage 40 patients received the same "provisional-T" stenting, a total bifurcational stenting was conducted in 37 patients. Only coated stents were used. Independent risk factors of "provisional-T" stenting conversion to total bifurcational stenting were revealed. There were no differences between "provisional-T" and total bifurcational stenting considering the short-term treatment results. Long-term results (12-18 months) were analyzed in 70 patients. There were no restenosis of the main artery, whereas restenosis of the lateral branch was noticed in 5.5 and 2.94%, respectively, in the groups of "provisional-T" and total bifurcational stenting. Late thrombosis was registered in 1 case from the group of total bifurcational stenting.


Comparative analysis between ultrasonic shears versus advanced bipolar device in transoral endoscopic thyroidectomy: a randomized controlled trial.
The transoral endoscopic thyroidectomy vestibular approach (TOETVA) is the most recently developed minimally invasive technique with no skin incision. For tissue dissection and bleeding control, the use of proper energy devices is very important in endoscopic thyroid surgery. To date, there have been no clinical studies reported regarding which energy device is better in TOETVA, ultrasonic shears or advanced bipolar device. The aim of our study is to determine which energy device is more useful for TOETVA. This study was designed as an open-label, prospective randomized controlled trial in a single university hospital. Patients were randomly assigned to the ultrasonic group or advanced bipolar group before the surgery. From June 2020 to May 2022, 40 patients were enrolled (20 patients were assigned to the ultrasonic group, and 20 patients were assigned to the advanced bipolar group). Primary endpoints were operation time for lobectomy, number of camera cleanings, and blood loss during the lobectomy. Secondary endpoints were pain score, postoperative drainage, and blood chemistry. A single endocrine surgeon had performed all surgeries. There were no significant differences between the two groups in age, sex, body mass index (BMI), tumor location, preoperative cytology, or surgical extent. The time for lobectomy was significantly shorter in the advanced bipolar group (33.8±6.4 vs. 41.9±9.0 minutes, P=0.002). The number of camera cleanings was significantly lower in the advanced bipolar group (2.9±1.6 vs. 5.8±2.5 times, P<0.001). Estimated blood loss was also significantly less in the advanced bipolar group (11.5±17.3 vs. 81.8±99.5 mL, P=0.004). Postoperative hospital stays, drainage, pain score, laboratory findings, and complications were not significantly different between the two groups. According to this study, advanced bipolar device showed better performance, with a shorter operation time, less camera cleaning, and less blood loss. We suggest that advanced bipolar device can be a better choice in TOETVA. ClinicalTrials.gov identifier: NCT04320901.


Methods in molecular surgical pathology.
Nucleic acids (DNA and RNA) contain the basic information for the transcription and translation of the genetic information into the functional cell protein products. To obtain tissue materials for suitable extraction of these cellular components, proper preservation and storage are necessary for both fresh and archival materials. Techniques for nucleic acid analysis are fundamentally based on complementarity between target and probe nucleotide sequences called hybridization. These are aided by the discovery of polymerase chain reaction that allow for specific amplification of target nucleic acid sequences for detection and enhancing yields from small and precious specimens. These techniques, along with protein analysis by Western blotting, require validation, optimization, laboratory quality control, and assurance for competency. Interpretative criteria for each test according to accepted guidelines are necessary for clinical diagnostic purposes. High throughput technologies of nucleic acid and protein analyses for the discovery of new markers and understanding biological processes and pathways are also highlighted for their potential impact on surgical pathology practice.


Identification with sports teams by fans of women's sports.
Previous studies on why sports fans identify with a particular team have focused on fans of men's sports teams. This study examined why fans favor a particular women's sports team. Based on survey responses from 273 self-identified fans of women's sports, athletes are most frequently cited as the reason for choosing a favorite women's sports team.


