Antisense oligonucleotides to p53 tumor suppressor suppress the induction of apoptosis by epidermal growth factor in NCI-H 596 human lung cancer cells.
Apoptosis has become a basic tool in developing cancer research and establishing new cancer strategies. However, the molecular mechanism of apoptosis is not well understood. Recently, the authors found that epidermal growth factor (EGF) induces apoptosis in various cancer cells and that there is a novel signal pathway mediated through p53 in signal transduction of EGF. The effect of antisense gene therapy to p53 tumor suppressor on EGF-dependent apoptosis was investigated in cultured NCI-H 596 human non-small cell lung cancer cells with a wild-type p53 gene. Results showed that EGF plus p53 sense oligonucleotides induced EGF-dependent and p53-dependent apoptosis in NCI-H 596 cells within 8 hours. On the other hand, antisense gene therapy using antisense oligonucleotides to p53 tumor suppressor suppressed the induction of EGF-dependent and p53-dependent apoptosis. Mutated p53 antisense-containing mutated CG dinucleotides had the same effect as that of p53 antisense on suppression of apoptosis in NCI-H 596 cells. We found that a new nucleic acid drug, another mutated p53 antisense-containing mutation at three bases immediately 5' and 3' from the CG dinucleotides, potentiated the induction of apoptosis and failed to suppress the induction of EGF-dependent apoptosis. These results suggest that gene therapy using antisense oligonucleotides to the p53 tumor suppressor is effective on EGF-dependent apoptosis of NCI-H 596 human non-small cell lung cancer.


The effects of soy extract on the uterus of castrated adult rats.
The aim of this study was to evaluate the effects of different doses of a standardized soy extract on the uterus of castrated rats. Fifty-six adult castrated female Wistar rats were randomly divided into seven groups (eight animals in each) that received: GI--drug vehicle (propylene glycol); GII--soy extract 10mg/kg per day; GIII--soy extract 50mg/kg per day; GIV--soy extract 100mg/kg per day; GV--soy extract 300mg/kg per day; GVI--soy extract 600mg/kg per day; GVII-conjugated equine estrogens (CEE) 200microg/kg per day. After 21 days of treatment, all animals were sacrificed and fragments of the uterine horns were immediately removed, fixed in 10% formaldehyde and submitted to routine histological techniques for morphometric study. The endometrial cell proliferation index was determined with the PCNA antibody PC-10 and expressed as the percentuals of the PCNA-positive nuclei relative to the total countings. Other fragments were immediately frozen in liquid nitrogen for RNA extraction and VEGF analysis using RT-PCR technique. The minimal dose of soy extract that produced a significant increase of the morphometric parameters was 100mg/kg (GIV). The maximum effects on endometrial and myometrial morphometry were detected in the groups treated with 300 and 600mg/kg of soy extract (groups V and VI) and CEE (GVII). The expression of PCNA in the endometrial epithelium and stroma was increased by treatment with 100-600mg/kg per day of soy extract (groups IV-VI) or with CCE (group VII). Doses equal to or higher than 50mg/kg of soy extract (groups III-VI) and CEE stimulated the expression of VEGF. The treatment of adult castrated rats during 21 days with doses of 100mg/kg per day or higher of soy extract may determine significant proliferation in the endometrium and myometrium.


Pediatric Diving-Related Injuries in Swimming Pools Presenting to US Emergency Departments: 2008-2020.
Recreational swimming/diving is among the most common physical activities in US children and a significant cause of morbidity across the United States. This study updates the national epidemiology of diving-related injuries. The Consumer Product Safety Commission's National Electronic Injury Surveillance System database was queried for patients aged 0 to 19 from 2008 to 2020 who presented to any of the 100 National Electronic Injury Surveillance System-participating emergency departments for a diving-related injury. Dive characteristics such as dive height, dive skill, dive direction, and dive sequence were determined from case narratives. A total of 1202 cases were identified for analysis corresponding to a total national estimate of 37,387 diving related injuries during the period from 2008 to 2020 and a national incidence of 3.6 injuries per 100,000 population. Males accounted for 64% of injuries. The average yearly incidences of injury in the 10 to 14 and 15 to 19 age groups were identical at 5.8 per 100,000. Contact with the diving board or platform was the most common cause of injury (34%). Diving backwards or attempting a flip or handstand dive were associated with increased odds of sustaining an injury resulting from contact with the diving board or platform (odds ratio, 16.0 and 6.9, respectively). In 2020, the incidence of diving-related injury fell to 1.6 per 100,000 population. Diving injuries are common in children and adolescents, especially in boys aged 10 to 19. There was a significant reduction in diving-related injury corresponding with the COVID-19 pandemic.


[What the cardiologist should know about physical training].
Because of the cardiovascular stresses and the potential risks of physical training, cardiologists are often asked to give an opinion on aptitude for sport. It is therefore important to understand the fundamentals of physical training. This is based on specific rules; general physical preparation, progressive nature of the activity, individualisation of training programmes, specificity of sporting activity, recovery times and planning of exercise. The two main types of training (aerobics and weight training) are used preferentially according to the type of sport but good aerobic capacity is required in all specialities. The training implies a certain physical stress and the individual has his own limitations. The cardiologist may help identify an imbalance between the two without being an expert in all sporting disciplines. In this field, the physician is no substitute for the coach but can help in managing the sportsman's health.


Association Between Arterial Stiffness and Skin Microvascular Function: The SUVIMAX2 Study and The Maastricht Study.
It has been hypothesized that arterial stiffness leads to generalized microvascular dysfunction and that individuals with type 2 diabetes mellitus (T2DM) are particularly prone to the detrimental effects of arterial stiffness. However, evidence for an association between stiffness and markers of generalized microvascular dysfunction is lacking. We therefore investigated the association between arterial stiffness and skin microvascular function in individuals without and with T2DM. Cross-sectional data were used of The Supplementation en Vitamines et Mineraux Antioxydants 2 (SUVIMAX2) Study (n = 284/62.2 years/48.6% women/0% T2DM (by design)) and The Maastricht Study (n = 737/59.7 years/45.2% women/28.8% T2DM (by design)). Arterial stiffness was determined by carotid-femoral pulse wave velocity (cfPWV). Skin capillaroscopy was used to determine capillary density at baseline, and during reactive hyperemia and venous congestion. Laser Doppler flowmetry was used to assess acetylcholine- and local heating-induced vasoreactivity, and skin flowmotion. In The SUVIMAX2 Study, cfPWV (per +1 SD) was not associated with baseline capillary density (regression coefficient: -0.48 (95% confidence interval: 2.37; 1.41)) or capillary recruitment during venous congestion (0.54% (-0.74; 1.81%)). In addition, cfPWV was not associated with acetylcholine (-0.02% (-0.14; 0.10%)) or local heating-induced vasoreactivity (0.03% (-0.07; 0.12%)). In The Maastricht Study, in individuals without T2DM, cfPWV was not associated with baseline capillary density (-1.20 (-3.17; 0.77)), and capillary recruitment during reactive hyperemia (1.22% (-0.41; 2.84%)) or venous congestion (1.50% (-0.25; 3.25%)). In addition, cfPWV was not associated with flowmotion (-0.01 (-0.07; 0.06)). Results were adjusted for age and sex. Additional adjustments for confounders did not materially change these results. Results were qualitatively similar in individuals with T2DM. Arterial stiffness is not associated with skin microvascular function, irrespective of the presence of T2DM.


[Principal component analysis and integral methods of cerebral vascular hemodynamic parameters].
To establish a predicting model for stroke according to cerebral vascular hemodynamic indexes and major risk factors of stroke. Participants selected from a stroke cohort with 25,355 population in China. The first step was to carry out principal component analysis using CVHI. Logistic regression with principal component and main risk factors of stroke were then served as independent variables and stroke come on as dependent variables. The predictive model was established according to coefficient of regression and probability of each participant was also estimated. Finally, ROC curve was protracted and predictive efficacy was measured. The accumulative contribution rates of four principal components were 58.1%, 79.4%, 88.4% and 94.6% respectively. Seven variables were being selected into the equation with the first to fourth principal component as history of hypertension, age and sex. Area under ROC curve was 0.855 and optimal cut-off point was probability over 0.05. Sensitivity, specificity and accuracy of stroke prediction were 80.7%, 78.5% and 78.5% respectively. The model established by principal component and regression could effectively predict the incidence of stroke coming on.


Tg-SwDI transgenic mice exhibit novel alterations in AbetaPP processing, Abeta degradation, and resilient amyloid angiopathy.
Alzheimer's disease (AD) is characterized by the accumulation of extracellular insoluble amyloid, primarily derived from polymerized amyloid-beta (Abeta) peptides. We characterized the chemical composition of the Abeta peptides deposited in the brain parenchyma and cerebrovascular walls of triple transgenic Tg-SwDI mice that produce a rapid and profuse Abeta accumulation. The processing of the N- and C-terminal regions of mutant AbetaPP differs substantially from humans because the brain parenchyma accumulates numerous, diffuse, nonfibrillar plaques, whereas the thalamic microvessels harbor overwhelming amounts of compact, fibrillar, thioflavine-S- and apolipoprotein E-positive amyloid deposits. The abundant accretion of vascular amyloid, despite low AbetaPP transgene expression levels, suggests that inefficient Abeta proteolysis because of conformational changes and dimerization may be key pathogenic factors in this animal model. The disruption of amyloid plaque cores by immunotherapy is accompanied by increased perivascular deposition in both humans and transgenic mice. This analogous susceptibility and response to the disruption of amyloid deposits suggests that Tg-SwDI mice provide an excellent model in which to study the functional aftermath of immunotherapeutic interventions. These mice might also reveal new avenues to promote amyloidogenic AbetaPP processing and fundamental insights into the faulty degradation and clearance of Abeta in AD, pivotal issues in understanding AD pathophysiology and the assessment of new therapeutic agents.


