Carbonyls and Carbon Monoxide Emissions from Electronic Cigarettes Affected by Device Type and Use Patterns.
Dangerous levels of harmful chemicals in electronic cigarette (e-cigarette) aerosols were reported by several studies, but variability in e-cigarette design and use patterns, and a rapid development of new devices, such as JUUL, hamper efforts to develop standardized testing protocols and understand health risks associated with e-cigarette use. In this study, we investigated the relative importance of e-cigarette design, power output, liquid composition, puff topography on e-cigarette emissions of carbonyl compounds, carbon monoxide (CO), and nicotine. Four popular e-cigarette devices representing the most common e-cigarette types (e.g., cig-a-like, top-coil, 'mod', and 'pod') were tested. Under the tested vaping conditions, a top-coil device generated the highest amounts of formaldehyde and CO. A 'pod' type device (i.e., JUUL) emitted the highest amounts of nicotine, while generating the lowest levels of carbonyl and CO as compared to other tested e-cigarettes. Emissions increased nearly linearly with puff duration, while puff flow had a relatively small effect. Flavored e-liquids generated more carbonyls and CO than unflavored liquids. Carbonyl concentrations and CO in e-cigarette aerosols were found to be well correlated. While e-cigarettes emitted generally less CO and carbonyls than conventional cigarettes, daily carbonyl exposures from e-cigarette use could still exceed acute exposure limits, with the top-coil device potentially posing more harm than conventional cigarettes.


Endotracheal intubation and Venturi (jet) ventilation for laser microsurgery of the larynx.
Meeting the exacting requirements for microsurgery of the larynx is a challenge for the anesthesiologist. To accomplish, the necessary dissection, the otolaryngologist has several requirements. They are a quiet relaxed field, excellent illumination with magnification, binocular vision for depth perception, and, above all, an unobstructed field. The management of anesthesia for suspension microsurgery on the larynx presents many problems, the most vexing of which is the fact that the otolaryngologist and anesthesiologist are in competition for access to the patient's airway. In sharing this, neither has been able to perform with the degree of control that he would like due to either inadequate operating conditions or insufficient access to ventilatory mechanisms. Several anesthetic techniques have been used for inspection or operative laryngoscopy: topical anesthesia, apneic techniques, translaryngeal topical anesthesia, chest respirator, neuroleptanalgesia, and general endotracheal anesthesia with muscle relaxants. The latter has proven most popular, particularly in children, because ventilation and surgical conditions are considered to be most controllable. However, the presence of the requisite endotracheal tube obscures the full view of the larynx and vocal cords, and the tube may itself become obstructed. Additionally, use of the laser involves the further risk of heat effects on the endotracheal tube if the beam hits the tube. This report presents our experience and development of the combined technique of endotracheal intubation and Venturi (jet) ventilation. We believe it represents the safest available approach while providing near ideal working conditions for the otolaryngologist during laser microsurgery of the larynx.


Regulation and action of early growth response 1 in bovine granulosa cells.
Fibroblast growth factors (FGF) modify cell proliferation and differentiation through receptor tyrosine kinases, which stimulate the expression of transcription factors including members of the early growth response (EGR) family. In ovarian granulosa cells, most FGFs activate typical response genes, although the role of EGR proteins has not been described. In the present study, we determined the regulation of EGR mRNA by FGFs and explored the role of EGR1 in the regulation of FGF-response genes. Addition of FGF1, FGF2, FGF4 or FGF8b increased EGR1 and EGR3 mRNA levels, whereas FGF18 increased only EGR1 mRNA abundance. No mRNA encoding EGR2 or EGR4 was detected. Overexpression of EGR1 increased EGR3 mRNA levels as well as the FGF-response genes SPRY2, NR4A1 and FOSL1 and also increased the phosphorylation of MAPK3/1. Knockdown of EGR3 did not alter the ability of FGF8b to stimulate SPRY2 mRNA levels. These data demonstrate the regulation of EGR1 and EGR3 mRNA abundance by FGFs in granulosa cells and suggest that EGR1 is likely an upstream component of FGF signaling in granulosa cells.


Improved Intraoperative Visualization of Nerves through a Myelin-Binding Fluorophore and Dual-Mode Laparoscopic Imaging.
The ability to visualize and spare nerves during surgery is critical for avoiding chronic morbidity, pain, and loss of function. Visualization of such critical anatomic structures is even more challenging during minimal access procedures because the small incisions limit visibility. In this study, we focus on improving imaging of nerves through the use of a new small molecule fluorophore, GE3126, used in conjunction with our dual-mode (color and fluorescence) laparoscopic imaging instrument. GE3126 has higher aqueous solubility, improved pharmacokinetics, and reduced non-specific adipose tissue fluorescence compared to previous myelin-binding fluorophores. Dosing and kinetics were initially optimized in mice. A non-clinical modified Irwin study in rats, performed to assess the potential of GE3126 to induce nervous system injuries, showed the absence of major adverse reactions. Real-time intraoperative imaging was performed in a porcine model. Compared to white light imaging, nerve visibility was enhanced under fluorescence guidance, especially for small diameter nerves obscured by fascia, blood vessels, or adipose tissue. In the porcine model, nerve visualization was observed rapidly, within 5 to 10 minutes post-intravenous injection and the nerve fluorescence signal was maintained for up to 80 minutes. The use of GE3126, coupled with practical implementation of an imaging instrument may be an important step forward in preventing nerve damage in the operating room.


The rat gracile nucleus in vitro: I. Evidence for a GABA-mediated depolarisation of the dorsal column afferents.
The preparation and maintenance of a novel slice of the rat gracile nucleus is described. The slice includes both gracile nuclei as well as an intact afferent input from the dorsal columns. Extracellular recording revealed that a compound tract action potential (CAP) could be recorded from the gracile nucleus following stimulation of the ipsilateral dorsal column. The CAP was followed by slower field potentials which are thought to be dependent on synaptic activity. Four consequences of stimulating the dorsal columns were observed: (1) a subsequent CAP was conducted more rapidly along the afferents whether it travelled in an orthodromic or antidromic direction; (2) the amplitude of a subsequent orthodromic CAP was reduced; (3) the amplitude of a subsequent submaximal antidromic CAP was increased; and (4) a slow positive potential could be recorded from the dorsal columns. All 4 phenomena had comparable time-courses and were similarly sensitive to agents which reduce synaptic transmission. Pharmacological evidence indicated that all 4 phenomena were mediated by GABA. It is suggested that a GABA-mediated depolarization of the gracile afferents can be evoked in this slice.


Environmental Survey of Drinking Water Sources in Kampala, Uganda, during a Typhoid Fever Outbreak.
In 2015, a typhoid fever outbreak began in downtown Kampala, Uganda, and spread into adjacent districts. In response, an environmental survey of drinking water source types was conducted in areas of the city with high case numbers. A total of 122 samples was collected from 12 source types and tested for Escherichia coli, free chlorine, and conductivity. An additional 37 grab samples from seven source types and 16 paired large volume (20 liter) samples from wells and springs were also collected and tested for the presence of Salmonella enterica serovar Typhi. Escherichia coli was detected in 60% of kaveras (drinking water sold in plastic bags) and 80% of refilled water bottles; free chlorine was not detected in either source type. Most jerry cans (68%) contained E. coli and had free chlorine residuals below the WHO-recommended level of 0.5 mg/liter during outbreaks. Elevated conductivity readings for kaveras, refilled water bottles, and jerry cans (compared to treated surface water supplied by the water utility) suggested that they likely contained untreated groundwater. All unprotected springs and wells and more than 60% of protected springs contained E. coli Water samples collected from the water utility were found to have acceptable free chlorine levels and no detectable E. coli While S Typhi was not detected in water samples, Salmonella spp. were detected in samples from two unprotected springs, one protected spring, and one refilled water bottle. These data provided clear evidence that unregulated vended water and groundwater represented a risk for typhoid transmission.IMPORTANCE Despite the high incidence of typhoid fever globally, relatively few outbreak investigations incorporate drinking water testing. During waterborne disease outbreaks, measurement of physical-chemical parameters, such as free chlorine residual and electrical conductivity, and of microbiological parameters, such as the presence of E. coli or the implicated etiologic agent, in drinking water samples can identify contaminated sources. This investigation indicated that unregulated vended water and groundwater sources were contaminated and were therefore a risk to consumers during the 2015 typhoid fever outbreak in Kampala. Identification of contaminated drinking water sources and sources that do not contain adequate disinfectant levels can lead to rapid targeted interventions.


The unenlarged lymph nodes of HIV-1-infected, asymptomatic patients with high CD4 T cell counts are sites for virus replication and CD4 T cell proliferation. The impact of highly active antiretroviral therapy.
The efficacy of triple drug therapy for HIV-1 infection encourages its early use to prevent damage to the immune system. We monitored the effects of such therapy on 12 patients with 14-75-mo histories of minimal disease, i.e., CD4+ counts constantly >500/microl and little or no lymph node enlargement. In this way, we could first determine the extent of viral replication and immunoarchitectural changes in unenlarged nodes early in disease, and second follow the response to triple therapy in plasma and lymphoid tissue in tandem. As is known for lymph nodes with more advanced disease, the germinal centers showed productively infected T cells, i.e., CD4+CD1a-CD68- cells labeling intensely for HIV-1 RNA after in situ hybridization. The unenlarged nodes also showed extensive HIV-1 RNA retention on a well-preserved, follicular dendritic cell (FDC) network, and the follicles were abnormal. There were numerous CD8+ cells, many expressing TIA-1 granule antigen. Also, in contrast to normal follicles, CD4+ T cell proliferation was active, with marked increases in the number of cycling, Ki-67+CD4+CD45R0+ cells. After 28 d and 3 mo of therapy, productively infected T cells decreased dramatically and often were not apparent. The labeling of the FDC network for viral RNA also decreased, but not for gag protein. We conclude that HIV-1 replicates and accumulates in lymphoid organs before damage of the immune system, that at this stage of disease de novo production of T cells occurs in the lymphoid tissue, and that the infection is sensitive to triple drug therapy in both plasma and lymph nodes.