Epidemiology of Musculoskeletal Symptoms Among Milkers and Dairy Farm Characteristics in Sweden and Germany.
International studies have shown that musculoskeletal symptoms (MSS) and disorders (MSD) are common among dairy farm milkers. Although dairy production is diverse, it has so far not been possible to explain the high risk by production parameters. Two national studies carried out under similar conditions were the incentive to merge the data and increase the sample size. The Standardized Nordic Questionnaire was used to assess MSS prevalence among 92 Swedish and 116 German male and female milkers. Eighty-four percent and 85% of the Swedish and German milkers reported MSS in at least one body part. Highest prevalence was reported in the lower back, shoulder, and neck. Females showed a significantly higher risk of MSS. Apart from that, small significant influence of MSS was found for other risk factors. These findings indicate that technical and organizational modifications of the work place design in milking parlors are needed.


LBMR: Load-Balanced Multipath Routing for Wireless Data-Intensive Transmission in Real-Time Medical Monitoring.
In wireless networks, low-power Zigbee is an excellent network solution for wireless medical monitoring systems. Medical monitoring generally involves transmission of a large amount of data and easily causes bottleneck problems. Although Zigbee's AODV mesh routing provides extensible multi-hop data transmission to extend network coverage, it originally does not, and needs to support some form of load balancing mechanism to avoid bottlenecks. To guarantee a more reliable multi-hop data transmission for life-critical medical applications, we have developed a multipath solution, called Load-Balanced Multipath Routing (LBMR) to replace Zigbee's routing mechanism. LBMR consists of three main parts: Layer Routing Construction (LRC), a Load Estimation Algorithm (LEA), and a Route Maintenance (RM) mechanism. LRC assigns nodes into different layers based on the node's distance to the medical data gateway. Nodes can have multiple next-hops delivering medical data toward the gateway. All neighboring layer-nodes exchange flow information containing current load, which is the used by the LEA to estimate future load of next-hops to the gateway. With LBMR, nodes can choose the neighbors with the least load as the next-hops and thus can achieve load balancing and avoid bottlenecks. Furthermore, RM can detect route failures in real-time and perform route redirection to ensure routing robustness. Since LRC and LEA prevent bottlenecks while RM ensures routing fault tolerance, LBMR provides a highly reliable routing service for medical monitoring. To evaluate these accomplishments, we compare LBMR with Zigbee's AODV and another multipath protocol, AOMDV. The simulation results demonstrate LBMR achieves better load balancing, less unreachable nodes, and better packet delivery ratio than either AODV or AOMDV.


[Problems of structural and functional identification of biological tissues].
The theoretical methods of identification of topological and functional parameters for biological tissues, such as myocardium, are considered. Among the unknown topological parameters are the dimension and connectivity of a network, and the unknown functional parameters include the electrical resistance of the cellular membrane and cytoplasm. Experimentally known data are the sizes of cells (length and diameter), the input resistance of tissue, and also the field of electrical potential formed by a "dot" current source (by an intracellular microelectrode).


Detection limit for rate fluctuations in inhomogeneous Poisson processes.
Estimations of an underlying rate from data points are inevitably disturbed by the irregular occurrence of events. Proper estimation methods are designed to avoid overfitting by discounting the irregular occurrence of data, and to determine a constant rate from irregular data derived from a constant probability distribution. However, it can occur that rapid or small fluctuations in the underlying density are undetectable when the data are sparse. For an estimation method, the maximum degree of undetectable rate fluctuations is uniquely determined as a phase transition, when considering an infinitely long series of events drawn from a fluctuating density. In this study, we analytically examine an optimized histogram and a Bayesian rate estimator with respect to their detectability of rate fluctuation, and determine whether their detectable-undetectable phase transition points are given by an identical formula defining a degree of fluctuation in an underlying rate. In addition, we numerically examine the variational Bayes hidden Markov model in its detectability of rate fluctuation, and determine whether the numerically obtained transition point is comparable to those of the other two methods. Such consistency among these three principled methods suggests the presence of a theoretical limit for detecting rate fluctuations.