Effects of mesiodens on adjacent permanent teeth: a retrospective study in Korean children based on cone-beam computed tomography.
Mesiodens can be associated with several complications. The optimal age for treatment, however, remains controversial. To investigate the three-dimensional (3D) positions of mesiodens using cone-beam computed tomography (CBCT) and determine the association of eruption-related complications of mesiodens with these 3D positions and delayed development of the central incisors. In total, 293 Korean children (383 supernumerary teeth) aged 4-10 years with no history of orthodontic treatment were included. CBCT and panoramic radiography data for all patients were retrospectively investigated with regard to the 3D positions of mesiodens, apical maturity of the permanent first molars, delayed development of the central incisors relative to the apical maturity of the permanent first molars (Nolla's stage), and eruption-related complications of mesiodens. Eruption-related complications were not correlated with any 3D characteristic other than the 'within the arch' position of mesiodens, while they showed a significant correlation with delayed development of the central incisors (P < 0.05). Mesiodens caused eruption-related complications in 33.7% patients. Moreover, the risk of these complications was higher when mesiodens caused delayed development of the central incisors. These findings can aid clinicians in planning appropriate and timely treatment for mesiodens, with focus on minimising patient discomfort.


Molecular characterization of virulence determinants of Stenotrophomonas maltophilia strains isolated from patients affected by cystic fibrosis.
Stenotrophomonas maltophilia is an emerging nosocomial bacterial pathogen which is currently isolated with increasing frequency from the airways of cystic fibrosis (CF) patients. In this study 13 S. maltophilia strains (11 isolated from the airways of independent CF patients, and two non-CF respiratory reference strains) have been characterized for the expression of several virulence-associated factors. In particular, the ability to form biofilm on abiotic surfaces has been determined and correlated with different features, such as motility, adherence and the ability to invade A549 respiratory epithelial cells. Moreover, the presence of a flagellum-associated gene as well as that of the StmPr1 gene, which encodes an extracellular protease, have been determined by Southern blot hybridization. Our data indicate that the different degree of biofilm formation exhibited by the 11 CF isolates does not correlate with motility, ability to adhere to and invade A549 cells, or with the presence of flagella. On the other hand, among the CF isolates the StmPr1 gene was found only in two strains, both able to establish chronic lung infections in CF patients. Moreover, only four of the strains analyzed show a temperature-independent antibiotic-resistance profile, suggesting either a different origin of these strains or an intervening adaptation to host tissues.


An increased standardised mortality ratio for liver cancer among polyvinyl chloride workers in Taiwan.
To determine the standardised mortality ratio (SMR) corresponding to different causes of death in workers from polyvinyl chloride polymerisation factories in Taiwan. Retrospective cohort study of workers from six polyvinyl chloride polymerisation factories in Taiwan. A total of 3293 male workers who had been employed for at least one year during the period 1 January 1950 to 31 December 1992, and were alive on 1 January 1985 were included for analysis. Using data acquired from Taiwan's National Mortality Registry, it was found that 144 of these workers died during the period 1985-97. The follow up rate was 99% with a total number of person-years at risk of 40 557. SMR for all causes of death was 0.78, indicating a possible "healthy worker" effect. The SMR for liver cancer decreased with increasing age of first exposure to vinyl chloride monomer. This association was more prominent for workers who were first employed in the industry prior to 1970 (SMR 4.82). Medical records indicated that most liver cancers in this study were hepatocellular carcinoma. Polyvinyl chloride workers may experience a higher risk of developing liver cancer, particularly hepatocelluar carcinoma.


Features of Postnatal Hippocampal Development in a Rat Model of Sporadic Alzheimer's Disease.
Aging is the major risk factor of the most common (∼95% of cases) sporadic Alzheimer's disease (AD). Accumulating data indicate middle age as a critical period for the relevant pathological processes, however, the question of when AD starts to develop remains open. It has been reported only recently that in the early postnatal period-when brain development is completing-preconditions for a decrease in cognitive abilities and for accelerated aging can form. Here, we hypothesized that specific features of early postnatal brain development may be considered some of the prerequisites of AD development at an advanced age. To test this hypothesis, we used OXYS rats, which are a suitable model of sporadic AD. The duration of gestation, litter size, and weight at birth were lower in OXYS rats compared to control Wistar rats. The shortened duration of gestation may result in developmental retardation. Indeed, we noted decreased locomotor activity and increased anxiety in OXYS rats already at a young age: possible signs of altered brain development. We demonstrated retardation of the peak of postnatal neurogenesis in the hippocampal dentate gyrus of OXYS rats. Delayed neuronal maturation led to alterations of mossy-fiber formation: a shortened suprapyramidal bundle and longer infrapyramidal bundle, less pronounced fasciculation of granule cells' axons, and smaller size and irregular shape of nuclei in the CA3 pyramidal layer. These changes were accompanied by altered astrocytic migration. The observed features of early development may be considered some of the risk factors of the AD-like pathology that manifests itself in OXYS rats late in life.


Three-dimensional reconstruction based on images from spiral high-resolution computed tomography of the temporal bone: anatomy and clinical application.
The aim of this study was to investigate the usefulness of a three-dimensional (3D) reconstruction of computed tomography (CT) images in determining the anatomy and topographic relationship between various important structures. Using 40 ears from 20 patients with various otological diseases, a 3D reconstruction based on the image data from spiral high-resolution CT was performed by segmentation, volume-rendering and surface-rendering algorithms on a personal computer. The 3D display of the middle and inner ear structures was demonstrated in detail. Computer-assisted measurements, many of which could not be easily measured in vivo, of the reconstructed structures provided accurate anatomic details that improved the surgeon's understanding of spatial relationships. A 3D reconstruction of temporal bone CT might be useful for education and increasing understanding of the anatomical structures of the temporal bone. However, it will be necessary to confirm the correlation between the 3D reconstructed images and histological sections through a validation study.


Thermal safety of ultrasound-enhanced ocular drug delivery: A modeling study.
Delivery of sufficient amounts of therapeutic drugs into the eye for treatment of various ocular diseases is often a challenging task. Ultrasound was shown to be effective in enhancing ocular drug delivery in the authors' previous in vitro and in vivo studies. The study reported here was designed to investigate the safety of ultrasound application and its potential thermal effects in the eye using PZFlex modeling software. The safety limit in this study was set as a temperature increase of no more than 1.5 °C based on regulatory recommendations and previous experimental safety studies. Acoustic and thermal specifications of different human eye tissues were obtained from the published literature. The tissues of particular interest in this modeling safety study were cornea, lens, and the location of optic nerve in the posterior eye. Ultrasound application was modeled at frequencies of 400 kHz-1 MHz, intensities of 0.3-1 W/cm(2), and exposure duration of 5 min, which were the parameters used in the authors' previous drug delivery experiments. The baseline eye temperature was 37 °C. The authors' results showed that the maximal tissue temperatures after 5 min of ultrasound application were 38, 39, 39.5, and 40 °C in the cornea, 39.5, 40, 42, and 43 °C in the center of the lens, and 37.5, 38.5, and 39 °C in the back of the eye (at the optic nerve location) at frequencies of 400, 600, 800 kHz, and 1 MHz, respectively. The ocular temperatures reached at higher frequencies were considered unsafe based on current recommendations. At a frequency of 400 kHz and intensity of 0.8 W/cm(2) (parameters shown in the authors' previous in vivo studies to be optimal for ocular drug delivery), the temperature increase was small enough to be considered safe inside different ocular tissues. However, the impact of orbital bone and tissue perfusion should be included in future modeling efforts to determine the safety of this method in the whole orbit especially regarding potential adverse optic nerve heating at the location of the bone.


Implications of mass automated instruments on medical practice.
The clinical laboratory is in a stage of change which has been the direct result of an influx of technology and the current demand for lower costs and increased productivity. There is no significant trend anticipated in the future which would forestall this particular process. The practicing physician can anticipate a fairly marked reduction in the cost of individual tests and, likewise, a marked increase in the amount of available information. There will be a larger clerical function involved in the review of such information along with a series of relevant problems related to the actual size of the new data base. One of the most significant problems related to this increase in numerical reporting will be the statistical problem of the "abnormal-normal." Statistical misclassification must be considered with each abnormal test and a specific approach must be taken to these tests to minimize the inconvenience to the patient. It is recommended that any unsuspected abnormal test(s) that is discovered be repeated as a single test(s) through a reference method. Reordering of the test battery or screen will only offer another possibility for statistical misinterpretation. If the test on isolated evaluation does appear abnormal, then this should call for the routine evaluation of this particular condition. Multivariate statistical analysis could eliminate this probability dilemma, yet is presently experimental and is not in routine use within any clinical setting. We can look forward to the evolution of such a process through the mechanism of a hospital and laboratory communication system which will allow the physician to work with an evaluation process capable of handling these large volumes of numbers (22). Such programs are on the horizon and should be anticipated within the next five years in some of the larger centers that have this new instrumentation.


Active pulse shaping for end-pumped Nd:YVO4 amplifier with high gain.
We demonstrated the active shaping for a solid-state Nd:YVO4 amplifier with a high average gain of 39.2 dB. The average output power was 8.3 W with respect to the input power of 1 mW. A range of common and useful pulse shapes was generated at the final output. In addition, a very flat square pulse was produced with a root-mean-square less than 3% in amplitude. A numerical method was proposed to realize active shaping without an experimental test for the Nd:YVO4 amplifier, showing great potential for the design of lasers with both high peak power (>100 kW) and a desired pulse shape.


Aspirin use and counseling about aspirin among patients with diabetes.
Despite being a safe, effective therapy for lowering cardiovascular risk, only 20% of diabetic patients were using aspirin in the early 1990s. This study examines current physician practices and the use of aspirin therapy by individuals with diabetes. A random sample of diabetic patients receiving care in the Department of Veterans Affairs health care system were surveyed during January-March 2000. The association between aspirin counseling, aspirin use, and reported coronary vascular disease (CVD) and classical CVD risk factors were examined using logistic regression. The effect of increasing aspirin use on risk of myocardial infarction (MI) and cardiovascular mortality was demonstrated by simulation. Seventy-one percent of respondents reported being counseled about aspirin use, and 66% were taking daily aspirin. Individuals with known CVD were more likely to be counseled (odds ratio [OR] 4.9, 95% CI 2.9-8.1) and to use aspirin (2.1, 1.2-3.7). The factor most strongly associated with aspirin use was having been counseled about aspirin therapy by a doctor. We estimate that for this population, increasing daily aspirin use to 90% could prevent an additional 11,000 MIs and potentially save >8,000 lives. Compared with previous reports, a substantial proportion of these diabetic patients have been counseled about and use aspirin. Most clinicians recognize aspirin as an important treatment for patients with preexisting coronary disease. However, since diabetes is now considered a CVD equivalent, it is imperative that clinicians include counseling about aspirin therapy as a care priority for all their diabetic patients, as this simple intervention may prevent many cardiovascular events and deaths.