[Investigation of operative process in treating lumbar intervertebral disc protrusion in aged patients].
To investigate the operative management and surgical techniques for lumber disc herniation (LDH) in aged patients (>or=65 years). From 2005 to 2010,the data of 43 patients with LDH underwent surgical treatment were retrospectively analyzed. There were 25 males and 18 females,aged from 65 to 70 years old with an average of 67.6 years. The course of disease was from 6 weeks to 7 years with an average of 10.2 years. Fenestratiodn discectomy or extended fenestration discectomy and unilateral or bilateral fenestration were used according to the conditions of location,type of herniated macleos polposus and nerve root compression. Among the patients,the nerve root canal was enlarged,hyperplastic osteophyma and soft tissue were removed, bilateral articular process was reserved in order to maintain the stability of the lumbar segment. All the patients were followed up from 1.2 to 5.2 years. According to the criteria of HU you-gu, 25 cases got excellent results, 15 good, 2 fair and 1 poor. No infection or nerve injury was found. Nerve function of patients had a normal or near normal recovery. For the treatment of LDH in aged patents,it is key that reasonably choose the operative method, completely remove the hyperplasy of diseased region and enlarge the nerve root canal, thoroughly loose the nerve root.


Fertilization-dependent auxin response in ovules triggers fruit development through the modulation of gibberellin metabolism in Arabidopsis.
Fruit development is usually triggered by ovule fertilization, and it requires coordination between seed development and the growth and differentiation of the ovary to host the seeds. Hormones are known to synchronize these two processes, but the role of each hormone, and the mechanism by which they interact, are still unknown. Here we show that auxin and gibberellins (GAs) act in a hierarchical scheme. The synthetic reporter construct DR5:GFP showed that fertilization triggered an increase in auxin response in the ovules, which could be mimicked by blocking polar auxin transport. As the application of GAs did not affect auxin response, the most likely sequence of events after fertilization involves auxin-mediated activation of GA synthesis. We have confirmed this, and have shown that GA biosynthesis upon fertilization is localized specifically in the fertilized ovules. Furthermore, auxin treatment caused changes in the expression of GA biosynthetic genes similar to those triggered by fertilization, and also restricted to the ovules. Finally, GA signaling was activated in ovules and valves, as shown by the rapid downregulation of the fusion protein RGA-GFP after pollination and auxin treatment. Taken together, this evidence suggests a model in which fertilization would trigger an auxin-mediated promotion of GA synthesis specifically in the ovule. The GAs synthesized in the ovules would be then transported to the valves to promote GA signaling and thus coordinate growth of the silique.


Lysobacter oligotrophicus sp. nov., isolated from an Antarctic freshwater lake in Antarctica.
A Gram-stain-negative, non-spore-forming, rod-shaped, aerobic bacterium (strain 107-E2(T)) was isolated from freshwater samples containing microbial mats collected at a lake in Skarvsnes, Antarctica (temporary lake name, Lake Tanago Ike). Strain 107-E2(T) grew between 5 and 25 °C, with an optimum of 23 °C. Moreover, colony formation was observed on agar media even at -5 °C. The pH range for growth was between 6.0 and 9.0, with an optimum of pH 7.0-8.0. The range of NaCl concentration for growth was between 0.0 and 0.5% (w/v), with an optimum of 0.0%. No growth was observed in media containing organic compounds at high concentrations, which indicated that strain 107-E2(T) was an oligotroph. In the late stationary phase, strain 107-E2(T) produced a dark brown water-soluble pigment. Esterase, amylase and protease production was observed. Antimicrobial-lytic activities for Gram-negative bacteria and yeast were observed. Ubiquinone-8 was the major respiratory quinone. The major fatty acids were iso-C15:0, iso-C(17:1)ω9c and iso-C(15:1) at 5. The G+C content of genomic DNA was 66.1 mol%. Analysis of the 16S rRNA gene sequences revealed that strain 107-E2(T) belonged to the genus Lysobacter, and low DNA-DNA relatedness values with closely related species distinguished strain 107-E2(T) from recognized species of the genus Lysobacter. The phylogenetic situation and physiological characteristics indicated that strain 107-E2(T) should be classified as a representative of a novel species of the genus Lysobacter, for which the name Lysobacter oligotrophicus sp. nov. is proposed. The type strain is 107-E2(T) ( =JCM 18257(T) =ATCC BAA-2438(T)).


Thermodynamics of random reaction networks.
Reaction networks are useful for analyzing reaction systems occurring in chemistry, systems biology, or Earth system science. Despite the importance of thermodynamic disequilibrium for many of those systems, the general thermodynamic properties of reaction networks are poorly understood. To circumvent the problem of sparse thermodynamic data, we generate artificial reaction networks and investigate their non-equilibrium steady state for various boundary fluxes. We generate linear and nonlinear networks using four different complex network models (Erdős-Rényi, Barabási-Albert, Watts-Strogatz, Pan-Sinha) and compare their topological properties with real reaction networks. For similar boundary conditions the steady state flow through the linear networks is about one order of magnitude higher than the flow through comparable nonlinear networks. In all networks, the flow decreases with the distance between the inflow and outflow boundary species, with Watts-Strogatz networks showing a significantly smaller slope compared to the three other network types. The distribution of entropy production of the individual reactions inside the network follows a power law in the intermediate region with an exponent of circa -1.5 for linear and -1.66 for nonlinear networks. An elevated entropy production rate is found in reactions associated with weakly connected species. This effect is stronger in nonlinear networks than in the linear ones. Increasing the flow through the nonlinear networks also increases the number of cycles and leads to a narrower distribution of chemical potentials. We conclude that the relation between distribution of dissipation, network topology and strength of disequilibrium is nontrivial and can be studied systematically by artificial reaction networks.


Effect of bovine neutrophil maturity on phagocytosis.
The ability of immature circulating neutrophils to phagocytose foreign particles was determined. One quarter of each of 4 cows, which were free of mastitis and pathogens and had milk somatic cell counts of less than 1 X 10(6) cells/ml, was infused with endotoxin of Escherichia coli (0.5 mg in 3 ml of saline solution) to induce a milk leukocytosis and a shift to the left in circulating leukocytes. Milk samples were taken from the infused and one uninfused quarter before and after infusion. Blood samples were collected at 9 hours after infusion, at 2-hour intervals from 13 to 21 hours, and at 36 hours after infusion. Phagocytosis was determined by incubating whole blood with yeast cells and determining the precentage of neutrophils phagocytosing and the number of yeast cells per neutrophil. Milk somatic cells increased from an average of less than 1.0 X 10(6) cells/ml before infusion to 37.0 X 10(6) cells/ml at the next milking (postinfusion hour 11). Circulating immature neutrophils increased from 7.6% before infusion to 56.6% at postinfusion hour 21. The percentage of neutrophils phagocytosing was 99 to 100 throughout the study. Number of yeast cells per neutrophil (mean phagocytosis) decreased from 6.5 before infusion was done to 5.2 after infusion. However, there was no correlation between percentage of immature neutrophils and mean phagocytosis. The decrease in yeast cells per neutrophil was attributed to the decrease in concentration of neutrophils and yeast cells in the in vitro procedure (r = 0.50). Apparently the immature neutrophils that appear after depletion of the mature form are as phagocytic as the mature neutrophils.


Modulation of murine complement receptor type 2 (CR2/CD21) ectodomain shedding by its cytoplasmic domain.
Ectodomain shedding is a mechanism that regulates numerous functions of cell surface proteins. The extracellular domain of the human complement receptor 2 (CR2/CD21) is released by proteolytic cleavage as a soluble protein through a variety of stimuli including the thiol antioxidants N-acetylcysteine (NAC) and glutathione (GSH), and the oxidant pervanadate (PV). In addition, PV mimics B cell antigen receptor (BCR) signaling. Here, we show that murine CD21 is shed upon those stimuli and that the cytoplasmic domain is an important modulator for CD21-shedding. B cells expressing a mutant CD21 cytoplasmic domain with only three amino acids (KHR) showed increased CD21-shedding and required lower stimuli concentrations. At lower PV concentrations, wildtype CD21 was up-regulated on the cell surface, whereas at higher PV concentrations the ectodomain was shed. These findings further indicate that GSH and NAC utilize different pathways than PV to activate CD21-shedding. Altogether, as pre-activated B cells express higher CD21 levels than resting mature B cells or fully activated and antigen-experienced B cells, we suggest CD21-shedding to be a mechanism to fine-tune B cell activation.


The impact of lockdowns during the COVID-19 pandemic on fertility intentions.
Lockdown edicts during the COVID-19 pandemic have led to concerns about consequences for childbirth plans and decisions. Robust empirical research to either refute or confirm these concerns, however, is lacking. To evaluate the causal impact of lockdowns on fertility, we exploited a large sample of Australians (aged 18-45) from a nationally representative household panel survey and leveraged variation from a unique natural experiment that occurred in Australia in 2020: a lockdown imposed in the state of Victoria, but not elsewhere in Australia. Difference-in-differences models were estimated comparing changes in fertility intentions of persons who resided in Victoria during lockdown, or within four weeks of the lockdown being lifted, and those living elsewhere in Australia. Results revealed a significantly larger decline in reported intentions of having another child among women who lived through the protracted lockdown. The average effect was small, with fertility intentions estimated to fall by between 2.8% and 4.3% of the pre-pandemic mean. This negative effect was, however, more pronounced among those aged over 35 years, the less educated, and those employed on fixed-term contracts. Impacts on men's fertility intentions were generally negligible, but with a notable exception being Indigenous Australians.


[Diagnosis and treatment of complicated postnecrotic cysts of pancreas].
Experience of complex treatment of 137 patients with complicated postnecrotic pancreatic cysts (PPC) is analyzed. Indications to different surgical methods are formulated differentially depending on complications of cysts, localization, sizes, "maturity" of cyst walls, communication with main pancreatic duct. Treatment of festered PPC should be started with minimally-invasive methods; at negative result the omentobursocystostomy with staged endoscopic sanations should be done that permits to decrease the number of postoperative complications and to reduce lethality from 14.3 to 4.5%. Resection of pancreas along with cyst is the operation of choice at pancreatic cysts complicated with bleeding; lethality has been reduced from 28.6 to 5.6%. Perforation of cysts into abdominal cavity is the indication to omentobursocystostomy with staged sanations of omental bursa, perforation into pleural cavity -- to distal resection of pancreas.