Reactions of liquid and solid aluminum clusters with N2: the role of structure and phase in Al114 (+), Al115 (+), and Al117 (+).
Kinetic energy thresholds have been measured for the chemisorption of N2 onto Al114 (+), Al115 (+), and Al117 (+) as a function of the cluster's initial temperature, from around 200 K up to around 900 K. For all three clusters there is a sharp drop in the kinetic energy threshold of 0.5-0.6 eV at around 450 K, that is correlated with the structural transition identified in heat capacity measurements. The decrease in the thresholds corresponds to an increase in the reaction rate constant, k(T) at 450 K, of around 10(6)-fold. No significant change in the thresholds occurs when the clusters melt at around 600 K. This contrasts with behavior previously reported for smaller clusters where a substantial drop in the kinetic energy thresholds is correlated with the melting transition.


Oxidants, ATP depletion, and endothelial permeability to macromolecules.
Oxidants can reversibly increase the permeability of endothelium to ions and macromolecules. Oxidants also deplete ATP in cultured endothelial cells. We asked if oxidant-mediated ATP depletion, alone, accounted for the effects of oxidants on endothelial permeability to macromolecules. When porcine pulmonary artery endothelial cells were exposed to 2.5 mmol/LH2O2, ATP was depleted to 31.7% +/- 1.8% of control within 15 minutes and was reduced to 23.1% +/- 2.0% of control after 30 minutes. To determine if this magnitude of ATP depletion could account for the oxidant-induced increase in endothelial permeability to macromolecules, we measured ATP in endothelial cells exposed to metabolic inhibitors of ATP production. We then measured the effects of these metabolic inhibitors on endothelial monolayer permeability to macromolecules. ATP levels were reduced to 44% +/- 4% of control by 12 mmol/L deoxyglucose (DOG) in the absence of glucose and to 2% +/- 1.3% of control by DOG with 25 nmol/L antimycin A in the absence of glucose. Reduction of endothelial cell ATP to these levels with the metabolic inhibitors did not alter the flux of albumin or dextran across the endothelial monolayers. Thus ATP depletion, by itself, does not explain oxidant-induced changes in endothelial permeability to macromolecules.


Gastric emptying of milk feedings in infants and children. Anterior versus conjugate counting.
The radionuclide milk scan is a valuable tool for the evaluation of gastroesophageal reflux and gastric emptying in children. There is uncertainty as to whether anterior imaging alone is sufficient for determining gastric emptying in these patients. Twenty-five children underwent Tc-99m sulfur colloid milk scans with images acquired in the anterior and posterior projections. Calculations of the 1 hour and 2 hour percentage of gastric residual activity were performed using the anterior counts alone and the geometric mean of the anterior and posterior counts. The anterior and posterior images were visually assessed for the presence of gastroesophageal reflux. The means of the absolute differences at 1 and 2 hours for the two methods of gastric residual calculation were 4.1% +/- 2.1% and 3.4% +/- 2.8%, respectively. There was good correlation between the two methods at 1 and 2 hours with r values of 0.991 and 0.997 respectively. Gastroesophageal reflux was more obvious in the anterior images and three small episodes were only seen on the anterior view. Anterior images alone give reliable results for the determination of gastric emptying, and gastroesophageal reflux is more readily visualized anteriorly in the pediatric population.


Selective attention to stimulus features modulates interocular suppression.
Psychological and neurophysiological studies have shown that attention modulates various sorts of perceptual processing. Here, we report that attention affects the perceptual dominance of binocular rivalry. Experiments using a dichoptic masking paradigm revealed that when an observer was attending to one of the two orientations of the elements of a monocular texture, a texture briefly presented to the opposite eye suppressed the perception of the elements with the attended orientation, while the elements with the orientation which was ignored sustained their dominance. Moreover, subsequent experiments indicated that the suppression depended on the orientation of the texture elements constituting the mask, but was independent of their locations. These results suggest that attention to specific features modulates interocular suppression in a mode which is different from that found in a previous study [Ooi and He, 1999 Perception 28 551 -574].