CD4+ and CD8+ T cells are both needed to induce paraneoplastic neurological disease in a mouse model.
Paraneoplastic neurological disorders (PNDs) are rare human autoimmune diseases that mostly affect the central nervous system (CNS). They are triggered by an efficient immune response against a neural self-antigen that is ectopically expressed in neoplastic tumors. Due to this shared antigenic expression, the immune system reacts not only to tumor cells but also to neural cells resulting in neurological damage. Growing data point to a major role of cell-mediated immunity in PNDs associated to autoantibodies against intracellular proteins. However, its precise contribution in the pathogenesis remains unclear. In this context, our study aimed at investigating the impact of anti-tumor cellular immune responses in the development of PND. To this end, we developed an animal model mimicking PND. We used a tumor cell line expressing the hemagglutinin (HA) of influenza virus to induce an anti-tumor response in CamK-HA mice, which express HA in CNS neurons. To promote and track the T cell response against the HA antigen, naïve HA-specific CD8+ and/or CD4+ T cells, originating from TCR-transgenic animals, were transferred into these mice. We demonstrate that HA-expressing tumors, but not control tumors, induce in vivo activation, proliferation and differentiation of naïve HA-specific CD4+ and CD8+ T cells into effector cells. Moreover, both T cell subsets were needed to control tumor growth and induce CNS inflammation in CamK-HA mice. Thus, this new mouse model provides further insight into the cellular mechanisms whereby a potent anti-tumor immunity triggers a cancer-associated autoimmune disease, and may therefore help to develop new therapeutic strategies against PND.


Activation of murine polymorphonuclear neutrophils for fungicidal activity with supernatants from antigen-stimulated immune spleen cell cultures.
An in vitro model of in vivo immunological activation of murine polymorphonuclear neutrophils (PMN) was developed. Culture supernatants of spleen cells from Blastomyces dermatitidis-immunized mice stimulated with B. dermatitidis antigens in vitro were studied. Incubation of the supernatants with thioglycolate-elicited PMN enabled the cells to significantly reduce (31 +/- 6%) B. dermatitidis inoculum CFU. Optimum production of active supernatants occurred after 4 to 6 days of stimulation in vitro and required 200 micrograms of nonviable B. dermatitidis cells per ml. Generation of activity by immune spleen cells was shown to be antigen specific in that stimulation with a heterologous antigen or stimulation of nonimmune spleen cells with B. dermatitidis antigen did not produce active supernatants. The activity in supernatants was dose dependent, nondialyzable (molecular weight greater than or equal to 14,000), and relatively heat labile (80 degrees C, 30 min). Activation of PMN by supernatants for fungicidal activity against B. dermatitidis required only a short incubation period (1 h) followed by a 2-h coculture (challenge) period. Stimulation of normal spleen cells with concanavalin A also resulted in the production of supernatants capable of activating PMN for significant fungicidal activity (31.1 +/- 8.5%). These findings demonstrate for the first time a link between soluble factors produced by antigen stimulation of sensitized lymphoid cells and activation of PMN for enhanced microbicidal activity. Such a process defines an additional immune defense mechanism whereby the immune host may clear specific microorganisms.


Sequential changes in Rotterdam CT scores related to outcomes for patients with traumatic brain injury who undergo decompressive craniectomy.
OBJECT Rotterdam CT scoring is a CT classification system for grouping patients with traumatic brain injury (TBI) based on multiple CT characteristics. This retrospective study aimed to determine the relationship between initial or preoperative Rotterdam CT scores and TBI prognosis after decompressive craniectomy (DC). METHODS The authors retrospectively reviewed the medical records of all consecutive patients who underwent DC for nonpenetrating TBI in 2 hospitals from January 2006 through December 2013. Univariate and multivariate logistic regression and receiver operating characteristic (ROC) curve analyses were used to determine the relationship between initial or preoperative Rotterdam CT scores and mortality at 30 days or Glasgow Outcome Scale (GOS) scores at least 3 months after the time of injury. Unfavorable outcomes were GOS Scores 1-3 and favorable outcomes were GOS Scores 4 and 5. RESULTS A total of 48 cases involving patients who underwent DC for TBI were included in this study. Univariate analyses showed that initial Rotterdam CT scores were significantly associated with mortality and both initial and preoperative Rotterdam CT scores were significantly associated with unfavorable outcomes. Multivariable logistic regression analysis adjusted for established predictors of TBI outcomes showed that initial Rotterdam CT scores were significantly associated with mortality (OR 4.98, 95% CI 1.40-17.78, p = 0.01) and unfavorable outcomes (OR 3.66, 95% CI 1.29-10.39, p = 0.02) and preoperative Rotterdam CT scores were significantly associated with unfavorable outcomes (OR 15.29, 95% CI 2.50-93.53, p = 0.003). ROC curve analyses showed cutoff values for the initial Rotterdam CT score of 5.5 (area under the curve [AUC] 0.74, 95% CI 0.59-0.90, p = 0.009, sensitivity 50.0%, and specificity 88.2%) for mortality and 4.5 (AUC 0.71, 95% CI 0.56-0.86, p = 0.02, sensitivity 62.5%, and specificity 75.0%) for an unfavorable outcome and a cutoff value for the preoperative Rotterdam CT score of 4.5 (AUC 0.81, 95% CI 0.69-0.94, p < 0.001, sensitivity 90.6%, and specificity 56.2%) for an unfavorable outcome. CONCLUSIONS Assessment of changes in Rotterdam CT scores over time may serve as a prognostic indicator in TBI and can help determine which patients require DC.


Main-chain flexibility and hydrophobicity of ionenes strongly impact their antimicrobial activity: an extended study on drug resistance strains and Mycobacterium.
The spread of antibiotic-resistant pathogens and the resurgence of tuberculosis disease are major motivations to search for novel antimicrobial agents. Some promising candidates in this respect are cationic polymers, also known as synthetic mimics of antimicrobial peptides (SMAMPs), which act through the membrane-lytic mechanism. Development of resistance toward SMAMPs is less likely than toward currently employed antibiotics; however, further studies are needed to better understand their structure-activity relationship. The main objective of this work is to understand the cross-influence of hydrophobicity, main-chain flexibility, and the topology of ionenes (polycations containing a cationic moiety within the main-chain) on activity. To fulfill this goal, a library of ionenes was developed and compared with previously investigated molecules. The obtained compounds display promising activity against the model microorganisms and drug-resistance clinical isolates, including Mycobacterium tuberculosis. The killing efficiency was also investigated, and results confirm a strong effect of hydrophobicity, revealing higher activity for molecules possessing the flexible linker within the polymer main-chain.


Health extension service utilization and associated factors in East Gojjam zone, Northwest Ethiopia: A community-based cross-sectional study.
Health Extension Program is a preventive, promotive, and basic curative service targeting households to improve the health status of families with the effective implementation of 16 health extension packages. We, therefore, did this study to assess health extension package utilization and associated factors in the East Gojjam zone, Northwest Ethiopia. A community-based mixed cross-sectional study was conducted on households of East Gojjam Zone, from January 1 to April 30, 2020. A multistage sampling procedure was used to select 806 study participants in this study. We used EPI info version 7 for data entry and SPSS version 24 software for cleaning and analysis. Variables having a P-value of less than 0.25 in the bivariate logistic regression analysis were fitted into the multivariable logistic regression model. The 95% confidence interval of odds ratio was computed and a variable having P-value less than 0.05 in the multivariable logistic regression analysis was considered as statistically significant. The study showed that 119 (14.8%) respondents have utilized health extension packages. Knowledge health extension package (AOR = 1.84, 95% CI: 1.22, 2.79), residence (AOR = 3.55, 95% CI: 1.99,6.33),visited health post(AOR = 1.63, 95% CI: 1.054,2.50), home visited by health extension worker (AOR = 1,68, 95% CI: 1.025,2.74) and involving in model family training(AOR = 2.10, 95% CI: 1.38,3.215) were significant factors for health extension service utilization. The magnitude of health extension service utilization was low since the Ethiopian government recommends 100% health extension service utilization coverage. Knowledge of health extension package, residence, health post-visit, home visit, and model family training were significant factors for health extension service utilization. So expanding the model family training and strict home-to-home visit especially in rural areas may increase the health extension package utilization.


Non-Judicial Hanging in Guilan Province, Iran between 2011 and 2013.
Hanging is one of the most commonly used way to commit suicide in many countries. This method used in suicide is considered a problem in Iran too, but no clear data exists regarding hanging in different regions or the country as a whole. Because of the epidemiologic differences in non-judicial hanging in different regions, this study aimed to assess it in Gilan province, Iran between 2011 and 2013. In this cross-sectional study, profiles of hanging cases registered in Poorsina hospital in Gilan, Iran between 2011 and 2013 were evaluated. Age, sex, marital status, place of residency, level of education, occupation, history of suicide, history of clinical illness, season of suicide and hanging outcome were evaluated. 59 cases of hanging (mean age 31.4 ± 13.1 years and 83.0% male) were evaluated. 12 (20.34%) suffered from psychological disorders, and 9 (15.2%) confessed to substance abuse. 7 (11.9%) had a history of suicide attempts by hanging. Hanging was significantly higher in men (p<0.001), people with an education level of less than high school diploma (p=0.02) and the unemployed (p<0.05) patients. In the end, 20 (33.9%) of these attempts resulted in death. The results of this study showed that in 2 years, 59 cases committed suicide by hanging themselves, 33.9% of which finally died. Committing suicide by hanging was significantly more prevalent in men, people with an education level of less than high school diploma and the unemployed.