TCF21 Promotes Luminal-Like Differentiation and Suppresses Metastasis in Bladder Cancer.
Little is known regarding the subclone evolution process in advanced bladder cancer, particularly with respect to the genomic alterations that lead to the development of metastatic lesions. In this project, we identify gene expression signatures associated with metastatic bladder cancer through mRNA expression profiling of RNA isolated from 33 primary bladder cancer and corresponding lymph node (LN) metastasis samples. Gene expression profiling (GEP) was performed on RNA isolated using the Illumina DASL platform. We identified the developmental transcription factor TCF21 as being significantly higher in primary bladder cancer compared with LN metastasis samples. To elucidate its function in bladder cancer, loss- and gain-of-function experiments were conducted in bladder cancer cell lines with high and low expression of TCF21, respectively. We also performed GEP in bladder cancer cell lines following TCF21 overexpression. We identified 2,390 genes differentially expressed in primary bladder cancer and corresponding LN metastasis pairs at an FDR cutoff of 0.1 and a fold change of 1. Among those significantly altered, expression of TCF21 was higher in the primary tumor compared with LN metastasis. We validated this finding with qPCR and IHC on patient samples. Moreover, TCF21 expression was higher in luminal cell lines and knockdown of TCF21 increased invasion, tumor cell dissemination, and metastasis. In contrast, overexpression of TCF21 in highly metastatic basal bladder cancer cell lines decreased their invasive and metastatic potential. IMPLICATIONS: TCF21 is differentially overexpressed in primary bladder cancer compared with matched LN metastasis, with in vitro and in vivo studies demonstrating a metastasis suppressor function of this transcription factor.


[Efficacy of Distal Perfusion During Frozen Elephant Trunk Procedure:Continuous Perfusion Versus Intermittent Perfusion].
To compare the effectiveness of continuous distal perfusion( CDP) with that of intermittent distal perfusion( IDP) during frozen elephant trunk( FET) procedures. There were 54 patients in the CDP group and 15 patients in the IDP group. There were no significant differences in preoperative characteristics between the two groups, but dissection was more common in the IDP group than in the CDP group, and the maximum aneurysmal diameter was larger in the CDP group than in the IDP group. Emergency surgery was significantly more common in the IDP group than in the CDP group. Operating time, cardiopulmonary bypass time, lower body arrest time, and aortic cross-clamp time were significantly longer in the IDP group. Postoperative paraparesis occurred in one case in each group, and temporary paraparesis occurred in two cases in the CDP group, with no significant differences, including in mechanical ventilation time. There were two in-hospital deaths, one due to respiratory failure and one due to ischemic colitis, in the CDP group and one due to multiple organ failure in the IDP group. Postoperative liver and renal functions did not differ significantly between the two groups. IDP has proven to be almost as effective as CDP during FET for preventing spinal cord ischemia and maintaining respiratory, liver, and renal functions.


Imaging genetics and development: challenges and promises.
Excitement with the publication of the human genome has served as catalyst for scientists to uncover the functions of specific genes. The main avenues for understanding gene function have been in behavioral genetics on one end and on the other end, molecular mouse models. Attempts to bridge these approaches have used brain imaging to conveniently link anatomical abnormalities seen in knockout/transgenic mouse models and abnormal patterns of brain activity seen in humans. Although a convenient approach, this article provides examples of challenges for imaging genetics, its application to developmental questions, and promises for future directions. Attempts to link genes, brain, and behavior using behavioral genetics, imaging genetics, and mouse models of behavior are described. Each of these approaches alone, provide limited information on gene function in complex human behavior, but together, they are forming bridges between animal models and human psychiatric disorders.


An anemia of Alzheimer's disease.
Lower hemoglobin is associated with cognitive impairment and Alzheimer's disease (AD). Since brain iron homeostasis is perturbed in AD, we investigated whether this is peripherally reflected in the hematological and related blood chemistry values from the Australian Imaging Biomarker and Lifestyle (AIBL) study (a community-based, cross-sectional cohort comprising 768 healthy controls (HC), 133 participants with mild cognitive impairment (MCI) and 211 participants with AD). We found that individuals with AD had significantly lower hemoglobin, mean cell hemoglobin concentrations, packed cell volume and higher erythrocyte sedimentation rates (adjusted for age, gender, APOE-ɛ4 and site). In AD, plasma iron, transferrin, transferrin saturation and red cell folate levels exhibited a significant distortion of their customary relationship to hemoglobin levels. There was a strong association between anemia and AD (adjusted odds ratio (OR)=2.43, confidence interval (CI) (1.31, 4.54)). Moreover, AD emerged as a strong risk factor for anemia on step-down regression, even when controlling for all other available explanations for anemia (adjusted OR=3.41, 95% CI (1.68, 6.92)). These data indicated that AD is complicated by anemia, which may itself contribute to cognitive decline.


[Thromboembolic prophylaxis in bariatric surgery. A multidisciplinary protocol].
Severe or morbid obesity is one of the 21st century epidemics. Surgery is the most important and cost-effective treatment. Bariatric procedures are becoming very common in our Hospitals. Thromboembolic events such us deep venous thrombosis or pulmonary embolism (PE) are the most common medical cause of death after these procedures. Incidence of PE may arise to 3% after surgery and its mortality is about 75%. Prophylactic protocols have not been clearly defined until now. These protocols have to consider special patients, such as morbid obese ones; different kind of procedures, most of the laparoscopic; and patients' comorbidities. By the other hand, treatment for morbid obesity has to be considered by a multidisciplinary approach. Here we present the protocol that has been initiated at our Institution. After a long and high experience in bariatric procedures, we have defined a multidisciplinary protocol to prevent thromboembolic events after surgery where nurses and surgeons play a leading role. The combination of physical, pharmaceutical and educational measures all together are the key for the adequate prevention in these patients.


Phytochemicals and antioxidant activity of fruits and leaves of paprika (Capsicum Annuum L., var. special) cultivated in Korea.
The phytochemical composition of carotenoids, tocopherols, free sugars, organic acids, L-ascorbic acid, capsaicinoids, and flavonoids in green and red paprika (GP and RP), and paprika leaves (PL) cultivated in Korea were analyzed. The ethanolic extracts of GP, RP, and PL were obtained with 80% ethanol, and their antioxidative activities were determined by measuring their ABTS and DPPH radical scavenging activities. RP showed the highest contents of capsanthin (58.33 ± 3.91 mg/100 g dry weight) and L-ascorbic acid (1987.25 ± 19.64 mg/100 g dry weight), and main compounds of PL were lutein, chlorophyll, and γ-tocopherol (96.91 ± 14.58, 2136.71 ± 21.11, and 723.49 ± 54.10 mg/100 g dry weight, respectively). RP showed the strongest antioxidant activity (IC(50) = 55.23 ± 6.77 μg/mL in a 2, 2'-azino-di-[3-ethylbenzthiazoline sulphonate] assay and 150.40 ± 8.07 μg/mL in a 2, 2-diphenyl-2-picrylhydrazyl assay), and the antioxidant activity of PL was higher than β-carotene but lower than RP. The results indicate that the amounts of capsanthin and L-ascorbic acid in RP correlate well with antioxidant activity. PL, which has various phytochemicals such as lutein, chlorophyll, and γ-tocopherol, might be used in nutraceuticals and pharmaceuticals for improving human health.


Poor quality of life in patients with urethral stricture treated with intermittent self-dilation.
We assessed patient perceptions of regular intermittent self-dilation in men with urethral stricture. We constructed and distributed a visual analog questionnaire to evaluate intermittent self-dilation via catheterization by men referred for urethral stricture management at a total of 4 institutions. Items assessed included patient duration, frequency, difficulty and pain associated with intermittent self-dilation as well as interference of intermittent self-dilation with daily activity. The primary outcome was patient perceived quality of life. Multivariate analysis was performed to assess factors that affected this outcome. Included in the study were 85 patients with a median age of 68 years, a median of 3.0 years on intermittent self-dilation and a median frequency of 1 dilation per day. On a 1 to 10 scale the median intermittent self-dilation difficulty was 5.0 ± 2.7, the median pain score was 3.0 ± 2.7 and median interference with daily life was 2.0 ± 1.3. Overall quality of life in patients with stricture was poor (median score 7.0 ± 2.6 with poor quality of life defined as 7 or greater). On univariate analysis younger age (p <0.01), interference (p = 0.03), pain (p <0.01) and difficulty performing intermittent self-dilation (p = 0.03) correlated with poor quality of life in a statistically significant manner. On multivariate analysis only difficulty catheterizing (p <0.01) and younger age (p = 0.05) were statistically significant predictors. Patients with stricture involving the posterior urethra had a statistically significant increase in difficulty and decrease in quality of life (each p = 0.04). Most patients with urethral stricture who are on intermittent self-dilation rate difficulty and pain as moderate, and inconvenience as low but report poor quality of life.


Costs and outcomes of phacoemulsification for cataracts performed by residents.
To describe costs and outcomes of phacoemulsification for cataracts performed by ophthalmology residents. We obtained medical records from patients operated on in 2011 by third year residents (R3) using phacoemulsification (n=576). Our expenses estimation included professionals' and hospital costs (fees, materials, medications, and equipment). The study outcomes included spectacle-corrected visual acuities before and six months after the operation, rate of intraoperative complications, and total number of postoperative visits. We compared outcome variables with those from extracapsular cataract extraction procedures (n=274) performed by R3 residents in 1997. The mean total cost for phacoemulsification was US$ 416, while an overall estimation indicated the extracapsular cataract extraction cost at US$ 284 (as of December 30, 2011). The mean preoperative spectacle-corrected visual acuity was worse for eyes scheduled for extracapsular cataract extraction (1.73 ± 0.62), than for eyes scheduled for phacoemulsification (0.74 ± 0.54 logMAR) (p<0.01); the mean postoperative visual acuity was better for phacoemulsification (0.21 ± 0.36 logMAR), than for extracapsular cataract extraction (0.63 ± 0.63 logMAR) (p<0.01). Most patients undergoing phacoemulsification (85%) achieved postoperative spectacle-corrected visual acuities ≥0.30 logMAR, while only 45% of those undergoing extracapsular cataract extractions achieved the same postoperative visual acuity (p<0.01). The rate of intraoperative complications was significantly higher after extracapsular cataract extractions (21%) than it was after phacoemulsifications (7.6%) (p<0.01), and the mean number of postoperative visits was also higher after extracapsular cataract extractions (5.6 ± 2.3) than after phacoemulsifications (4.5 ± 2.4) (p<0.01). These data indicate that cataract surgery performed by in-training ophthalmologists using phacoemulsification is expensive, but compared to extracapsular cataract extraction results, teaching phacoemulsification leads to an approximate three-fold lower complication rate, smaller number of postoperative visits and, most importantly, better visual acuities.