Pioglitazone reduces blood pressure in non-dipping diabetic patients.
The association between insulin resistance and hypertension is firmly established and has been extensively investigated. Thiazolidinediones (TZD), a class of oral hypoglycemic agents that act as insulin sensitizers have been demonstrated, in many in vivo and in vitro studies, to possess antihypertensive properties. Whether the ability of TZD to lower blood pressure (BP) should be ascribed to a reduction of insulin resistance, or to a direct vasodilating effect, is matter of debate. Since blunted BP nocturnal dipping precedes overt hypertension and is associated with an increased risk of adverse cardiovascular events, we evaluated the pioglitazone effects on BP in non-dipper type 2 diabetic patients. Forty non-dipper diabetic patients were randomly assigned to metformin + placebo (M) or metformin + pioglitazone 30 mg (MP) and submitted to 24 hours blood pressure monitoring at the beginning and after 8 weeks. After 8 weeks of treatment in subjects on metformin + pioglitazone 30 mg (group MP1), we found a reduction of nocturnal blood pressure values (mean nocturnal systolic BP 128.05+/- 1.23 vs 122.8+/-2.3 mmHg; p<0.02; mean nocturnal diastolic BP 81.2+/-0.99 vs 75.65+/-0.93 mmHg; p<0.005). The observed improvements in BP were independent from changes in metabolic parameters. The obtained data show that pioglitazone was effective in reducing BP values in non-dipping diabetic patients. The reduction of BP values was independent from amelioration of the metabolic picture: that suggest the hypothesis that these ameliorations may be also due to a direct antihypertensive action exerted by pioglitazone.


Brain metastasis in lung cancer: Building a molecular and systems-level understanding to improve outcomes.
Lung cancer is a clinically difficult disease with rising disease burden around the world. Unfortunately, most lung cancers present at a clinically advanced stage. Of these cancers, many also present with brain metastasis which complicates the clinical picture. This review summarizes current knowledge on the molecular basis of lung cancer brain metastases. We start from the clinical perspective, aiming to provide a clinical context for a significant problem that requires much deeper scientific investigation. We review new research governing the metastatic process, including tumor cell signaling, establishment of a receptive tumor niches in the brain and evaluate potential new therapeutic options that take advantage of these new scientific advances. Lung cancer remains the largest single cause of cancer mortality in the United States (Siegel et al., 2015). This continues to be the clinical picture despite significant advances in therapy, including the advent of targeted molecular therapies and newly adopted immunotherapies for certain subtypes of lung cancer. In the vast majority of cases, lung cancer presents as advanced disease; in many instances, this advanced disease state is intimately associated with micro and macrometastatic disease (Goldberg et al., 2015). For both non-small cell lung cancer and small cell lung cancer patients, the predominant metastatic site is the brain, with up to 68% of patients with mediastinal lymph node metastasis eventually demonstrating brain metastasis (Wang et al., 2009).The frequency (incidence) of brain metastasis is highest in lung cancers, relative to other common epithelial malignancies (Schouten et al., 2002). Other studies have attempted to predict the risk of brain metastasis in the setting of previously non-metastatic disease. One of the largest studies to do this, analyzing historical data from 1973 to 2011 using the SEER database revealed a 9% risk of patients with previously non-metastatic NSCLC developing brain metastasis over the course of their disease, while 18% of small cell lung cancer patients without previous metastasis went on to develop brain metastasis as their disease progressed (Goncalves et al., 2016).The reasons underlying this predilection for the central nervous system, as well as the recent increase in the frequency of brain metastasis identified in patients remain important questions for both clinicians and basic scientists. More than ever, the question of how brain metastasis develop and how they can be treated and managed requires the involvement of interdisciplinary teams-and more importantly-scientists who are capable of thinking like clinicians and clinicians who are capable of thinking like scientists. This review aims to present a translational perspective on brain metastasis. We will investigate the scope of the problem of brain metastasis and the current management of the metastatic disease process in lung cancer. From this clinical starting point, we will investigate the literature surrounding the molecular underpinnings of lung tumor metastasis and seek to understand the process from a biological perspective to generate new hypotheses.