Cannabinoid receptor 1 controls human mucosal-type mast cell degranulation and maturation in situ.
Because many chronic inflammatory and allergic disorders are intimately linked to excessive mast cell (MC) numbers and activation, it is clinically important to understand the physiologic mechanisms preventing excess MC accumulation/degranulation in normal human tissues. Because endocannabinoids are increasingly recognized as neuroendocrine regulators of MC biology, we investigated how cannabinoid receptor (CB) 1 signaling affects human mucosal-type mast cells (hMMCs). Using organ-cultured nasal polyps as a surrogate tissue for human bronchial mucosa, we investigated how CB1 stimulation, inhibition, or knockdown affects hMMC biology using quantitative (immuno)histomorphometry and electron microscopy. Kit(+) hMMCs express functional CB1 in situ. Blockade of CB1 signaling (with the specific CB1 antagonist N-(piperidin-1-yl)-1-(2,4-dichlorophenyl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide [AM251] or CB1 gene knockdown) enhanced hMMC degranulation and increased total numbers without affecting their proliferation in situ. This suggests that inhibiting CB1 signaling induces hMMC maturation from resident progenitor cells within human mucosal stroma. hMMC maturation was induced at least in part through upregulating stem cell factor production. Both the prototypic endocannabinoid anandamide and the CB1-selective agonist arachidonyl-2-chloroethylamide effectively counteracted secretagogue-triggered excessive hMMC degranulation. The current serum-free nasal polyp organ culture model allows physiologically and clinically relevant insights into the biology and pharmacologic responses of primary hMMCs in situ. In human airway mucosa hMMC activation and maturation are subject to a potent inhibitory endocannabinoid tone through CB1 stimulation. This invites one to target the endocannabinoid system in human airway mucosa as a novel strategy in the future management of allergic diseases.


New cell-cell adhesion inhibitors from Streptomyces sp. UMA-044.
Three compounds, NP25301 (1), NP25302 (2) and bohemamine (3), inhibitors of cell adhesion based on LFA-1/ICAM-1, were isolated from the cultured broth of the strain Streptomyces sp. UMA-044. New compounds 1 and 2 were identified as 2-(3'-carbamoylphenoxy)acrylic acid methyl ester and deoxybohemamine, respectively, based on spectroscopic analyses. Compounds 1 approximately 3 inhibited adhesion of HL-60 cells to CHO-ICAM-1 cells at IC50 values of 29.5 microg/ml for 1, 24.3 microg/ml for 2, and 27.2 microg/ml for 3.


[A study of portal blood flow changes in patients with early dumping syndrome and patients with oxyhyperglycemia].
Changes of portal blood flow in patients with early dumping syndrome and those with oxyhyperglycemia were determined after oral ingestion of 300ml of 25% glucose solution by a linear-type B mode electroscanner and pulsed Doppler flowmeter. In normal volunteers, the portal blood flow increased slowly to the peak level of 201% of fasting value at 40 minutes. The portal blood flow in postgastrectomy patients reached the peak value more quickly, with the peak level of 245% at 10 minutes in patients with the early dumping syndrome, and of 172% at 15 minutes in patients without the syndrome. The portal blood flow in patients with early dumping syndrome was significantly greater than that without the syndrome. Patients with early dumping syndrome had characteristic symptoms such as general malaise, cold sweat, nausea, abdominal pain, diarrhea in accordance with increased portal blood flow. Patients with high grade oxyhyperglycemia (peak blood sugar after 75g OGTT greater than 250mg/dl) had significantly higher portal blood flow and peripheral blood sugar than those with low grade oxyhyperglycemia (peak blood sugar less than 250mg/dl) without difference in IRI between the two groups.


[The effects of H2 blockers on gastric flora and sputum culture].
Gastric juice and sputum of 12 patients, who had entered the intensive care unit postoperatively and received respiratory management, were examined for bacteria and their relationship with gastric pH was investigated. Gastric bacteria were detected in only 3 specimens out of 14 (21.4%) when the pH was under 3.5, and when the pH was above 3.5, gastric bacteria were detected in 33 specimens out of 35 (94.3%). Proliferation of gastric flora was observed as the pH increased. In 7 cases, Gram-negative bacilli (important etiologically as a cause of pneumonia) were detected. Gram-negative bacilli were also detected in sputum culture and these were found to be of the same bacteria type as those found in the gastric juice. However, no evident cases of pneumonia were observed, and proliferation of gastric bacteria did not increase the incidence of postoperative pneumonia.


The background assimilation effect: Facial emotional perception is affected by surrounding stimuli.
The perception of facial emotion is not only determined by the physical features of the face itself but also be influenced by the emotional information of the background or surrounding information. However, the details of such effect are not fully understood. Here, the authors tested the perceived emotion of a target face surrounded by stimuli with different levels of emotional valence. In Experiment 1, four types of objects were divided into three groups (negative, unpleasant flowers and unpleasant animals; mildly negative (neutral), houses; positive, pleasant flowers). In Experiment 2, three groups of surrounding faces with different social-emotional valence (negative, neutral, and positive) were formed with the memory of affective personal knowledge. The data from two experiments showed that the perception of facial emotion can be influenced and modulated by the emotional valence of the surrounding stimuli, which can be explained by assimilation: the positive stimuli increased the valence of a target face, while the negative stimuli comparatively decreased it. Furthermore, the neutral stimuli also increased the valence of the target, which could be explained by the social positive effect. Therefore, the process of assimilation is likely to be a high-level emotional cognition rather than a low-level visual perception. The results of this study may help us better understand face perception in realistic scenarios.


Energy metabolism during late gestation and lactation in multiparous sows in relation to backfat thickness and the interval from weaning to first oestrus.
Ten crossbred, fourth or fifth parity sows were divided into 2 groups - high (H) and low (L)- according to their backfat thickness 9 days before parturition. Body weight, backfat thickness and litter weight were recorded repeatedly during a 5 week lactation period. The length of the interval from weaning to first oestrus was also noted. All sows were fed a commercial diet (11.9 MJ/kg, 14.5% crude protein). During gestation, daily food intake was 2.2 kg/sow, while during lactation it was 3.0 kg/sow plus 0.4 kg/piglet. Blood samples were drawn on day 9 before parturition and on days 2, 7, 14 and 21 of lactation. The samples were analysed to determine concentrations of glucose, urea nitrogen, creatinine, triglycerides, free fatty acids and beta-hydroxybutyric acid. In both groups, concentrations of free fatty acids and urea nitrogen were low on day 9 before parturition while those of triglycerides were high, indicating anabolism regardless of backfat thickness. During the first week of lactation, concentrations of free fatty acids increased in the H-group but not in the L-group, and concentrations of urea nitrogen were higher in the H-group. These differences, together with the greater loss of weight observed in the H-group, indicate that catabolism of maternal fat and protein depots was more pronounced in the H-group than in the L-group during this time. On day 14 of lactation, both groups showed equally low concentrations of free fatty acids, decreasing creatinine concentrations and stable triglyceride and urea nitrogen concentrations. Furthermore, weight loss during the second and third weeks of lactation was low in both groups. These facts, taken together, indicate that the catabolic rate was decreasing in both groups during this period. No differences in return to oestrus interval were noted between the groups. The present study indicates that under a restricted feeding regime the catabolic rate during the first week of lactation is higher in sows with higher backfat thickness in late gestation. As lactation progresses, a more balanced metabolism is achieved regardless of backfat thickness, which may tend to reduce differences in return to oestrous interval.


Impact of leflunomide versus biologic agents on the costs of care for rheumatoid arthritis in a managed care population.
To compare the impact of leflunomide on resource utilization and costs relative to that of etanercept and infliximab among patients with rheumatoid arthritis (RA) in a managed care setting. Data were obtained from the PharMetrics Integrated Outcomes Database for all patients newly starting 1 of the 3 medications of interest in 1999 or 2000. Claims were compiled for 180 days prior to the first prescription for study therapy and for a minimum of 90 days thereafter. Measures of interest during follow-up included the incidence of significant interventions (eg, joint injection, synovectomy), 1-year utilization of study therapy, other RA-related medications, inpatient and outpatient services, and total costs of RA-related care. Data were adjusted for variable follow-up using survival techniques. Multivariate analyses were conducted on total costs, controlling for between-group differences in demographic, clinical, and pretreatment characteristics. A total of 4069 patients were included in the study cohort (n = 2217, 1547, and 305 for leflunomide, etanercept, and infliximab, respectively). Three quarters of the cohort were female; etanercept patients were somewhat younger than leflunomide or infliximab recipients. Severity of illness (as measured by the Charlson index) was highest among infliximab patients. The incidence of significant interventions was high in all patients, but did not differ by treatment group. Use of nonsteroidal anti-inflammatory drugs (8.1 versus 8.9 claims) and narcotic analgesics (7.8 versus 8.5) was substantially lower for leflunomide than for etanercept. Costs of RA-related care were 42% to 53% lower among leflunomide patients for biologic medications ($9618 versus $16,534 and $20,263 for etanercept and infliximab, respectively), primarily as a result of lower medication costs. Findings persisted in multivariate analyses of cost. Leflunomide is associated with reduced costs of medications and other healthcare services relative to biologic medications among managed care patients with RA.


Novel anticoagulants for stroke prevention in atrial fibrillation: current clinical evidence and future developments.
Atrial fibrillation (AF) is the most common cardiac rhythm disorder and a major risk factor for ischemic stroke. Antithrombotic therapy using aspirin or vitamin K antagonists (VKA) is currently prescribed for prevention for ischemic stroke in patients with AF. A narrow therapeutic range and the need of regular monitoring of its anticoagulatory effect impair effectiveness and safety of VKA, causing a need for alternative anticoagulant drugs. Recently developed anticoagulants include direct thrombin antagonists such as dabigatran or factor Xa inhibitors such as rivaroxaban, apixaban, betrixaban, and edoxaban. Currently, data from a phase III clinical trial are available for dabigatran only, which show the direct thrombin antagonist to be at least noninferior in efficacy to VKA for the prevention of stroke and systemic embolism in patients with AF. This review focuses on current advances in the development of directly acting oral anticoagulant drugs and their potential to replace the VKA class of drugs in patients with AF.


Morphological aspects and histological effects of the attachment organ of Parabrachiella sp. (Copepoda: Lernaeopodidae) on the grey mullet, Mugil liza Valenciennes.
The genus Parabrachiella Wilson, 1915 (Lernaeopodidae) is represented by copepods that are highly adapted to a parasitic way of life. In Argentina, only P. insidiosa var. lageniformis Heller, 1865, P. chevreuxii Van Beneden, 1891 and P. spinicephala Ringuelet, 1945 have been cited, but none of these have been reported on mugilids. Recently, other species of this genus were found attached to the nasal cavities of juvenile grey mullets, Mugil liza Valenciennes, from Samborombón bay, Buenos Aires province. In this study, the prevalence and mean intensity of the Parabrachiella sp. on grey mullet is investigated. In addition, the damage the parasite imposes on its hosts is examined through evaluation of histological sections and immunostaining for proliferative cell nuclear antigen (PCNA). The morphology of the parasite's bulla is described from light and scanning electron micrographs.