[Organ-saving operations in different localization of breast cancer].
Two methods of filling breast defects after radical resection for nodular cancer located in inner and low quadrants were developed allowing to perform axillary lymphadenectomy without additional axillary approach (patents No. 2125408 and No. 2127552). The methods are based on transposition of breast skin flaps. These methods have been used in 43 patients: in 31 women with T1-2N0 M0 stage, in 12 women T1-2N1-2M0, and with breast size B(2)--in 8, C(3)--in 30, D-E(4-5)--in 5 patients. Flap's marginal necrosis was in 3 patients only. Cosmetic results were excellent and good in 72.1% of operated patients.


G-Box binding factor1 reduces CATALASE2 expression and regulates the onset of leaf senescence in Arabidopsis.
Hydrogen peroxide (H(2)O(2)) is discussed as being a signaling molecule in Arabidopsis (Arabidopsis thaliana) leaf senescence. Intracellular H(2)O(2) levels are controlled by the H(2)O(2)-scavenging enzyme catalase in concert with other scavenging and producing systems. Catalases are encoded by a small gene family, and the expression of all three Arabidopsis catalase genes is regulated in a senescence-associated manner. CATALASE2 (CAT2) expression is down-regulated during bolting time at the onset of leaf senescence and appears to be involved in the elevation of the H(2)O(2) level at this time point. To understand the role of CAT2 in senescence regulation in more detail, we used CAT2 promoter fragments in a yeast one-hybrid screen to isolate upstream regulatory factors. Among others, we could identify G-Box Binding Factor1 (GBF1) as a DNA-binding protein of the CAT2 promoter. Transient overexpression of GBF1 together with a CAT2:beta-glucuronidase construct in tobacco (Nicotiana benthamiana) plants and Arabidopsis protoplasts revealed a negative effect of GBF1 on CAT2 expression. In gbf1 mutant plants, the CAT2 decrease in expression and activity at bolting time and the increase in H(2)O(2) could no longer be observed. Consequently, the onset of leaf senescence and the expression of senescence-associated genes were delayed in gbf1 plants, clearly indicating a regulatory function of GBF1 in leaf senescence, most likely via regulation of the intracellular H(2)O(2) content.


Concept and Evaluation of a New Piezoelectric Transducer for an Implantable Middle Ear Hearing Device.
Implantable middle ear hearing devices (IMEHDs) have been developed as a new technology to overcome the limitations of conventional hearing aids. The piezoelectric cantilever transducers currently used in the IMEHDs have the advantages of low power consumption and ease of fabrication, but generate less high-frequency output. To address this problem, we proposed and designed a new piezoelectric transducer based on a piezoelectric stack for the IMEHD. This new transducer, attached to the incus body with a coupling rod, stimulates the ossicular chain in response to the expansion-and-contraction of its piezoelectric stack. To test its feasibility for hearing loss compensation, a bench testing of the transducer prototype and a temporal bone experiment were conducted, respectively. Bench testing results showed that the new transducer did have a broad frequency bandwidth. Besides, the transducer was found to have a low total harmonic distortion (<0.75%) in all frequencies, and small release time (1 ms). The temporal bone experiment further proved that the transducer has the capability to produce sufficient vibrations to compensate for severe sensorineural hearing loss, especially at high frequencies. This property benefits the treatment of the most common sloping high-frequency sensorineural hearing loss. To produce a 100 dB SPL equivalent sound pressure at 1 kHz, its power consumption is 0.49 mW, which is low enough for the transducer to be utilized in the IMEHD.


Ion currents through Kir potassium channels are gated by anionic lipids.
Ion currents through potassium channels are gated. Constriction of the ion conduction pathway at the inner helix bundle, the textbook gate of Kir potassium channels, has been shown to be an ineffective permeation control, creating a rift in our understanding of how these channels are gated. Here we present evidence that anionic lipids act as interactive response elements sufficient to gate potassium conduction. We demonstrate the limiting barrier to K+ permeation lies within the ion conduction pathway and show that this gate is operated by the fatty acyl tails of lipids that infiltrate the conduction pathway via fenestrations in the walls of the pore. Acyl tails occupying a surface groove extending from the cytosolic interface to the conduction pathway provide a potential means of relaying cellular signals, mediated by anionic lipid head groups bound at the canonical lipid binding site, to the internal gate.


Progression to overweight, obesity and associated factors after antiretroviral therapy initiation among Brazilian persons with HIV/AIDS.
To assess body weight changes, progression to overweight/obesity and investigate the associated factors among HIV/AIDS patients. A retrospective study was conducted involving a sample group of 203 adults with HIV/AIDS. Medical records were used to gather demographic, clinical and anthropometric information. The variables were compared by Chi-square tests, Student's t tests and One-way analysis of variance. The majority of the individuals studied were men (72.4%) with an average age of 34.68 +/- 8.3 years, and time of HIV infection of 4.12 +/- 1.8 years. 63% of the patients gained weight. The greatest weight gain was observed among patients with lower CD4 cell count on admission (8.45 +/- 6.6 vs. 5.97 +/- 4.97) p = 0.019. 39/203 new cases of overweight/obesity were identified, with a progression rate of 19%. Men were more likely to progress to overweight (p < 0.001) and women to obesity (p < 0.001). A direct and significant relationship was observed between the BMI level on admission and being overweight/obese at the end of the study for individuals admitted with normal weight. The results of the study show that in the course of HIV infection overweight/obesity affected men and women admitted with normal weight, although a greater proportion of women progressed to obesity. A higher weight gain contributed in a negative manner to the presence of dyslipidemias in these patients. These data show the importance of monitoring body weight in the course of HIV/AIDS treatment, even in those individuals who present normal body weight.


[Current participation of the nurse in the activities covered in the "expanded role of nursing"].
The article reports on a survey conducted in Colombia to evaluate the part played by the nurse in the functions covered by what has come to be called "the expanded role of nursing." According to the survey, there are 2,213 practicing nurses, who are clustered in the principal cities of the country. Those who participated in the study are young nurses holding staff positions in such institutions as university and social security hospitals. Their training is mostly at the university level, and they have had five years or less of experience. The article notes that, to perform the duties of the expanded role, the nurse must participate in accordance with her training, interest and motivation. The participation may be conditioned by factors in the nurse herself (prior knowledge, former training, previous participation, and responsibility) and by factors in the working environment (the person who instructed her on her role, the post she holds, her length of service/length of her work day, permission received from the institution to exercise her function, and the medical and nursing agreement). Parodoxically, the nurse is being made a participant in new functions at hospitals where there are medical resources and not in regions and places where those resources are scarce or nonexistent. The expanded role of nursing opens to the nurse a range of activities that enable her to provide quality care to the patient and to his or her family and community, to extend the coverage of health services, and offer treatment effectively.


Screening for connective tissue disease in pulmonary arterial hypertension.
To evaluate the utility of anti-nuclear antibody (ANA) levels in distinguishing the cause of pulmonary arterial hypertension as idiopathic (IPAH) or connective tissue disease related (CTD-PAH). We retrospectively identified patients with IPAH or CTD-PAH seen between 2010 and 2012 at our institution. Medical records were reviewed for demographic and clinical data and laboratory values. Of 115 patients identified, 65 (56%) had IPAH and 50 (44%) had CTD-PAH. The mean age was 59 years and most of the patients (76%) were women. Most patients (64%) were in World Health Organization functional class III or IV. Compared with the IPAH group, the CTD-PAH group had significantly increased B-type natriuretic peptide levels (635 vs 325 pg/mL; P = 0.02) and decreased pulmonary vascular resistance (6 vs 9 WU; P = 0.04). The median ANA level was significantly higher in the CTD-PAH group than the IPAH group (7 vs 0 U; P < 0.001). The area under the receiver operating characteristic curve for a positive ANA to predict CTD-PAH was 0.91 (P < 0.001). A cutoff of 5 U for predicting ANA provided an optimal specificity of 94% and a sensitivity of 70%. The resulting likelihood ratio using the same cutoff was 12 (P < 0.001), or a positive predictive value of 91% with a negative predictive value of 79%. In this selected cohort of patients, a quantitative ANA value >5 U may be useful in distinguishing CTD-PAH from IPAH, but a lower level does not confidently exclude CTD-PAH.


Homologous recombination between p53 and its pseudogene in a radiation-induced mouse tumor.
Genome recombination is essential for life; however, its dysfunction causes cancer. Here we report the formation of a chimera structure of the p53 gene due to homologous recombination with the p53 pseudogene in tumors produced by repeated local beta-irradiation of the backs of mice. The recombination occurred near the 5' end of exon 5. Because this tumor carried a 5-bp deletion in exon 6 of the expressed p53 allele, and the defect in p53 is reported to elevate the cellular recombination activity, this chimera formation is thought to be initiated by a radiation-induced DNA double strand break in the p53-mutated cell with enhanced recombination. The abundance of this chimera structure was estimated to be 8% of the total of tumor p53, and the functional p53 side of this chimera had no deletion in exon 6. The indication is that the recombination occurred before the loss of heterozygosity of the mutated p53 allele took place but after a few divisions of the original heterozygous p53-mutated cell toward monoclonal expansion. A novel mechanism of cancer induction is suggested.