Shortening the incubation time for the combination disk diffusion extended-spectrum β-lactamase (ESBL) confirmation test: how far can we go?
The combination disk diffusion extended-spectrum β-lactamase (ESBL) confirmation test (CDT) is used for the confirmation of ESBL production in Enterobacteriaceae and usually takes 16-20 h to results. In this study, we searched for the shortest possible incubation time without a reduction in reliability. A total of 125 ESBL screening-positive isolates were subjected to CDT and were molecularly characterised by microarray. Inhibition zones were read every hour over 6-18 h of incubation. Concordance between earlier and 18-h readings was calculated for each hour. Results were validated on 224 isolates during routine clinical practice. For the initial 125 isolates, concordance (Cohen's κ) between the 6-h and 18-h readings was 0.88 [95% confidence interval (CI) 0.78-0.96; P <0.001]. The earliest time point for full concordance with the 18-h reading was 10 h. Validation of the 10-h reading for 224 clinical isolates resulted in a concordance of 0.99 (95% CI 0.98-1.0) between the 10-h and 18-h readings. Overall concordance on all 349 isolates was 0.99 (95% CI 0.97-1.0). Reading after 10 h of incubation has an excellent correlation with results after 18 h of incubation. This can significantly reduce the turnaround time for ESBL detection in laboratories with long opening hours or providing a 24/7 service. Consequently, there is a potential for implementing infection control measures up to 8 h earlier.


[Electrophysiological effects of neurotransmitters on pacemaker cells in guinea pig left ventricular outflow tract].
This study was designed to explore the innervation of autonomic nervous system and the distribution of receptors on pacemaker cell membrane in guinea pig left ventricular outflow tract (aortic vestibule). By using conventional intracellular microelectrode technique to record action potentials, autonomic neurotransmitters and antagonists were used to investigate the electrophysiological features and regularities of spontaneous activity of left ventricular outflow tract cells. Electrophysiological parameters examined were: maximal diastolic potential (MDP), amplitude of action potential (APA), maximal rate of depolarization (V(max)), velocity of diastolic depolarization (VDD), rate of pacemaker firing (RPF), 50% and 90% of duration of action potential (APD(50) and APD(90)). The results are listed below: (1) Perfusion with 100 mumol/L isoprenaline (Iso) resulted in a significant increase in V(max) (P <0.05), VDD, RPF, and APA (P <0.01), a notable decrease in MDP (P<0.05), and also a marked shortening in APD(50) (P<0.01). Pretreatment with Iso (100 mumol/L), propranolol (5 mumol/L) significantly decreased RPF and VDD (P<0.01), decreased APA, MDP and V(max) (P<0.01) notably, prolonged APD(50) (P<0.01) and APD(90) (P<0.05) markedly. (2) Application of 100 mumol/L epinephrine (E) resulted in a significant increase in VDD (P<0.05), RPF (P<0.001), V(max) (P<0.05) and APA (P<0.001), and a notable shortening in APD(50) and APD(90) (P<0.05). (3) Perfusion with 100 mumol/L norepinephrine (NE) led to a significant increase in VDD, RPF, APA and V(max) (P<0.05), and a marked shortening in APD(50) (P<0.05). Pretreatment with NE (100 mumol/L), phentolamine (100 mumol/L) significantly decreased RPF and VDD, MDP and APA (P<0.01), decreased V(max) notably (P<0.05), prolonged APD(50) and APD(90) markedly (P<0.01). (4) During perfusion with 10 mmol/L acetylcholine (ACh), VDD and RPF slowed down notably (P<0.05), APA decreased significantly (P<0.001), V(max) slowed down notably (P<0.01), APD50 shortened markedly (P<0.05), Atropine (10 mmol/L) antagonized the effects of ACh (10 mumol/L) on APD(50) (P<0.05). These results suggest that there are probably alpha-adrenergic receptor (alpha-AR), beta-adrenergic receptor (beta-AR) and muscarinic receptor (MR) on pacemaker cell membrane of left ventricular outflow tract in guinea pig. The spontaneous activities of left ventricular outflow tract cells are likely regulated by sympathetic and parasympathetic nerves.