Improvement of the comfort perception scale in oral mucositis.
The study was conducted to develop a valid and reliable measurement tool for determining the comfort perceptions of patients with oral mucositis. The study was carried out methodologically between April 2017 and October 2019 in outpatient chemotherapy centers and clinics in which malignant patients were treated in a university hospital and educational-research hospital in Erzurum, Turkey of the study sample comprised 380 patients who developed oral mucositis after treatment. A 'Patient Identification Information Form,' draft 'Comfort Perception Scale in Oral Mucositis' and 'General Comfort Scale' were used to collect the study data. Validity and reliability analyses were used when evaluating the data. Percentage, mean, independent groups t-test, Mann-Whitney U test, Kruskal-Wallis test, variance analysis and advanced analyzes were also used. In this study, while the face validity of the scale was obtained, the content validity index was found to be 0.62 Kaiser-Meyer-Olkin value of the scale for explanatory factor analysis was 0.94, and Bartlett's test x2 = 9142.156 (P < 0.05). For the confirmatory factor analysis, the corrected chi-square value was 3.54, the root-mean-square error was 0.082, and the scale structure was confirmed according to these results. As a result, the scale consisted of 31 items and 2 sub-scales. Item-total correlation values ranged from 0.83 to 0.33. As a result of similar scale validity, a significant negative correlation was found between the Comfort Perception Scale in Oral Mucositis and General Comfort Scale scores (P < 0.05). The Comfort Perception Scale in Oral Mucositis is a reliable and valid scale. In this study, it was determined that patient comfort was affected according to some variables.


[Toxicity study for acrylamide].
Acrylamide is one of the most important chemical materials, which has been widely used in industry. It is one kind of many contaminants in occupational environments. However, it has been reported that starchy foods cooked at high temperature contain a certain amount of acrylamide. The main acrylamide exposure route for non-professional population is intaking of high-temperature starchy foods. In this review, the studies for tumorogenesity, neurotoxicity, reproductive and developmental toxicity possibly caused by acrylamide were reported.


Taking a low glycemic index multi-nutrient supplement as breakfast improves glycemic control in patients with type 2 diabetes mellitus: a randomized controlled trial.
Dietary therapy is the mainstay of treatment for diabetes. This study examined the effect of a low glycemic index (GI) multi-nutrient supplement, consumed in place of breakfast, on glycemic control in patients with type 2 diabetes mellitus (T2DM). A total of 71 participants were randomized at a 2:1 ratio into either a breakfast replacement group or a normal breakfast group for a 12-week interventional study. The primary outcome measure was change in hemoglobin A1c (HbA1c). Nutrition status and somatometry were studied as secondary outcomes. The breakfast replacement group displayed a -0.2% absolute reduction in HbA1c (95% CI (confidence interval), -0.38% to -0.07%, p = 0.004), while the HbA1c of the control group increased 0.3% (95% CI, 0.1% to 0.5%, p = 0.005). The baseline Mini Nutritional Assessment score for both groups was 26.0 and no significant changes occurred following intervention. However, there was a statistically significant difference in body mass index between the treatment and control groups (p = 0.032) due to the weight gain in the control group (increased 0.5 kg, 95% CI was 0.2 to 0.9, p = 0.007). These data suggest that breakfast replacement with a low GI multi-nutrient supplement can improve glycemic and weight control in T2DM.


The impact of thoracic duct resection on the long-term body composition of patients who underwent esophagectomy for esophageal cancer and survived without recurrence.
We have reported the possible benefits of radical esophagectomy with thoracic duct (TD) resection in elective esophageal cancer surgery. However, the effect of TD resection on the long-term nutrition status remains unclear. Patients who underwent esophagectomy at Keio University between January 2006 and December 2018 were included, and those who had no recurrence for more than three years were evaluated. Changes in each body composition (muscle mass and body fat) were comparatively assessed between those who underwent TD resection or not, before and at, one, three and five years after surgery. Computed tomography images were analyzed on postoperative year 1, 3 and 5. This study included 217 patients categorized in the TD-resected (TD-R) (156 patients) and TD-preserved (TD-P) (61 patients) groups. The loss of muscle mass was comparable between the groups. On the other hand, the loss of adipose tissues was significantly greater in the TD-R group than in the TD-P group at one and three years after surgery, while there was no statistical difference five years after surgery. Additionally, among patients with cT1N0M0 disease in whom survival advantage of TD resection has been reported previously, the loss of muscle mass did not differ between each group. The change of muscle mass between the two groups was comparable. Although body fat mass was reduced by TD resection, it eventually recovered in the long term. In patients with esophageal cancer, TD resection may be acceptable without significant impact on body composition in the long term.


[Clinical application of AMPLATZER Vascular Plug Ⅱ in transcatheter closure of congenital coronary artery fistula in children].
To evaluate the feasibility of applying AMPLATZER Vascular Plug Ⅱ (AVP Ⅱ) in transcatheter closure of congenital coronary artery fistula in children. Transcatheter closure procedure applying AVP Ⅱ was carried out in 7 patients (3 males and 4 females, age 1.2-12.0 years) with congenital coronary artery fistula between May 2014 and September 2015 in Pediatric Cardiology Department of Guangdong Cardiovascular Institute. Selective coronary artery angiography and aortic root angiography were performed after the release of the device to evaluate the immediate therapeutic effect. Echocardiography and electrocardiography were performed at 1 day, 1 month, 3 months, 6 months, 1 year post procedure and repeated once a year during the follow-up period. Transcatheter deployment of the device was successfully accomplished in all patients. The narrowest diameter of the fistula was (8.6±2.8) mm (4.0-12.5 mm), and the size of the deployed device ranged from 10.0 to 16.0 mm. Immediate selective coronary artery angiography revealed no residual shunt in 5 patients and trivial residual shunt in 2 patients. During a mean follow-up period of 2.7 (1.0-16.0) months, echocardiography showed that 3 patients remained no residual shunt, while 2 patients had trivial residual shunt, 2 patients developed small residual shunt. Cardiac murmur disappeared post procedure in all patients. Electrocardiography showed no ST-T changes. No migration or detachment of the device was found. AVP Ⅱ is a safe and effective choice in transcatheter closure of congenital coronary artery fistula in children.


Mutation of mitochondrial ATP8 gene improves hepatic energy status in a murine model of acute endotoxemic liver failure.
Mitochondria not only generate and modulate bioenergy but also serve as biosensors for oxidative stress, and eventually become effector organelles for cell viability. Therefore, the implications of mitochondrial (dys)function in the development of multiple organ failure are profound. We investigated whether a mutation in the ATPase subunit-8 gene affects the course of endotoxemic acute liver failure. C57BL/6J (ATP8 wild type) and C57BL/6J-mt(FVB/N) (ATP8 mutant) mice were challenged with d-galactosamine (GalN) and Escherichia coli lipopolysaccharide (LPS) for induction of acute liver failure, and studied 6 h thereafter. Control mice received physiological saline only. Analysis included in vivo fluorescence microscopy of hepatic microcirculation and levels of hepatocellular apoptosis, hepatic adenosine nucleotides and oxidative stress. Additionally, survival rates were assessed. Induction of endotoxemic liver failure provoked marked liver damage, which was coexistent with a drop of total adenosine nucleotide levels and increased oxidative stress. Of interest, oxidative stress was higher in the GalN/LPS challenged ATP8 mutants compared to wild types. Concomitantly, adenosine triphosphate (ATP) levels in livers of mice carrying the ATP8 mutation remained higher than those in wild type mice. As net result, ATP8 mutants showed lower transaminase release and a tendency to better survival rate upon GalN/LPS exposure compared to wild types. Our findings demonstrate that mutation in the ATPase subunit-8 partially protects mice against endotoxemic stress, most probably due to better hepatic energy status despite elevated oxidative stress. Thus, modulating mitochondrial function to preserve bioenergetic status may be an effective strategy to protect against sepsis-induced multiorgan dysfunction.


The time-course of the synthesis of adenosine triphosphate in Ehrlich ascites-tumour cells, and the effect of 2,4-dinitrophenol.
1. In Ehrlich ascites-tumour cells kept in nitrogen at 20 degrees for 20-30min., the ATP concentration falls from about 15mumoles/g. dry wt. to 2-3mumoles/g. dry wt. 2. If oxygen is admitted to such cells, the ATP concentration rises again in 1-2min. to about 15mumoles/g. dry wt. 3. If glucose is added, in nitrogen, there is a slower increase in ATP concentration to about 6mumoles/g. dry wt., followed by a fall and then by a still slower rise. 4. With glucose and oxygen, the ATP concentration rises rapidly in 1min. to about 8mumoles/g. dry wt., then falls, and finally increases slowly to reach 15mumoles/g. dry wt. in 2hr. 5. 2,4-Dinitrophenol (0.3mm) has little effect on these processes. 6. At 1.0mm, 2,4-dinitrophenol completely inhibits the ATP synthesis dependent on the endogenous respiration, while leaving that in the presence of glucose only a little impaired in rate, and considerably greater in magnitude. 7. ATP synthesis in the presence of glucose and 1.0mm-2,4-dinitrophenol is about three times as fast in oxygen as in nitrogen.


Integrated care in patients with atrial fibrillation- a predictive heterogeneous treatment effect analysis of the ALL-IN trial.
Integrated care is effective in reducing all-cause mortality in patients with atrial fibrillation (AF) in primary care, though time and resource intensive. The aim of the current study was to assess whether integrated care should be directed at all AF patients equally. The ALL-IN trial (n = 1,240 patients, median age 77 years) was a cluster-randomized trial in which primary care practices were randomized to provide integrated care or usual care to AF patients aged 65 years and older. Integrated care comprised of (i) anticoagulation monitoring, (ii) quarterly checkups and (iii) easy-access consultation with cardiologists. For the current analysis, cox proportional hazard analysis with all clinical variables from the CHA2DS2-VASc score was used to predict all-cause mortality in the ALL-IN trial. Subsequently, the hazard ratio and absolute risk reduction were plotted as a function of this predicted mortality risk to explore treatment heterogeneity. Under usual care, after a median of 2 years follow-up the absolute risk of all-cause mortality in the highest-risk quarter was 31.0%, compared to 4.6% in the lowest-risk quarter. On the relative scale, there was no evidence of treatment heterogeneity (p for interaction = 0.90). However, there was substantial treatment heterogeneity on the absolute scale: risk reduction in the lowest risk- quarter of risk 3.3% (95% CI -0.4% - 7.0) compared to 12.0% (95% CI 2.7% - 22.0) in the highest risk quarter. While the relative degree of benefit from integrated AF care is similar in all patients, patients with a high all-cause mortality risk have a greater benefit on an absolute scale and should therefore be prioritized when implementing integrated care.