Signaling mechanisms that direct cell fate specification and morphogenesis in human embryonic stem cells-based models of human gastrulation.
During mammalian gastrulation, a mass of pluripotent cells surrounded by extraembryonic tissues differentiates into germ layers, mesoderm, endoderm, and ectoderm. The three germ layers are then organized into a body plan with organ rudiments via morphogenetic gastrulation movements of emboly, epiboly, convergence, and extension. Emboly is the most conserved gastrulation movement, whereby mesodermal and endodermal progenitors undergo epithelial-to-mesenchymal transition (EMT) and move via a blastopore/primitive streak beneath the ectoderm. Decades of embryologic, genetic, and molecular studies in invertebrates and vertebrates, delineated a BMP > WNT > NODAL signaling cascade underlying mesoderm and endoderm specification. Advances have been made in the research animals in understanding the cellular and molecular mechanisms underlying gastrulation morphogenesis. In contrast, little is known about human gastrulation, which occurs in utero during the third week of gestation and its investigations face ethical and methodological limitations. This is changing with the unprecedented progress in modeling aspects of human development, using human pluripotent stem cells (hPSCs), including embryonic stem cells (hESC)-based embryo-like models (SCEMs). In one approach, hESCs of various pluripotency are aggregated to self-assemble into structures that resemble pre-implantation or post-implantation embryo-like structures that progress to early gastrulation, and some even reach segmentation and neurulation stages. Another approach entails coaxing hESCs with biochemical signals to generate germ layers and model aspects of gastrulation morphogenesis, such as EMT. Here, we review the recent advances in understanding signaling cascades that direct germ layers specification and the early stages of gastrulation morphogenesis in these models. We discuss outstanding questions, challenges, and opportunities for this promising area of developmental biology.


Gene delivery of sarcoplasmic reticulum calcium ATPase inhibits ventricular remodeling in ischemic mitral regurgitation.
Mitral regurgitation (MR) doubles mortality after myocardial infarction (MI). We have demonstrated that MR worsens remodeling after MI and that early correction reverses remodeling. Sarcoplasmic reticulum Ca(+2)-ATPase (SERCA2a) is downregulated in this process. We hypothesized that upregulating SERCA2a might inhibit remodeling in a surgical model of apical MI (no intrinsic MR) with independent MR-type flow. In 12 sheep, percutaneous gene delivery was performed by using a validated protocol to perfuse both the left anterior descending and circumflex coronary arteries with occlusion of venous drainage. We administered adeno-associated virus 6 (AAV6) carrying SERCA2a under a Cytomegalovirus promoter control in 6 sheep and a reporter gene in 6 controls. After 2 weeks, a standardized apical MI was created, and a shunt was implanted between the left ventricle and left atrium, producing regurgitant fractions of ≈30%. Animals were compared at baseline and 1 and 3 months by 3D echocardiography, Millar hemodynamics, and biopsies. The SERCA2a group had a well-maintained preload-recruitable stroke work at 3 months (decrease by 8±10% vs 42±12% with reporter gene controls; P<0.001). Left ventricular dP/dt followed the same pattern (no change vs 55% decrease; P<0.001). Left ventricular end-systolic volume was lower with SERCA2a (82.6±9.6 vs 99.4±9.7 mL; P=0.03); left ventricular end-diastolic volume, reflecting volume overload, was not significantly different (127.8±6.2 vs 134.3±9.4 mL). SERCA2a sheep showed a 15% rise in antiapoptotic pAkt versus a 30% reduction with the reporter gene (P<0.001). Prohypertrophic activated STAT3 was also 41% higher with SERCA2a than in controls (P<0.001). Proapoptotic activated caspase-3 rose >5-fold during 1 month in both SERCA2a and control animals (P=NS) and decreased by 19% at 3 months, remaining elevated in both groups. In this controlled model, upregulating SERCA2a induced better function and lesser remodeling, with improved contractility, smaller volume, and activation of prohypertrophic/antiapoptotic pathways. Although caspase-3 remained activated in both groups, SERCA2a sheep had increased molecular antiremodeling "tone." We therefore conclude that upregulating SERCA2a inhibits MR-induced post-MI remodeling in this model and thus may constitute a useful approach to reduce the vicious circle of remodeling in ischemic MR.


Mucin 21 confers resistance to apoptosis in an O-glycosylation-dependent manner.
Highly glycosylated mucins protect epithelial surfaces from external insults and are related to malignant behaviors of carcinoma cells. However, the importance of carbohydrate chains on mucins in the process of cellular protection is not fully understood. Here, we investigated the effect of human mucin-21 (MUC21) expression on the susceptibility to apoptosis. MUC21 transfection into HEK293 cells decreased the number of apoptotic cells in culture media containing etoposide or after ultraviolet light irradiation. We used Chinese hamster ovary (CHO) cell variants to investigate the importance of MUC21 glycosylation in the resistance to apoptosis. When MUC21 was expressed in CHO-K1 cells, it was glycosylated with sialyl T-antigen and the cells showed resistance to etoposide-induced apoptosis. MUC21 transfection into Lec2 cells, a variant of CHO cells lacking sialylation of glycans, revealed that the presence of nonsialylated T-antigen also renders cells resistant to etoposide-induced apoptosis. MUC21 was transfected into ldlD cells and the glycosylation was manipulated by supplementation to the medium. Nonsupplemented cells and cells supplemented with N-acetylgalactosamine showed no resistance to etoposide-induced apoptosis. In contrast, these cells supplemented with N-acetylgalactosamine plus galactose expressed sialyl T-antigen and exhibited resistance to etoposide-induced apoptosis. Finally, galectin-3 knockdown in MUC21 transfectants of HEK293 cells did not significantly affect MUC21-dependent induction of apoptosis resistance. The results suggest that T-antigen with or without sialic acid is essential to the antiapoptotic effect of MUC21.


Early Castration in Horses Does Not Impact Osteoarticular Metabolism.
The castration of stallions is traditionally performed after puberty, at around the age of 2 years old. No studies have focused on the effects of early castration on osteoarticular metabolism. Thus, we aimed to compare early castration (3 days after birth) with traditional castration (18 months of age) in horses. Testosterone and estradiol levels were monitored from birth to 33 months in both groups. We quantified the levels of biomarkers of cartilage and bone anabolism (CPII and N-MID) and catabolism (CTX-I and CTX-II), as well as of osteoarthritis (HA and COMP) and inflammation (IL-6 and PGE2). We observed a lack of parallelism between testosterone and estradiol synthesis after birth and during puberty in both groups. The extra-gonadal synthesis of steroids was observed around the 28-month mark, regardless of the castration age. We found the expression of estrogen receptor (ESR1) in cartilage and bone, whereas androgen receptor (AR) expression appeared to be restricted to bone. Nevertheless, with respect to osteoarticular metabolism, steroid hormone deprivation resulting from early castration had no discernable impact on the levels of biomarkers related to bone and cartilage metabolism, nor on those associated with OA and inflammation. Consequently, our research demonstrated that early castration does not disrupt bone and cartilage homeostasis.


Strategies for working across Canadian practice-based research and learning networks (PBRLNs) in primary care: focus on frailty.
Practice based research and learning networks (PBRLNs) are groups of learning communities that focus on improving delivery and quality of care. Accurate data from primary care electronic medical records (EMRs) is crucial in forming the backbone for PBRLNs. The purpose of this work is to: (1) report on descriptive findings from recent frailty work, (2) describe strategies for working across PBRLNs in primary care, and (3) provide lessons learned for engaging PBRLNs. We carried out a participatory based descriptive study that engaged five different PBRLNs. We collected Clinical Frailty Scale scores from a sample of participating physicians within each PBRLN. Descriptive statistics were used to analyze frailty scores and patients' associated risk factors and demographics. We used the Consolidated Framework for Implementation Research to inform thematic analysis of qualitative data (meeting minutes, notes, and conversations with co-investigators of each network) in recognizing challenges of working across networks. One hundred nine physicians participated in collecting CFS scores across the five provinces (n = 5466). Percentages of frail (11-17%) and not frail (82-91%) patients were similar in all networks, except Ontario who had a higher percentage of frail patients (25%). The majority of frail patients were female (65%) and had a significantly higher prevalence of hypertension, dementia, and depression. Frail patients had more prescribed medications and numbers of healthcare encounters. There were several noteworthy challenges experienced throughout the research process related to differences across provinces in the areas of: numbers of stakeholders/staff involved and thus levels of burden, recruitment strategies, data collection strategies, enhancing engagement, and timelines. Lessons learned throughout this multi-jurisdictional work included: the need for continuity in ethics, regular team meetings, enhancing levels of engagement with stakeholders, the need for structural support and recognizing differences in data sharing across provinces. The differences noted across CPCSSN networks in our frailty study highlight the challenges of multi-jurisdictional work across provinces and the need for consistent and collaborative healthcare planning efforts.


Oxidation of trichloroethylene by liver microsomal cytochrome P-450: evidence for chlorine migration in a transition state not involving trichloroethylene oxide.
Trichloroethylene (TCE) was metabolized by cytochrome P-450 containing mixed-function oxidase systems to chloral (2,2,2,-trichloroacetaldehyde), glyoxylic acid, formic acid, CO, and TCE oxide. TCE oxide was synthesized, and its breakdown products were analyzed. Under acidic aqueous conditions the primary products were glyoxylic acid and dichloracetic acid. The primary compounds formed under neutral or basic aqueous conditions were formic acid and CO. TCE oxide did not form chloral in any of these or other aqueous systems, even when iron salts, ferriprotoporphyrin IX, or purified cytochrome P-450 was present. Ferric iron salts catalyzed the rearrangement of TCE oxide to chloral only in CH2Cl2 or CH3CN. A 500-fold excess of iron was required for complete conversion. A kinetic model involving the zero-order oxidation of TCE to TCE oxide by cytochrome P-450 and the first-order degradation of the epoxide was used to test the hypothesis that TCE oxide is an obligate intermediate in the conversion of TCE to other metabolites. Kinetic constants fo the breakdown of TCE oxide and for the oxidative metabolism of TCE to stable metabolites were used to predict epoxide concentrations required to support the obligate intermediacy of TCE oxide. The maximum levels of TCE oxide detected in systems using microsomal fractions and purified cytochrome P-450 were 5-28-fold lower than those predicted from the model. The kinetic data and the discrepancies between the observed metabolites and TCE oxide breakdown products support the view that the epoxide is not an obligate intermediate in the formation of chloral, and an alternative model is presented in which chlorine migration occurs in an oxygenated TCE-cytochrome P-450 transition state.