Interhemispheric amplitude symmetry in the EEGs of normal full term, low risk premature, and trisomy-21 infants.
RMS measurements of amplitude symmetry were calculated for samples of typical active and quiet sleep periods in 12 normal full term, 5 premature and 7 Trisomy-21 infants from recordings obtained at 1, 4, 12 26 and 52 weeks post term. The frequency distributions of the symmetry data for each group did not deviate significantly from the expected normal distributions. The mean symmetry ratios were not significantly different among the 3 groups. It was concluded that the EEGs of the 3 groups are characterized by amplitude symmetry in the first year of life. The possibility that symmetry data may be used for classification of abnormal EEGs was discussed.


Coronary angiography in atrial myxoma: findings in nine cases.
We report the findings on selective coronary angiography in nine patients with atrial myxomas. The angiograms were obtained because the patients were suspected of having coronary artery disease. In each case, the diagnosis of myxoma had been made earlier by echocardiography. Coronary angiography in five (55%) of the nine patients showed neovascularity in the tumor without calcification. In one patient, the angiogram showed a varix of the myocardium at the base of the tumor. The angiograms in three (33%) of the nine patients did not show neovascularity but showed tumoral calcification. Six (67%) of the nine patients had significant coronary artery disease that required coronary artery bypass grafting along with resection of the myxoma. These data suggest that the incidence of neovascularity in atrial myxomas is higher than previously reported. Furthermore, a significant number of this older population presented with operable artery disease as well as atrial myxoma.


Immunohistochemical localization of renin in renal tumors.
Immunoperoxidase staining for renin was performed with renal tumors, including juxtaglomerular (JG) tumor, Wilms' tumors, renal adenocarcinomas, renal oncocytomas, and cortical adenomas. Compared with the JG apparatus adjacent to the glomerulus, JG tumor cells were less darkly but diffusely stained for renin. One of five Wilms' tumors revealed more numerous renin-containing tumor cells than the adjacent renal cortex, whereas three of ten renal adenocarcinomas and two of three renal oncocytomas revealed only focally renin-positive tumor cell cytoplasms. None of six cortical adenomas were positive for renin. With available fresh tumor tissue, renin activity was studied by measuring newly formed angiotensin I by radioimmunoassay. JG tumor contained markedly elevated renin activity, whereas one Wilms' tumor and two renal adenocarcinomas contained no more than 2% of renin activity of the renal cortex, more than 50% of which was inactive renin. These findings suggest that the JG tumor elaborates enormous amounts of active renin, whereas other renal tumors produce lesser amounts of renin, more than half of which is inactive renin.


Enhancement of Nile blue derivative-induced photocytotoxicity by nigericin and low cytoplasmic pH.
The mechanism of photocytotoxicity mediated by a lysosomotropic photosensitizer, Nile blue derivative (NBS-61), in relation to lysosome destruction was examined by lowering the intracellular pH with low extracellular pH and an ionophore, nigericin. The treatment performed after photoirradiation had minimal effect on the cytotoxicity. However, when the treatment was initiated before photoirradiation, it caused a three orders of magnitude enhancement on cytotoxicity with a two orders of magnitude enhancement by nigericin alone. This effect on cytotoxicity resembles closely that observed on photosensitization mediated by chloroaluminum phthalocyanine. The enhancement in this case has been attributed to the synergistic interaction between photodamage and perturbation of ion transports across mitochondrial or plasma membranes by nigericin. Because these are not the main sites of localization for Nile blue photosensitizers nor their initial targets of photocytotoxic action, data from the present study suggest the possibility of an intracellular dye translocation induced by nigericin, which redistributes the Nile blue photosensitizer from lysosomes to other sites, as a possible cause of the enhancement of cytotoxicity.