Diversity and evolution of CYCLOIDEA-like TCP genes in relation to flower development in Papaveraceae.
Monosymmetry evolved several times independently during flower evolution. In snapdragon (Antirrhinum majus), a key gene for monosymmetry is CYCLOIDEA (CYC), which belongs to the class II TCP gene family encoding transcriptional activators. We address the questions of the evolutionary history of this gene family and of possible recruitment of genes homologous to CYC in floral development and symmetry in the Papaveraceae. Two to three members of the class II TCP family were found in each species analyzed, two of which were CYC-like genes, on the basis of the presence of both the TCP and R conserved domains. The duplication that gave rise to these two paralogous lineages (named PAPACYL1 and PAPACYL2) probably predates the divergence of the two main clades within the Papaveraceae. Phylogenetic relationships among angiosperm class II TCP genes indicated that (1) PAPACYL genes were closest to Arabidopsis (Arabidopsis thaliana) AtTCP18, and a duplication at the base of the core eudicot would have given rise to two supplementary CYC-like lineages; and (2) at least three class II TCP genes were present in the ancestor of monocots and eudicots. Semiquantitative reverse transcription-polymerase chain reaction and in situ hybridization approaches in three species with different floral symmetry indicated that both PAPACYL paralogs were expressed during floral development. A pattern common to all three species was observed at organ junctions in inflorescences and flowers. Expression in the outer petals was specifically observed in the two species with nonactinomorphic flowers. Hypotheses concerning the ancestral pattern of expression and function of CYC-like genes and their possible role in floral development of Papaveraceae species leading to bisymmetric buds are discussed.


Epidemiology and pathophysiology of the association between NAFLD and metabolically healthy or metabolically unhealthy obesity.
The prevalence of nonalcoholic fatty liver disease (NAFLD) is continuing to rise in many countries, paralleling the epidemic of obesity worldwide. In the last years, the concept of metabolically healthy obesity [MHO, generally defined as obesity without metabolic syndrome (MetS)] has raised considerable scientific interest. MHO is a complex phenotype with risks intermediate between metabolically healthy individuals with normal-weight (NWMH) and patients who are obese and metabolically unhealthy (MUO, i.e. obesity with MetS). In this review we aimed to examine the association and pathophysiological link of NAFLD with MHO and MUO. Compared to NWMH individuals, patients with obesity, regardless of the presence of MetS features, are at higher risk of all-cause mortality and cardiovascular events. Moreover, MHO patients have a greater risk of NAFLD development and progression compared to NWMH individuals. However, this risk is generally lower than that of MUO patients, suggesting a stronger adverse effect of coexisting MetS disorders than obesity per se on the severity of NAFLD. Nevertheless, since MHO is a dynamic state (with a significant proportion of MHO subjects progressing to MUO over time) and NAFLD itself may predict the transition from MHO to MUO, we believe that any effort should be made to identify NAFLD in all obese individuals, although they appear to be "metabolically healthy". Future research is needed to better understand the role of NAFLD and other pathogenic factors potentially involved in the transition from MHO to MUO and to elucidate how this transition may affect the presence and severity of NAFLD.


Immunoexpression of extracellular matrix proteins in human salivary gland development.
Immunoexpression of the extracellular matrix (ECM) proteins laminin, fibronectin, tenascin and types I, III and IV collagen was analyzed in the major and minor salivary glands of seven human fetuses at different gestational ages. The results showed the presence and localization of laminin, collagen IV and fibronectin around glandular structures at all stages of development. Tenascin was only detectable around excretory ducts. In the earliest stages of development, type I and type III collagen were presented as fine fibers delineating the glandular structures and delimiting the extension of the future lobule. As glandular development proceeded, the lobule was gradually filled with collagens and glandular tissue.


[Imaging of thoracic pathology in patients with AIDS].
The imaging features of infectious and non-infectious pathologies in HIV patients with AIDS (less than 200 CD4/mm3) are illustrated. Opportunistic infections, tumors and vascular pathologies have variable appearances based on the degree of immunosuppression and patient compliance with opportunistic infection prophylaxis. Because of advances in retroviral treatments and wider use of anti-infectious prophylaxis, thoracic pathologies in AIDS patients are less frequent but must nonetheless be recognized, and diagnosis should be suggested in patients with unknown serologic status.


Long-pulsed Nd: YAG Laser and Intense Pulse Light-755 nm for Idiopathic Facial Hirsutism: A Comparative Study.
Hirsutism means excessive terminal hair growth in a female in male pattern distribution. Perception of hirsutism is subjective. Permanent laser hair reduction is a slow process taking many sessions and tracking of improvement parameters is tedious. Hence, a lot of confusion still exists regarding the type of laser most beneficial for treatment. The aim of this study was to compare the effectiveness and safety profile of long-pulsed Nd: YAG laser (1064 nm) and intense pulse light (IPL)-755 nm in management of idiopathic facial hirsutism. Open-labelled, randomly allocated experimental study. The study included 33 cases of idiopathic facial hirsutism. Patients were randomly divided into Group A, treated with long-pulsed Nd: YAG laser and Group B, treated with IPL-755 for a total of six sessions at 1 month interval. Chi-square test was used in Medcalc® version 9.0 and the test of significance was taken to be P < 0.05. Average percentage of improvement in Group A, according to patients at each sessions were 46.33%, 70.66%, 81.66%, 84.67%, 85.33%, 87.33% and that in Group B were 28.06%, 39.72%, 52.22%, 64.72%, 67.78%, 71.11%, respectively. Excellent response (>75% reduction in hair) after six sessions in Group A was seen in fourteen (93.33%) out of fifteen patients, whereas in Group B, it was seen only in three (16.66%) out of eighteen patients. In Group A, erythema was seen in 26.67%, perifollicular edema and hyperpigmentation in 13.33% each. In Group B, erythema was seen in 50% patients, perifollicular edema in 16.67% and hyperpigmentation in 38.89% patients. Long-pulsed Nd: YAG Laser (1064 nm) is better than IPL-755 nm in terms of safety and effectiveness in the management of idiopathic facial hirsutism.


Making sense of abbreviations in nursing notes: A case study on mortality prediction.
Unstructured data from electronic health records hold potential for improving predictive models for health outcomes. Efforts to extract structured information from the unstructured data used text mining methodologies, such as topic modeling and sentiment analysis. However, such methods do not account for abbreviations. Nursing notes have valuable information about nurses' assessments and interventions, and the abbreviation use is common. Thus, abbreviation disambiguation may add more insight when using unstructured text for predictive modeling. We present a new process to extract structured information from nursing notes through abbreviation normalization, lemmatization, and stop word removal. Our study found that abbreviation disambiguation in nursing notes for subsequent topic modeling and sentiment analysis improved prediction of in-hospital and 30-day mortality while controlling for comorbidity.


Synaptic Ensemble Underlying the Selection and Consolidation of Neuronal Circuits during Learning.
Memories are crucial to the cognitive essence of who we are as human beings. Accumulating evidence has suggested that memories are stored as a subset of neurons that probably fire together in the same ensemble. Such formation of cell ensembles must meet contradictory requirements of being plastic and responsive during learning, but also stable in order to maintain the memory. Although synaptic potentiation is presumed to be the cellular substrate for this process, the link between the two remains correlational. With the application of the latest optogenetic tools, it has been possible to collect direct evidence of the contributions of synaptic potentiation in the formation and consolidation of cell ensemble in a learning task specific manner. In this review, we summarize the current view of the causative role of synaptic plasticity as the cellular mechanism underlying the encoding of memory and recalling of learned memories. In particular, we will be focusing on the latest optoprobe developed for the visualization of such "synaptic ensembles." We further discuss how a new synaptic ensemble could contribute to the formation of cell ensembles during learning and memory. With the development and application of novel research tools in the future, studies on synaptic ensembles will pioneer new discoveries, eventually leading to a comprehensive understanding of how the brain works.


Clinical significance of incision location on guided bone regeneration: human study.
Membrane exposure has been associated with poor clinical outcomes in guided bone regeneration. This prospective human study examined the effect of incision locations on flap survival and membrane exposure. Twenty-nine implant-associated buccal dehiscence defects in 25 patients were augmented using particulate mineralized human allograft. Ten sites received a collagen bioabsorbable membrane, 10 sites received acellular dermal matrix, and nine sites were treated with bone graft alone. All implants achieved primary stability and passive flap tension at the time of flap closure. Incision location was measured as the distance from the initial incision line to the mucogingival junction. The same measurements were made at 2 weeks and 1 month to represent the length of the flap that survived. The length of the flap that survived at 2 weeks was compared to the mean width of buccal keratinized gingiva (KG) of adjacent teeth. Other clinical parameters recorded included incidence of early membrane exposure and gingival thickness at mid-crest and 6 mm buccal and lingual to the mid-crest at baseline. At 2 weeks, 10 sites experienced early exposure. Exposed sites that were not covered by 1 month remained exposed. Membrane-treated groups showed no significant difference between the width of adjacent buccal KG and the length of the flap that survived at 2 weeks. The length of the flap that survived beyond the mean width of adjacent KG was significantly greater for the graft alone group (1.6 +/- 0.4 mm; P = 0.002). When the gingival thicknesses of exposed and non-exposed cases were compared, only palatal/lingual gingival thickness showed a significant difference (P = 0.002). Within the limits of the study, it was concluded that the location of the crestal incision might be a significant factor in reducing the incidence of membrane exposure by minimizing flap necrosis. The mean KG width of adjacent teeth may be used as a guide to determine the initial incision location. However, this effect may be less significant in palatal/lingual gingiva >3.0 mm.