The association between tobacco or nicotine product use behaviors and non-compliance with mask-wearing during the COVID-19 pandemic: a cross-sectional study in Korea.
It is necessary to investigate tobacco or nicotine product (TNP) use which acts as a risk factor for coronavirus disease 2019 (COVID-19) infection. Especially, wearing a mask is difficult to practice while using TNP. Therefore, this study aimed to examine the association between TNP use behaviors and non-compliance with mask-wearing during the COVID-19 pandemic. The samples of 208,618 Korean adults from 2020 Community Health Survey in Korea were used. As an independent variable, TNP use behaviors such as TNP use status, changes in TNP use after the COVID-19 outbreak, TNP types, and attempt to quit were analyzed. Logistic regression was performed on gender-stratified participants. Among men, the odds ratio (OR) of current and former TNP users were 2.00 (95% confidence interval [CI], 1.66 to 2.40) and 1.32 (95% CI, 1.09 to 1.60), respectively, compared to never users. In women, OR was 1.50 (95% CI, 1.00 to 2.26) for former users. Cigarette use was more associated with not wearing a mask than non-cigarette tobacco or nicotine product (NCTNP) use (OR, 1.53; 95% CI, 1.12 to 2.08). Men whose TNP use decreased had lower non-compliance (OR, 0.52; 95% CI, 0.36 to 0.74); while women whose TNP use increased had lower non-compliance (OR, 0.13; 95% CI, 0.07 to 0.26). Current and former users were less likely to wear masks. Cigarette use was more associated with not wearing a mask than NCTNP use. Changes in TNP use showed association for men and women; however, in the opposite direction. Therefore, more attention should be paid to TNP use prevention and cessation support during the epidemic of respiratory infectious diseases. Moreover, it is necessary to identify risk factors of cigarette users in compliance with mask-wearing.


Predicting outcome by growth rate of locally recurrent retroperitoneal liposarcoma: the one centimeter per month rule.
To identify the prognostic variables that predict disease-specific survival and second local recurrence-free survival in patients with recurrent retroperitoneal liposarcoma so as to guide clinical management. Local recurrence after complete resection of primary retroperitoneal liposarcoma is a common clinical problem that frequently leads to morbidity and mortality. Factors that determine survival in patients with a local recurrence after complete resection of the primary and rerecurrence after resection of the first local recurrence have not been clearly defined. From a prospective sarcoma database we selected 105 patients who had at least one local recurrence following complete resection of a primary retroperitoneal liposarcoma between July 1982 and December 2005. Of these patients, 61 underwent complete resection of their first local recurrence. Study endpoints included second local recurrence-free survival for these 61 patients and disease-specific survival for all 105 patients. Univariate analysis was performed with the Kaplan-Meier method and log-rank test, and multivariate analysis with the Cox proportional hazards model and score test. Local recurrence growth rate was defined as the radiographic size of the local recurrence divided by the time to local recurrence from the primary resection. Median follow-up was 65 months. Local recurrence size, primary histologic variant and grade, and local recurrence growth rate were independent predictors of disease-specific survival. For those undergoing reresection, local recurrence size and local recurrence growth rate independently influenced development of a second local recurrence. Only patients with local recurrence growth rates of less than 0.9 cm/mo were associated with improved survival after aggressive resection of the local recurrence. Local recurrence growth rate is strongly associated with disease-specific survival and local control for patients with completely resected locally recurrent retroperitoneal liposarcoma. Despite aggressive operative management patients with a local recurrence growth rate greater than 0.9 cm/mo were associated with poor outcomes and should be considered for enrollment in clinical trials employing novel agents.


Specialists' approach to tracheal collapse: survey-based opinions on diagnostics, medical management, and comorbid diseases.
To describe the current standard of care among specialists for the routine diagnostic evaluation and medical management of stable tracheal collapse in dogs, identifying gaps between practice and scientific evidence to facilitate the development of future prospective studies. A secondary objective was to describe the perceived incidence of selected comorbid disorders in dogs with tracheal collapse and the diagnostic tests performed to evaluate for those disorders. 180 veterinary specialists in 22 countries. An electronic survey was sent to 4 specialty listservs to target diplomates. Respondents completed multiple-choice and free-response questions related to the diagnostic evaluation and treatment of a theoretical stable dog with suspected tracheal collapse. Most respondents routinely utilized radiography, tracheobronchoscopy, and fluoroscopy to diagnose tracheal collapse and performed airway sampling, sedated airway examination, and echocardiograms to rule out comorbidities. The most frequently perceived comorbid disorders included chronic bronchitis, bronchomalacia, and myxomatous mitral valve disease. Respondents most often prescribed opioid antitussives, glucocorticoids, anxiolytics, and antibiotics as treatments. Less frequently, they utilized bronchodilators and nonopioid medications for cough. Despite a lack of published guidelines, specialists have similar approaches in their diagnostic and therapeutic approach to a stable dog with suspected tracheal collapse and believe evaluating for comorbid disorders is important. A description of a typical diagnostic approach and knowledge of realistic treatment goals will assist the general practitioner managing dogs with stable tracheal collapse. Additionally, gaps between current practices established via this survey and data supporting those practices exist, specifically concerning the use of antibiotics and nonopioid medications for cough, representing areas for further study.


Is low molecular weight heparin a neuroprotectant?
This communication reports the results of investigations on the effect of low molecular weight heparin (LMWH) on intraneuronal calcium release, and considers its possible relevance to the treatment of ischemic stroke. It previously was shown that intraneuronal injection of conventional heparin (MW 12,000) in vitro prevents glutamate-induced calcium release from intracellular stores through its blocking action on IP3 (inositol-1,4,5-triphosphate) receptors, and thus interferes with events occurring in the ischemic cascade. In the experiments reported herein, a LMWH of MW 4500 was shown to have these same effects when injected into a Purkinje cell in an in vitro cerebellar slice preparation, and also when administered externally (bath application). By contrast, conventional heparin works only when injected into the cell; bath application has no effect. The results are interpreted to mean that the larger conventional heparin molecule cannot pass through the cell membrane, while the smaller LMWH molecule does indeed enter the cell. In a clinical trial, LMWH begun within 48 hours of ischemic stroke onset in humans improved outcome at 6 months; conventional heparin given in a similar trial was without benefit. That one anticoagulant was beneficial while another failed suggests the possibility that the difference was independent of effect on the clotting system. The experimental data herein reported support the view that LMWH may benefit stroke victims by an action directly cytoprotective against the consequences of neuronal ischemia.


Physical exercise during pregnancy minimizes PTZ-induced behavioral manifestations in prenatally stressed offspring.
Stress during gestation has been shown to affect susceptibility and intensity of seizures in offspring. Environmental stimuli, such as maternal physical exercise, have shown to be beneficial for brain development. Although studies have demonstrated the deleterious influence of stress during pregnancy on seizure manifestation in offspring, very little is known on how to minimize these effects. This study verified whether physical exercise during the pregnancy associated with prenatal stress minimizes seizure susceptibility in offspring at the beginning of postnatal development. Pregnant rats and male pups were divided into the following groups: control, stress, stress/forced exercise, and stress/voluntary exercise. Behavioral manifestations were analyzed after injection of pentylenetetrazol (PTZ; 45 and 60 mg/kg) at ages P15 and P25. Increased behavioral manifestations and seizure severity was observed in the stress group compared with the control group at both ages. At the dose of 45 mg/kg, offspring of stressed mothers who performed both physical exercise models showed an increase in latency for the first manifestation and decrease in the seizures severity at both ages compared with the mothers groups who were only stressed. Prenatal restraint stress potentiated PTZ-induced seizure behavior, and both forced and voluntary exercise during gestation attenuates the negative effects of PTZ-induced offspring.


Resistance to adriamycin cytotoxicity among respiratory-deficient mutants in yeast.
Saccharomyces cell uptake of Adriamycin and the ensuing cytotoxic response were found to be dependent upon the ionic strength of the medium used for drug treatment. A given concentration of Adriamycin which inhibited growth in complete medium ws found to be significantly cytotoxic when administered in water. Many survivors after Adriamycin treatment in water were found to be respiratory-deficient petite mutants containing mitochondrial deoxyribonucleic acid mutations. Petite mutants arising after Adriamycin treatment were not induced but selected from the preexisting population of spontaneously derived petite mutants (normal frequency, 2%) due to an increased resistance of these mutants to killing by Adriamycin as compared with normal respiratory-sufficient cells. The responses to Adriamycin in mitochondrial deoxyribonucleic acid respiratory-deficient mutants (rho-, rho degrees, mit-) with different impaired mitochondrial functions was studied. All were similarly more resistant to killing by Adriamycin than wild-type cells. The common deficiency shared by these mutants, i.e., nonfunctioning electron transport, may play a role in protecting these mutants from Adriamycin cytotoxicity. In addition, normal cells grown on glycerol, requiring aerobic respiration for carbon source utilization were more susceptible to killing by Adriamycin than cells grown on glucose. These studies suggest that a mitochndrial function in yeast may interact with Adriamycin to potentiate a cell cytotoxic mechanism of the drug.


Meeting the health information needs of prostate cancer patients using personal health records.
There is interest in the use of health information technology in the form of personal health record (phr) systems to support patient needs for health information, care, and decision-making, particularly for patients with distressing, chronic diseases such as prostate cancer (pca). We sought feedback from pca patients who used a phr. For 6 months, 22 pca patients in various phases of care at the BC Cancer Agency (bcca) were given access to a secure Web-based phr called provider, which they could use to view their medical records and use a set of support tools. Feedback was obtained using an end-of-study survey on usability, satisfaction, and concerns with provider. Site activity was recorded to assess usage patterns. Of the 17 patients who completed the study, 29% encountered some minor difficulties using provider. No security breaches were known to have occurred. The two most commonly accessed medical records were laboratory test results and transcribed doctor's notes. Of survey respondents, 94% were satisfied with the access to their medical records, 65% said that provider helped to answer their questions, 77% felt that their privacy and confidentiality were preserved, 65% felt that using provider helped them to communicate better with their physicians, 83% found new and useful information that they would not have received by talking to their health care providers, and 88% said that they would continue to use provider. Our results support the notion that phrs can provide cancer patients with timely access to their medical records and health information, and can assist in communication with health care providers, in knowledge generation, and in patient empowerment.