Echocardiographic characteristics of chickens with ascites syndrome.
1. B- and M-mode echocardiography was used to compare cardiac function in broilers with spontaneous ascites syndrome with that of normal chickens. 2. Thirty ascitic chickens and 15 normal chickens aged three, 4, 5, and 6 weeks from the same flock (180 birds in total) were examined. They were restrained gently in a natural standing position, and echocardiographs were obtained from a 7.0-MHz linear transducer placed on the left pectoral apterium. Indices of cardiac structure and functioning were calculated from the echocardiographs, and some were normalised to body weight. Heart rate was also measured. 3. All cardiac structural indices in both ascitic and normal chickens increased with age. Compared with normal chickens, right ventricular diameter at the end of systole in ascitic chickens was greater at 4, 5 and 6 weeks of age. Ventricular septal thickness at the end of both systole and diastole was greater in ascitic chickens at 5 and 6 weeks. Left ventricular free wall thickness at the end of diastole was less in ascitic chickens at 3 weeks. However, all the structural indices decreased with age after normalisation with body weight. 4. The heart rate of ascitic chickens was lower at 4, 5 and 6 weeks. Normalised left ventricular fractional shortening was lower in ascitic chickens at 4, 5 and 6 weeks, as was normalised right ventricular fractional shortening. Incrassation of the ventricular septum (Delta T), which changed little in normal chickens, was less at 4, 5 and 6 weeks in ascitic chickens. Left ventricular fractional shortening, right ventricular fractional shortening and Delta T were all negatively correlated with ascites heart index at all ages. 5. Taken together the results suggest heart failure of both ventricle, but that right ventricular dysfunction is more extensive than left ventricular dysfunction. We suggest that secondary pulmonary hypertension would result in these ascitic chickens due to volume overload.


The persistence of biofilm-associated antibiotic resistance of Staphylococcus aureus isolated from clinical bovine mastitis cases in Australia.
The aim of this investigation was to determine the persistence of biofilm-associated antibiotic resistance developed by methicillin-sensitive Staphylococcus aureus (MSSA), of different capsular types, during biofilm formation. Because of superiority of the tissue culture plate (TCP) over the Congo Red Agar (CRA) method for measuring biofilm formation, it was used to determine the persistence of the antibiotic resistance developed by the isolates in biofilms. The antibiotic resistance was found to persist for 3-4 wk post-propagation as planktonic subcultures. Interestingly, some strains even developed resistance to vancomycin and/or teicoplanin. However, no association of either biofilm formation or persistent antibiotic resistance with the major capsular phenotype was observed. These observations highlight the potential significance of (a) determining the antibiograms of S. aureus subcultured from biofilms developed in vitro using the TCP method as well as from planktonic cultures for formulation of an optimal therapeutic strategy, and (b) continuing to identify predominant non-capsular antigens contributing to biofilm formation, regardless of the capsular phenotype for the development of an effective potentially broad-spectrum vaccine for prevention of bovine mastitis caused by S. aureus.


Advances in the clinical applications of exhaled nitric oxide measurements.
This article focuses on recent data which highlight the clinical settings in which exhaled nitric oxide (F(E)NO) is potentially helpful, or not, as a clinical tool. It is becoming clearer that, selectively applied, F(E)NO measurements can provide reliable clinical guidance, particularly when values are low. Such values are associated with high negative predictive values (>90%). Increased F(E)NO levels are associated with much more modest positive predictive values (75%-85%) and these are less reliable. These general principles apply when diagnosing steroid responsiveness in relation to asthma, chronic cough, and COPD. Although randomised trials do not support routine use of exhaled NO measurements in uncomplicated bronchial asthma, there is evidence that in patients with difficult asthma, or asthma associated with pregnancy, F(E)NO enhances overall management, and the decision to commence or increase inhaled steroid therapy (yes/no) may be made more accurately. Exhaled NO is potentially relevant in the assessment of occupational asthma (serial measurements) and also in diagnosing bronchiolitis obliterans in lung transplant patients.