Strategic planning for skills and simulation labs in colleges of nursing.
While simulation laboratories for clinical nursing education are predicted to grow, budget cuts may threaten these programs. One of the ways to develop a new lab, as well as to keep an existing one on track, is to develop and regularly update a strategic plan. The process of planning not only helps keep the lab faculty and staff apprised of the challenges to be faced, but it also helps to keep senior level management engaged by reason of the need for their input and approval of the plan. The strategic planning documents drafted by those who supervised the development of the new building and Concepts Integration Labs (CILs) helped guide and orient faculty and other personnel hired to implement the plan and fulfill the vision. As the CILs strategic plan was formalized, the draft plans, including the SWOT analysis, were reviewed to provide historical perspective, stimulate discussion, and to make sure old or potential mistakes were not repeated.


Surgical management of mediastinal lesions.
Mediastinal tumors and cysts are relatively uncommon lesions requiring histologic confirmation. This retrospective study reports the experience of our department in the diagnosis and treatment of mediastinal lesions. Mediastinal lesions that were surgically treated in 200 patients aged 6-84 years, during a period of 28 years, were included in this series. Sixty patients had an apparently non-resectable lesion or lymphadenopathy of the anterior superior mediastinum. They had an anterior mediastinotomy and biopsy of the mediastinal lesion. No perioperative deaths were recorded in those patients. There were recorded 5 (8.3%) complications. Histological diagnosis was established in all patients: lymphoma (n = 21), metastatic carcinoma (n = 16), thymic lesions (n = 10), germ cell tumor (n = 3), other lesions (n = 10). The remainder 140 patients underwent a resection of the mediastinal lesion. One (0.7%) perioperative death and 21 (15%) complications were recorded. The histological diagnosis of the excised lesions was: thymic lesions (n = 60), neural tumors (n = 21), thyroid lesions (n = 14), bronchial cysts (n = 12), pericardial cysts (n = 10), germ cell tumors (n = 6), other lesions (n = 17). Our results are compared favorably with those reported in international literature. Surgery is the management of choice for patients with mediastinal lesions. It allows for establishing certain histological diagnosis and curative excision of the lesion, when it is necessary, with low operative risk.


Impact of comorbidities on the disability progression in multiple sclerosis.
Investigation of the comorbidity burden in persons with multiple sclerosis (PwMS) has become increasingly important. The aim of this study was to investigate the relationships of cardiovascular disease (CVD) comorbidities and type 2 diabetes with the disability progression. The retrospective cohort study was conducted at the Clinic of Neurology, Belgrade. The Belgrade MS population Registry, which comprises 2725 active MS cases, was used as the source of data. The mean duration of the disease was 21.6 ± 12.5 years. Expanded Disability Status Scale (EDSS) was followed in all PwMS in the Registry. In the statistical analysis, the Cox proportional hazard regression analysis and Kaplan-Meier curve were performed. Hypertension statistically significantly contributed to more rapid reaching investigated levels of irreversible disability (EDSS 4.0, 6.0, and 7.0), while the presence of any of the investigated CVD comorbidities and type 2 diabetes significantly contributed to faster reaching EDSS 4.0 and EDSS 6.0. In a multivariable model, progression index (PI) was singled out (HR = 3.171, p < .001), indicating that higher progression index (PI) was an independent predictor of CVD occurrence in MS patients. In the case of type 2 diabetes, PI (p < .001) and MS phenotype (p = .015) were statistically significant in multivariable Cox regression analysis. Our study confirms the impact of CVD comorbidities and type 2 diabetes in MS on the progression of disability as measured by EDSS in the large cohort of PwMS from the population Registry.


Buschke-Ollendorff syndrome: a 32-month-old boy with elastomas and craniosynostosis.
A 32-month-old boy with hypotonia, developmental delay, and multiple craniofacial abnormalities including craniosynostosis presented with numerous nonspecific, flesh-colored papules on his right flank. Upon biopsy, these lesions were diagnosed as elastomas. Similar skin lesions were found in the patient's younger brother. The patient's father and brother had osteopoikilotic lesions on radiography, but the patient did not have these findings. None of the reported cases to date have included craniosynostosis in association with Buschke-Ollendorff syndrome. In addition to the case findings, the report also provides a short and current review of the syndrome.


GTP induces S-phase cell-cycle arrest and inhibits DNA synthesis in K562 cells but not in normal human peripheral lymphocytes.
Since differentiation therapy is one of the promising strategies for treatment of leukemia, universal efforts have been focused on finding new differentiating agents. In that respect, we used guanosine 5'-triphosphate (GTP) to study its effects on K562 cell line. GTP, at concentrations between 25-200 microM, inhibited proliferation (3-90%) and induced 5-78% increase in benzidine-positive cells after 6-days of treatments of K562 cells. Flow cytometric analyses of glycophorine A (GPA) showed that GTP can induce expression of this marker in more mature erythroid cells in a time- and dose-dependent manner. These effects of GTP were also accompanied with inhibition of DNA synthesis (measured by [3H]-thymidine incorporation) and early S-phase cell cycle arrest by 96 h of exposure. In contrast, no detectable effects were observed when GTP administered to unstimulated human peripheral blood lymphocytes (PBL). However, GTP induced an increase in proliferation, DNA synthesis and viability of mitogen-stimulated PBL cells. In addition, growth inhibition and differentiating effects of GTP were also induced by its corresponding nucleotides GDP, GMP and guanosine (Guo). In heat-inactivated medium, where rapid degradation of GTP via extracellular nucleotidases is slow, the anti-proliferative and differentiating effects of all type of guanine nucleotides (except Guo) were significantly decreased. Moreover, adenosine, as an inhibitor of Guo transporter system, markedly reduced the GTP effects in K562 cells, suggesting that the extracellular degradation of GTP or its final conversion to Guo may account for the mechanism of GTP effects. This view is further supported by the fact that GTP and Guo are both capable of impeding the effects of mycophenolic acid. In conclusion, our data will hopefully have important impact on pharmaceutical evaluation of guanine nucleotides for leukemia treatments.


Enzymatic Electrosynthesis of Formic Acid through Carbon Dioxide Reduction in a Bioelectrochemical System: Effect of Immobilization and Carbonic Anhydrase Addition.
The enzymatic electrosynthesis of formic acid from the reduction of carbon dioxide (CO2 ) by using formate dehydrogenase (FDH) as a catalyst at the cathode in both its free and immobilized forms was studied in detail in a bioelectrochemical system (BES). The essential role of solubilizing CO2 for its conversion was also studied by adding carbonic anhydrase (CA) to the FDH enzyme in both its free and immobilized forms. FDH alone in the free form showed large variation in the reduction current [(-6.2±3.9) A m-2 ], whereas the immobilized form showed less variation [(-3.8±0.5) A m-2 ] due to increased enzyme stability. The addition of CA with FDH increased the consumption of the current in both forms due to the fact that it allowed rapid dissolution of CO2 , which made it available for the catalytic reaction with FDH. Remarkably, stable consumption of the current was observed throughout the operation if both CA and FDH were immobilized onto the electrode [(-3.9±0.2) A m-2 ]. Product formation by the immobilized enzyme was also continued for three repetitive cycles, which revealed the longevity of the enzyme after immobilization. The recyclability of NADH (NAD=nicotinamide adenine dinucleotide) was also clearly evidenced on the derivative voltammetric signature. Extension of this study for continuous and long-term operation may reveal more possibilities for the rapid capture and conversion of CO2 .


Interactive decision support in hepatic surgery.
Hepatic surgery is characterized by complicated operations with a significant peri- and postoperative risk for the patient. We developed a web-based, high-granular research database for comprehensive documentation of all relevant variables to evaluate new surgical techniques. To integrate this research system into the clinical setting, we designed an interactive decision support component. The objective is to provide relevant information for the surgeon and the patient to assess preoperatively the risk of a specific surgical procedure. Based on five established predictors of patient outcomes, the risk assessment tool searches for similar cases in the database and aggregates the information to estimate the risk for an individual patient. The physician can verify the analysis and exclude manually non-matching cases according to his expertise. The analysis is visualized by means of a Kaplan-Meier plot. To evaluate the decision support component we analyzed data on 165 patients diagnosed with hepatocellular carcinoma (period 1996-2000). The similarity search provides a two-peak distribution indicating there are groups of similar patients and singular cases which are quite different to the average. The results of the risk estimation are consistent with the observed survival data, but must be interpreted with caution because of the limited number of matching reference cases. Critical issues for the decision support system are clinical integration, a transparent and reliable knowledge base and user feedback.


High-Density Single-Layer Coating of Gold Nanoparticles onto Multiple Substrates by Using an Intrinsically Disordered Protein of α-Synuclein for Nanoapplications.
Functional graffiti of nanoparticles onto target surface is an important issue in the development of nanodevices. A general strategy has been introduced here to decorate chemically diverse substrates with gold nanoparticles (AuNPs) in the form of a close-packed single layer by using an omni-adhesive protein of α-synuclein (αS) as conjugated with the particles. Since the adsorption was highly sensitive to pH, the amino acid sequence of αS exposed from the conjugates and its conformationally disordered state capable of exhibiting structural plasticity are considered to be responsible for the single-layer coating over diverse surfaces. Merited by the simple solution-based adsorption procedure, the particles have been imprinted to various geometric shapes in 2-D and physically inaccessible surfaces of 3-D objects. The αS-encapsulated AuNPs to form a high-density single-layer coat has been employed in the development of nonvolatile memory, fule-cell, solar-cell, and cell-culture platform, where the outlying αS has played versatile roles such as a dielectric layer for charge retention, a sacrificial layer to expose AuNPs for chemical catalysis, a reaction center for silicification, and biointerface for cell attachment, respectively. Multiple utilizations of the αS-based hybrid NPs, therefore, could offer great versatility to fabricate a variety of NP-integrated advanced materials which would serve as an indispensable component for widespread applications of high-performance nanodevices.


[Engineering the enantioselectivity of biocatalysts].
Wild-type biocatalysts usually show high activity and selectivity towards their native substrates. Since non-native substrates are often used in synthetically useful biocatalytic transformations, it is necessary to engineer enzymes for improved activity, stability and selectivity (chemo-, regio- and stereoselectivity). Herein we give an overview of the recent advances in engineering the enantioselectivity of biocatalysts, with an aim to stimulate further development of this important field in China.