Atrial Ablation Lesion Evaluation by Cardiac Magnetic Resonance: Review of Imaging Strategies and Histological Correlations.
Cardiac magnetic resonance (CMR) imaging is a valuable noninvasive tool for evaluating tissue response following catheter ablation of atrial tissue. This review provides an overview of the contemporary CMR strategies to visualize atrial ablation lesions in both the acute and chronic postablation stages, focusing on their strengths and limitations. Moreover, the accuracy of CMR imaging in comparison to atrial lesion histology is discussed. T2-weighted CMR imaging is sensitive to edema and tends to overestimate lesion size in the acute stage after ablation. Noncontrast agent-enhanced T1-weighted CMR imaging has the potential to provide more accurate assessment of lesions in the acute stage but may not be as effective in the chronic stage. Late gadolinium enhancement imaging can be used to detect chronic atrial scarring, which may inform repeat ablation strategies. Moreover, novel imaging strategies are being developed, but their efficacy in characterizing atrial lesions is yet to be determined. Overall, CMR imaging has the potential to provide virtual histology that aids in evaluating the efficacy and safety of catheter ablation and monitoring of postprocedural myocardial changes. However, technical factors, scanning during arrhythmia, and transmurality assessment pose challenges. Therefore, further research is needed to develop CMR strategies to visualize the ablation lesion maturation process more effectively.


Associations between the sexual behaviour of men who have sex with men and the structure and composition of their social networks.
This exploratory study identified associations between the number of sexual partners reported by men who have sex with men (MSM) and the structure and composition of their social networks. A cross sectional survey was conducted of men recruited as key informants, through advertising and chain referral. A face to face interview was conducted with 206 MSM. The interview included information on the number of sexual partners in the previous year and sociodemographic and behavioural characteristics of the participant. Social networks were enumerated and network size and density were calculated. Ordered logistic regression was used to assess the associations between number of sexual partners and personal and network characteristics. The number of anal sex partners reported was higher if the participant had injected drugs in the past year rather than never having injected (odds ratio, 95% confidence interval: 3.23, 1.28 to 8.15), decreased with network density (0.014, 0.002 to 0.008) and increased if the network did not comprise only HIV negative people (1.77, 1.05 to 2.99). The number of additional oral sex partners increased with network size (1.06, 1.02 to 1.10) and decreased with increased network density (0.034, 0.006 to 0.205). In addition to similar effects of network size (1.05, 1.01 to 1.09) and network density (0.086, 0.013 to 0.563) the model for the number of additional manual sex partners also included age (1.03, 1.01 to 1.05). The density of the social networks of MSM appears strongly and consistently associated with patterns of sexual behaviour. This underlines the importance of using network approaches to understanding the sexual behaviour of MSM and their potential value in identifying novel strategies for intervention.


Cyclosporine A alleviates colitis by inhibiting the formation of neutrophil extracellular traps via the regulating pentose phosphate pathway.
The aberrant formation of neutrophil extracellular traps (NETs) has been implicated in ulcerative colitis (UC), a chronic recurrent intestinal inflammation. Cyclosporine A (CsA) is now applied as rescue therapy for acute severe UC. In addition, it has been certained that CsA inhibits the formation of NETs in vitro and the mechanism of which was still vague. The study aimed to explore the mechanism CsA inhibits the NETs formation of colitis in vivo and in vitro. NETs enrichment in clinical samples was analyzed using databases from Gene Expression Omnibus and verified in our center. Dextran sulfate sodium (DSS)-induced acute colitis mice model was used to investigate the effect of CsA on NETs of colonic tissue expression. To clarify the mechanism, intracellular energy metabolites were examined by Liquid Chromatograph Mass Spectrometer, and reactive oxygen species (ROS) levels were examined by fluorescence intensity in neutrophils treated with CsA after LPS stimulation. The transcriptional level and activity of G6PD of neutrophils were also assessed using qRT-PCR and WST-8. RNA Sequencing was used to detect differentially expressed genes of neutrophils stimulated by LPS with or without CsA. The expression levels of related proteins were detected by western blot. NETs enrichment was especially elevated in moderate-to-severe UC patients compared to HC. NETs expression in the colon from DSS colitis was decreased after CsA treatment. Compared with neutrophils stimulated by LPS, NETs formation and cellular ROS levels were decreased in LPS + CsA group. Cellular ribulose 5-phosphate and NADPH/NADP + related to the pentose phosphate pathway (PPP) were reduced in LPS + CsA group. In addition, CsA could decrease G6PD activity in neutrophils stimulated with LPS, and the results were further verified by inhibiting G6PD activity. At last, P53 protein was highly expressed in LPS + CsA group compared with the LPS group. Intracellular G6PD activity, ROS level and NETs formation, which were downregulated by CsA, could be reversed by a P53 inhibitor. Our results indicated CsA could alleviate the severity of colitis by decreasing the formation of NETs in vivo. In vitro, CsA reduced ROS-dependent NETs release via downregulating PPP and cellular ROS levels by decreasing G6PD activity directly by activating the P53 protein.


Evaluation and Management of Primary Hyperparathyroidism: Summary Statement and Guidelines from the Fifth International Workshop.
The last international guidelines on the evaluation and management of primary hyperparathyroidism (PHPT) were published in 2014. Research since that time has led to new insights into epidemiology, pathophysiology, diagnosis, measurements, genetics, outcomes, presentations, new imaging modalities, target and other organ systems, pregnancy, evaluation, and management. Advances in all these areas are demonstrated by the reference list in which the majority of listings were published after the last set of guidelines. It was thus, timely to convene an international group of over 50 experts to review these advances in our knowledge. Four Task Forces considered: 1. Epidemiology, Pathophysiology, and Genetics; 2. Classical and Nonclassical Features; 3. Surgical Aspects; and 4. Management. For Task Force 4 on the Management of PHPT, Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology addressed surgical management of asymptomatic PHPT and non-surgical medical management of PHPT. The findings of this systematic review that applied GRADE methods to randomized trials are published as part of this series. Task Force 4 also reviewed a much larger body of new knowledge from observations studies that did not specifically fit the criteria of GRADE methodology. The full reports of these 4 Task Forces immediately follow this summary statement. Distilling the essence of all deliberations of all Task Force reports and Methodological reviews, we offer, in this summary statement, evidence-based recommendations and guidelines for the evaluation and management of PHPT. Different from the conclusions of the last workshop, these deliberations have led to revisions of renal guidelines and more evidence for the other recommendations. The accompanying papers present an in-depth discussion of topics summarized in this report. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).


Biocompatibility of antimicrobial melimine lenses: rabbit and human studies.
Covalent immobilization of antimicrobial peptide melimine onto contact lenses can produce broad-spectrum antimicrobial lenses. The purpose of this study was to investigate the performance of melimine-coated contact lenses in an animal model and human clinical trial. Melimine was covalently attached onto the surface of contact lenses via EDC (1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride) coupling. A rabbit model of daily contralateral wear of lenses for 22 days was conducted to assess the lens safety. A prospective, randomized, double-masked, one-day human clinical trial was used to evaluate subjective responses and ocular physiology during contralateral wear of melimine-coated (test) and uncoated (control) lenses. Delayed reactions were monitored during follow-up visits after 1 and 4 weeks. Ex vivo retention of antimicrobial activity of worn lenses was assessed by reduction in numbers of viable Pseudomonas aeruginosa and Staphylococcus aureus. Melimine-coated lenses produced no ocular signs or symptoms that would indicate cytotoxicity during the lens wear of rabbits. No histological changes were found in rabbit corneas. During the human trial, no differences were observed in wettability, surface deposition, lens-fitting centration, movement, tightness, and corneal coverage between test and control lenses (p > 0.05). There were no significant differences in bulbar, limbal, or palpebral redness or conjunctival staining (p > 0.05). Mean corneal (extent, depth, and type) staining was higher for test lenses compared with that for control lenses (p < 0.05). There was no significant difference in subjective responses for lens comfort, dryness, and awareness (p > 0.05). No delayed reactions were associated with the test lenses. Worn test lenses retained more than 1.5 log inhibition against both bacterial types. Melimine-coated contact lenses were worn safely by humans. However, they were associated with higher corneal staining. The melimine-coated lenses retained high antibacterial activity after wear.


[Expectations and service performance of social psychiatry services in free Saxony. An analysis of viewpoints of psychiatric practice and clinical specialists and coworkers of social psychiatric services].
After the "Polyclinic system" that had predominated in the GDR had been dismantled, a far-reaching restructuring of the complementary psychiatric care sector became necessary. In the State of Saxony, comprehensive establishment of a homogeneous home-visit outpatient service is the first building block in an interlinked system of regionalized community psychiatry. Based on about 20 years of experience in the Federal States of the FRG, this function is fulfilled by social psychiatry services (SPS). The present study investigates the expectations of free-practising psychiatrists (n = 165), doctors in psychiatric hospitals (n = 95) and staff of social psychiatry services (n = 138) throughout the State of Saxony in respect of available care and the way these new care structures work. The results are approximately representative owing to the high rate of responses in an anonymous postal survey of three specified groups (48.5%, 67.4%, 84.0%). All the groups surveyed expected that the clientel to be looked after by SPS will chiefly consist of the group of chronically mentally ill persons. Moreover, the consistently expressed expectations as to the central care/therapy to be provided by SPS can be summarised as the core of directly client-oriented SPS work. This consists of the elements "welfare work", "individual and institutionalised social therapy", and "help in administrative measures". The main differences between the two groups of doctors is that free-practising psychiatrists more often expect a large SPS involvement with regard to social therapy provided at an institutional level, whereas hospital doctors expect this with regard to medical therapies in the strict sense. Hospital doctors have greater expectations that SPS will also fulfil further functions: work with relatives, public relations, establishment of a crisis service and running self-help groups. The expectations of SPS staff with regard to the therapy they should provide themselves exceed what has already been currently achieved in all sectors. A detailed analysis of contents is also presented in this article. Besides improved staffing, SPS employees state that eliminating internal organisational and postgraduate training deficits are two major requirements for stabilization of their work. Appraisals of the quality of care for the chronically mentally ill in the outpatient complementary sector requested by hospital doctors and SPS staff in comparison with former provision structures in the GDR, show deterioration in the economic security of patients as well as of possibilities available in occupational rehabilitation. On the other hand, there are some improvements in the training of specialist staff whereas protection of the personality rights of patients as well as care measures are now free from ideological bias. These are crucial prerequisites for an update individualised, need-orientated therapeutic procedure. To counteract overburdening of the SPS with expectations of care and to enable a more unequivocal positioning of its structure in a complex system of psychosocial care, further need-orientated development and establishment of psychiatric facilities close to the community concerned, are urgently required, a least as far as the State of Saxony is concerned.


Heat, safety or solitude? Using habitat selection experiments to identify a lizard's priorities.
Laboratory experiments with a rock-dwelling nocturnal gecko, Oedura lesueurii, showed that retreat-site selection (and other behaviours) are affected by the interplay between thermal benefits, social advantages and avoidance of predators. Velvet geckos were highly selective in habitat choice: they preferred artificial retreat-sites that mimic the thermal properties of natural rocks in full sun rather than those that mimic rocks in full shade; mature male geckos rarely shared retreat-sites with other adult males; and these lizards strongly avoided retreat-sites covered with the scent of a natural predator (the broadheaded snake, Hoplocephalus bungaroides). After documenting these preferences, we carried out additional trials in which two or more of these factors co-occurred, as is often the case in nature. Social dominance interacted with thermal benefits in determining retreat-site selection, with smaller (subordinate) males forced to use cooler retreat-sites when larger (dominant) males were present. Avoidance of predators was a higher priority than thermoregulation: the lizards would forego a warmer retreat-site with predator scent in favour of a cooler, unscented one. There was also an interplay between social dominance and predator scent: smaller males were forced to use either predator-scented retreat-sites or no retreat-site when larger males were present. General activity levels, and the frequencies of specific behavioural acts, also shifted in response to social and predator-scent cues. Our study emphasizes the complexity of habitat-selection behaviour in these lizards, and clarifies the criteria used in retreat-site selection when (as is commonly the case) the animal must choose between conflicting priorities. Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.


A novel dominant negative mutation of OTX2 associated with combined pituitary hormone deficiency.
Combined pituitary hormone deficiency (CPHD) is characterized by deficiencies in more than one anterior pituitary hormone. Mutations in developmental factors responsible for pituitary cell specification and gene expression have been found in CPHD patients. OTX2, a bicoid class homeodomain protein, is necessary for both forebrain development and transactivation of the HESX1 promoter, but as of yet, has not been associated with CPHD. The goal of this study was to identify and characterize novel mutations in pituitary specific transcription factors from CPHD patients. Genomic DNA was isolated from patients with hypopituitarism to amplify and sequence eight pituitary specific transcription factors (HESX1, LHX3, LHX4, OTX2, PITX2, POU1F1, PROP1, and SIX6). Characterization of novel mutations is based on structural and functional studies. We describe two unrelated children with CPHD who presented with neonatal hypoglycemia, and deficiencies of GH, TSH, LH, FSH, and ACTH. Magnetic resonance imaging revealed anterior pituitary hypoplasia with an ectopic posterior pituitary. A novel heterozygous OTX2 mutation (N233S) was identified. Wild-type and mutant OTX2 proteins bind equivalently to bicoid binding sites, whereas mutant OTX2 revealed decreased transactivation. A novel mutation in OTX2 binds normally to target genes and acts as a dominant negative inhibitor of HESX1 gene expression. This suggests that the expression of HESX1, required for spaciotemporal development of anterior pituitary cell types, when disrupted, results in an absent or underdeveloped anterior pituitary with diminished hormonal expression. These results demonstrate a novel mechanism for CPHD and extend our knowledge of the spectrum of gene mutations causing CPHD.


Tuning self-motion perception in virtual reality with visual illusions.
Motion perception in immersive virtual environments significantly differs from the real world. For example, previous work has shown that users tend to underestimate travel distances in virtual environments (VEs). As a solution to this problem, researchers proposed to scale the mapped virtual camera motion relative to the tracked real-world movement of a user until real and virtual motion are perceived as equal, i.e., real-world movements could be mapped with a larger gain to the VE in order to compensate for the underestimation. However, introducing discrepancies between real and virtual motion can become a problem, in particular, due to misalignments of both worlds and distorted space cognition. In this paper, we describe a different approach that introduces apparent self-motion illusions by manipulating optic flow fields during movements in VEs. These manipulations can affect self-motion perception in VEs, but omit a quantitative discrepancy between real and virtual motions. In particular, we consider to which regions of the virtual view these apparent self-motion illusions can be applied, i.e., the ground plane or peripheral vision. Therefore, we introduce four illusions and show in experiments that optic flow manipulation can significantly affect users' self-motion judgments. Furthermore, we show that with such manipulations of optic flow fields the underestimation of travel distances can be compensated.


Fabrication of titanium based MALDI bacterial chips for rapid, sensitive and direct analysis of pathogenic bacteria.
For the first time, we report the fabrication of a titanium bacterial chip for MALDI-MS produced from a simple, cost effective and rapid heat treatment process. This bacterial chip can be reused many times and is highly versatile. These bacterial chips serve dual roles: (1) They can be applied as MALDI-MS target plates for direct and highly sensitive bacterial analysis. (2) They can be used as bacterial sensors for direct analysis of the captured bacteria using MALDI-MS. The sensitivity of these chips when used as bacterial sensors is <10(3)cfu/mL. The lowest detectable concentration for direct MALDI-MS analysis was found to be 10(4)cfu/mL. The results were further justified by using standard plate counting method combined with Tukey-Kramer statistical analysis and fluorescence imaging followed by image processing for fluorescence quantification using ImageJ software to substantiate the MALDI-MS results.


Hepatic metastatic thymoma and myasthenia gravis twenty-two years after the apparent cure of an invasive thymoma. A case report and review of the literature.
We report the case of a 62-year-old woman who presented in myasthenic crisis 22 years after radiation- and chemotherapy of an invasive thymoma which occurred during pregnancy. There was no evidence of recurrence of the thymoma at its original site, but an isolated hepatic metastasis was discovered. Biopsy of the mass revealed a spindle cell thymoma, whereas the original histology was that of a mixed round and spindle cell thymoma with moderate lymphocytic infiltration. The patient expired in spite of treatment with steroids, pyridostigmine bromide and plasma exchange on the one hand and cyclophosphamide with adriamycin on the other. To our knowledge, 22 years is the longest reported interval for the appearance of metastatic thymoma and myasthenia gravis after the diagnosis and apparent cure of a primary thymoma. This is also the only reported case of thymoma occurring during pregnancy but not associated with a rapidly fatal outcome.


Stakeholder Use and Feedback on Vaccination History and Clinical Decision Support for Immunizations Offered by Public Health.
National initiatives on Electronic Health Records (EHRs) recognize the vital role of public health and recommend reporting to Immunization Information Systems (IIS) and access of its clinical decision support for immunizations (CDSi). The objective of this study was to collect stakeholder feedback on access and utilization of CDSi from the Minnesota Immunization Information Connection (MIIC), Minnesota's IIS. Input was solicited using a semi-structured questionnaire developed by experts, and from a sample of 17 key informants from February 2015 through May 2016. Analysis highlighted the appreciation of MIIC services, comprehensive vaccination history across providers and CDSi functionality, with public health users relying on MIIC. It also identified issues such as data entry due to read-only view, data quality and communications for improvement. These findings underscore the critical role of IIS, need to engage stakeholders, ensure CDSi updates, maintain good data quality, and promote bi-directional data exchanges across EHRs-IIS.


Sensitivity and specificity of the histamine challenge test for the diagnosis of asthma in an unselected sample of children and adolescents.
The purpose of this investigation was to study factors of importance for the degree of bronchial responsiveness and, furthermore, to evaluate the sensitivity, specificity and predictive value of a bronchial challenge test with histamine for the diagnosis of asthma in 495 randomly selected children and adolescents, aged 7-16 yrs, from Copenhagen, Rigshospitalet. Detailed history about allergic symptoms, physical examination and bronchial histamine challenge tests were performed at the out-patient clinic. Asthma, atopic disease and height were found to be of great importance for the degree of bronchial responsiveness, whereas the age, sex and smoking habits were of no significance. The percentage of asthmatics with bronchial hyperresponsiveness, i.e. sensitivity to the test, increased towards 100% on inhaling increasing concentrations of histamine, but this was accompanied by a decrease in specificity and predictive values of positive test in regard to the diagnosis of asthma. However, lower concentrations of histamine may be preferable in order to distinguish between asthma and non-asthma in population samples, as inhalation of 2.4 mg.ml-1 and provocative concentration producing a 20% fall in forced expiratory volume in one second (FEV1) (PC20) provided an acceptable sensitivity (57%), specificity (98%), and predictive value of a positive test (60%). We conclude that as regards the diagnosis of asthma, a low predictive value confirms that the bronchial challenge test plays only a supplementary, but valuable, role in detecting the disease in population samples.


Immunosuppression-state-of-the-art: anything new in the pipeline?
Cardiac transplantation has been the therapy for advanced heart failure that is associated with the best and most durable outcomes. This has been a result of improvements in immunosuppression, specifically the widespread adoption of more potent immunosuppressive agents such as tacrolimus and mycophenolate mofetil in place of cyclosporine and azathioprine and more protocol-driven immunosuppressive regimens which minimize both rejection and complications of immunosuppression such as infections and nephrotoxicity. The rejection rates have fallen over the past 2 decades as posttransplant survival has improved. Despite these successes, long-term survival is limited by cardiac allograft vasculopathy and malignancies. The purpose of this review is to discuss new approaches to immunosuppression, which may address the long-term outcomes after transplant. Recent findings in clinical trials have shown that proliferation signal inhibitors or mammalian target of rapamycin inhibitors can reduce the incidence and severity of cardiac allograft vasculopathy and are used in higher doses as anticancer agents, but their uses are associated with side-effects. Consequently, there is considerable interest in developing newer immunosuppressive agents that will be more effective in treating and preventing these long-term complications with fewer side-effects. At present, there are no new agents other than Rituximab, which are being studied, in clinical trials.


Por Nuestros Ojos: understanding social determinants of health through the eyes of youth.
Understanding the social determinants underlying health disparities benefits from a mixed-methods, participatory research approach. Photovoice was used in a research project seeking to identify and validate existing data and models used to address socio-spatial determinants of health in at-risk neighborhoods. High-risk neighborhoods were identified using geospatial models of pre-identified social determinants of health. Students living within these neighborhoods were trained in Photovoice, and asked to take pictures of elements that influence their neighborhood's health and to create narratives explaining the photographs. Students took 300 photographs showing elements that they perceived affected community health. Negative factors included poor pedestrian access, inadequate property maintenance, pollution, and evidence of gangs, criminal activity, and vagrancy. Positive features included public service infrastructure and outdoor recreation. Photovoice data confirmed and contextualized the geospatial models while building community awareness and capacity. Photovoice can be a useful research tool for building community capacity and validating quantitative data describing social determinants of health.