[Right ventricular cavernous hemangioma: a rare cardiac primary neoplasia].
Primary neoplasia of the heart is rare and often diagnosed postmortem (with a prevalence < 0.2% at postmortem examinations) due to the lack of specific clinical symptoms and signs. Among benign cardiac tumors, cavernous hemangioma has a prevalence of 2.8%. Less invasive diagnostic techniques such as transthoracic echocardiography allow for the diagnosis to be made during life with definitive surgical treatment. We report a representative case of right ventricular cavernous hemangioma, which mimicked right ventricular failure associated with systolic pulmonary flow tract obstruction. Surgical treatment was indicated for symptom severity and for the unpredictable behavior of the large neoplasm.


A comparison of prenatal drinking in two recent samples of adolescents and adults.
The drinking patterns of 124 pregnant teenagers are described and compared with those of 267 pregnant adults attending the same prenatal clinic in Pittsburgh. Adults had a significantly higher average daily volume of alcohol prior to pregnancy than adolescents, but that higher level was no longer significant during pregnancy. However, the rate of binge drinking during the first trimester was higher in the teenage sample than in the adult sample. Rates of binge drinking and heavy drinking were highest among the white teenage group. Use of marijuana and cocaine/crack decreased precipitously during pregnancy for both teenagers and adults. Tobacco use also decreased among the adults, but increased from 56% to 71% during pregnancy in the teenage sample. Based on our findings, patterns of drinking among adult pregnant women do not generalize to pregnant adolescents. Offspring of white adolescents, in particular, may be at higher risk for intermittent high peak alcohol exposure farther into the pregnancy than are offspring of older women.


The SpTransformer Gene Family (Formerly Sp185/333) in the Purple Sea Urchin and the Functional Diversity of the Anti-Pathogen rSpTransformer-E1 Protein.
The complex innate immune system of sea urchins is underpinned by several multigene families including the SpTransformer family (SpTrf; formerly Sp185/333) with estimates of ~50 members, although the family size is likely variable among individuals of Strongylocentrotus purpuratus. The genes are small with similar structure, are tightly clustered, and have several types of repeats in the second of two exons and that surround each gene. The density of repeats suggests that the genes are positioned within regions of genomic instability, which may be required to drive sequence diversification. The second exon encodes the mature protein and is composed of blocks of sequence called elements that are present in mosaics of defined element patterns and are the major source of sequence diversity. The SpTrf genes respond swiftly to immune challenge, but only a single gene is expressed per phagocyte. Many of the mRNAs appear to be edited and encode proteins with altered and/or missense sequence that are often truncated, of which some may be functional. The standard SpTrf protein structure is an N-terminal glycine-rich region, a central RGD motif, a histidine-rich region, and a C-terminal region. Function is predicted from a recombinant protein, rSpTransformer-E1 (rSpTrf-E1), which binds to Vibrio and Saccharomyces, but not to Bacillus, and binds tightly to lipopolysaccharide, β-1,3-glucan, and flagellin, but not to peptidoglycan. rSpTrf-E1 is intrinsically disordered but transforms to α helical structure in the presence of binding targets including lipopolysaccharide, which may underpin the characteristics of binding to multiple targets. SpTrf proteins associate with coelomocyte membranes, and rSpTrf-E1 binds specifically to phosphatidic acid (PA). When rSpTrf-E1 is bound to PA in liposome membranes, it induces morphological changes in liposomes that correlate with PA clustering and leakage of luminal contents, and it extracts or removes PA from the bilayer. The multitasking activities of rSpTrf-E1 infer multiple and perhaps overlapping activities for the hundreds of native SpTrf proteins that are produced by individual sea urchins. This likely generates a flexible and highly protective immune system for the sea urchin in its marine habitat that it shares with broad arrays of microbes that may be pathogens and opportunists.


Possible mechanism of pesticide toxicity-related oxidative stress leading to airway narrowing.
The study was conducted to assess the magnitude of oxidative stress and lung function abnormalities in 34 male pesticide sprayers on exposure to pesticides in mango plantations. Biochemical studies on blood antioxidant enzymes revealed an unchanged glutathione level and increased level of malondialdehyde (P < 0.001), which indicates that pesticide sprayers may have suffered from oxidative stress. Decreased acetyl-cholinesterase levels (P < 0.001) in sprayers compared to the controls suggest inhibition of cholinesterase activity. The present study shows that pesticide toxicity might lead to oxidative stress and airway narrowing resulting in decreased peak expiratory flow rate.


Non-technical skills in operating room nursing: Ethical aspects.
Non-technical skills are cognitive and interpersonal skills underpinning technical proficiency. Ethical values and respect for human dignity make operating room nurses responsible for nursing decisions that are clinically and technically sound and morally appropriate. To learn what ethical issues operating room nurses perceive as important regarding non-technical skills. Qualitative individual in-depth interviews were conducted. The interviews were analysed using Braun and Clarke's six phases for thematic analysis. Eleven experienced perioperative/operating room nurses working in an operating unit at a Norwegian university hospital. Approval was given by The Norwegian Social Science Data Service in care of the hospital's Data Protection Officer. Three main themes were found: respect and care for the patient, making the patient feel safe, and respect within the perioperative team. These features or themes, which incorporate collaboration and communication, are closely connected to patient safety. Defending the patient's dignity is part of caring for and respecting the patient. The manner in which the operating room team collaborates is important for the patient to feel safe and secure. Poor teamwork may have dire consequences. Reciprocal respect within the team includes respect for each other's tasks and responsibilities and to talk to one another in a friendly manner. Being respectful and contributing to a caring atmosphere are central ethical skills in the operating room. To patients, harmonious teamwork translates into a feeling of safety and being cared for. The nurses see respect and patient safety, and respect and reciprocal politeness among the members of the perioperative team as central ethical non-technical skills. Lack of respect influences the team negatively and is detrimental for patient safety. Good communication is an important safety measure during surgery and creates a feeling of good 'flow' within the operating room team.


A free flap system in sheep.
Five successful free flap transfers have been performed using the deep circumflex iliac artery system in sheep. The system is capable of providing cutaneous, myocutaneous, or osteomyocutaneous flaps, and details regarding these flaps are described.


Spinal cord malperfusion caused by using the segmental clamp technique during descending aortic repair for chronic type B aortic dissection.
Several effective strategies for spinal cord protection have been advocated in descending and thoracoabdominal aortic repairs. The segmental clamp technique has been known as a useful adjunct to shorten the duration of spinal cord ischemia. However, we experienced two cases of spinal cord malperfusion during segmental aortic clamping in descending aortic repair for chronic type B aortic dissection. In these patients, the intercostal arteries including the Adamkiewicz artery had originated from the false lumen. In one patient, spinal cord ischemia was initially detected as decreased motor-evoked potentials. Transesophageal echocardiography simultaneously revealed blood flow congestion in the false lumen during segmental aortic clamping and spinal cord ischemia had developed due to malperfusion of the intercostal arteries branching from the false lumen. Segmental clamping in patients with aortic dissection may not always be useful for shortening the duration of spinal cord ischemia. Transesophageal echocardiography as well as motor-evoked potentials is a useful modality for obtaining the details of intraoperative blood flow in dissecting lumens and malperfusion of the intercostal arteries related to spinal cord injury.


Massive bleeding from an ectopic lingual thyroid follicular adenoma during pregnancy.
Ectopic thyroid is a rare developmental anomaly. It can be found anywhere between the foramen cecum and the normal position of the thyroid gland. Massive bleeding from an ectopic lingual thyroid is unusual and occasionally fatal. We present a case of a 22-year-old woman who had a large mass at the base of the tongue for over 6 years. In the sixth month of pregnancy, the patient experienced massive bleeding from the tongue base mass. A thyroid scan revealed that this mass was the only functioning thyroid tissue. Because of massive bleeding and her shock status, the patient received an emergent embolization of the bilateral lingual arteries. Then the huge lingual thyroid was subsequently excised via a mandible swing approach to prevent further episodes of bleeding. Pathology analysis indicated ectopic thyroid tissue with follicular adenoma. She delivered without complications in the 36th week and had a normal baby. This case was a very rare one in our review. Although ectopic lingual thyroid usually is not managed surgically, excision of ectopic lingual thyroid can be life-saving when it is causing bleeding or airway obstruction.


Spectroscopic determination of hydrophobic adulterant tadalafil by aptasensor based ellipsometry.
Tadalafil is one of the selective phosphodiesterase type 5 inhibitors (PDE5) and serves as the active compound in drugs used for the treatment of erectile dysfunction. These PDE5 inhibitors are prescribed under medical supervision. However, cases of adulteration of dietary supplements with PDE5 inhibitors or their unapproved analogs have been reported worldwide. The presence of the PDE5 inhibitors in such supplements poses a serious health risk to consumers, particularly when combined with certain nitrate-containing drugs, as their toxic effects have not been thoroughly assessed and may result in unpredictable adverse reactions. Therefore, it is crucial to detect adulteration in these dietary supplements. However, current methods for PDE5 inhibitor detection rely on time-consuming and expensive analytical techniques, although they are sensitive. In this study, we propose an aptasensor based on ellipsometry for the detection of PDE5 inhibitors. To enhance the detection specificity for PDE5 inhibitors, we designed an aptamer with a hydrophobic pocket that incorporates a guanine base-rich region and a three-way junction. This design is particularly effective considering the poor aqueous solubility of PDE5 inhibitors. Preliminary results demonstrate that tadalafil detection in various media can be achieved within the range of 1-2000 ng/mL. The limit of detection for the active compound of tadalafil is as low as 1.82 ng/mL.


Feasibility and Efficacy of Neoadjuvant Chemotherapy without Radiotherapy for Locally Advanced Rectal Cancer.
This retrospective study explored the feasibility of neoadjuvant chemotherapy (NAC) without radiotherapy in patients with locally advanced rectal cancer (LARC). Patients with clinical stage of T3-T4 and/or N-positive LARC patients were included. We retrospectively analyzed patients' NAC-related and perioperative outcomes. The study enrolled 30 patients. mFOLFOX6 or SOX plus cetuximab was administered to 12 patients with the wild-type RAS gene and FOLFOXIRI or SOXIRI to 18 patients with mutant-type RAS. The NAC completion rate was 90.0%. All patients underwent total mesorectal excision, and 29 patients underwent combined bilateral lateral lymph node dissection. The R0 operation rate was 90.0%. Although the postoperative complication rate was 40%, no complications were associated with NAC. The response rate of NAC and the proportion of histological anti-tumor effect grade ≥ 2 were 56.7% and 46.7%, respectively. NAC was considered to be a safe, feasible treatment option for LARC.