Cancer cell-specific oligopeptides selected by an integrated microfluidic system from a phage display library for ovarian cancer diagnosis.
Ovarian cancer is one of the leading causes of female mortality worldwide. Unfortunately, there are currently few high-specificity candidate oligopeptide targeting agents that can be used for early diagnosis of this cancer. It has been suggested that cancer-specific oligopeptides could be screened from a phage display library. However, conventional methods are tedious, labor-intensive, and time consuming. Therefore, a novel, integrated microfluidic system was developed to automate the entire screening process for ovarian cancer cell-specific oligopeptides. An oligopeptide screened with microfluidic chip-based technique was demonstrated to have high affinity to ovarian cancer cells and demonstrated relatively low binding to other cancer cells, indicating a high specificity. Furthermore, the developed method consumed relatively low volumes of samples and reagents; only 70 μL of reactant was used within the whole experimental process. Each panning process was also significantly shortened to only 7.5 hours. Therefore, the screened oligopeptide could be used to isolate ovarian cancer cells in a rapid manner, thus greatly expediting the diagnosis and its application as oligopeptide targeting agent for theranostics of this cancer.


Fast-track method in cardiac surgery: evaluation of risks and benefits of continuous administration technique.
Fast-track is a method proposed to decrease medical costs through the reduction of patients' length of stay in the hospital. This study was carried out to assess the risks and benefits of conducting the fast-track method in cardiac anaesthesia and to evaluate the role of continuous infusion of short-acting anaesthetics in a successful fast-track protocol. 100 cases were divided into two groups. In the fast-track group, fentanyl and propofol infusions were started at induction time and atracurium one hour later. No bolus drug was administered during the operation. Fentanyl infusion was continued up to 12 hours after surgery. The conventional extubation group received fentanyl and pancuronium as bolus doses. The two groups were evaluated for time of alertness and extubation in the intensive care unit, total analgesic dosage administered during the 24 hours after operation, arterial blood gas and peripheral saturation of oxygen before and after extubation. Time period between intensive care unit admission and alertness was significantly different in the fast-track (1.3 hours) and control (3.3 hours) groups (p-value is less than 0.001) as well as total time of intubation in the intensive care unit (4.3 hours vs. 7 hours) (p-value is less than 0.001). No patient of the fast-track group experienced low pressure of arterial oxygen, low saturation of arterial oxygen, high pressure of arterial carbon dioxide or need for reintubation in the first 24 hours after surgery. Continuous infusion of drugs in the fast-track method facilitates earlier extubation. It maintains continuous sedation and analgesia without increasing respiratory complications.


HIV-risk practices among homeless and low-income housed mothers.
Knowledge of human immunodeficiency virus (HIV) and its risk behaviors have not been systematically studied in homeless mothers. The identification of the factors associated with HIV-risk practices will guide interventions for low-income housed and homeless women. We interviewed 220 homeless and 216 low-income housed mothers living in Worcester, Massachusetts, to gather information on demographic, psychosocial , and HIV-risk practice characteristics. We used standardized instruments and questions drawn from national surveys. The primary study outcome was high HIV-risk behavior. Although homeless mothers were more likely than low-income housed mothers to report first sexual contact at an early age, multiple partners during the last 6 months, and a history of intravenous drug use, homelessness was not associated with high HIV-risk practices. Both homeless and low-income housed mothers demonstrated misconceptions about HIV transmission through casual contact. Among high-risk women, approximately 75% perceived themselves as having low or no risk for contracting HIV. A history of childhood victimization, adult partner violence, or both placed women at a significantly increased likelihood of high HIV-risk practices. African American race, knowledge about HIV, and self-perception of risk were also significantly associated with high-risk practices. Homeless mothers are a subgroup of poor women at high risk for HIV and should be targeted for preventive interventions. In addition, there are potentially modifiable factors associated with HIV-risk practices in both low-income housed and homeless mothers that should be directly addressed.


Factors influencing women in seeking help from a health care professional on self discovery of a breast symptom, in an Irish context.
To identify the extent of delay and the factors influencing women in seeking help from a health care professional on self discovery of a breast symptom, in an Irish context. Breast cancer is the most common malignancy among women in the developed world. In Ireland, 2700 women are diagnosed with breast cancer and over 900 die from it annually. A longer delay in presenting with breast symptoms is associated with a lower rate of survival from breast cancer. However, many women wait for longer than three months before presenting to a health care professional on self discovery of a breast symptom. A quantitative correlational design was used. Data were collected using the 'Women's help seeking for breast symptoms' questionnaire. Women were recruited in the breast clinic prior to their visit with the consultant. A total of 100 women participated, 99 of whom fully completed the questionnaire. Mean age was 40 years. It was found that 72.7% (n = 73) of women visited their GP within one month, 14.1% (n = 14) within one to three months and 10% (n = 12) after three months. Delay time was significantly related to women's knowledge and beliefs and social issues. Conversely, help seeking also correlated to women's knowledge and beliefs about the symptom and the anxiety surrounding the initial symptom discovery period. Despite breast health promotion campaigns, many women delay for one month or more, in seeking help from a health care professional for self discovered breast symptoms. Prolonged delay has potential to impact on survival from breast cancer. This highlights the need for continued education and breast health promotion for women. Health care professionals need to be aware of possible reasons for delay in seeking help for self discovered breast symptoms and explore new ways to address these barriers.


Hindered nanoparticle diffusion and void accessibility in a three-dimensional porous medium.
The inherent pore-scale heterogeneity of many natural and synthetic porous materials can make it difficult to model and predict porous transport because the underlying microscopic processes are often poorly understood. Here we present the results of single-particle tracking experiments in which we followed the pore-scale diffusion of individual nanoparticles, deep within a three-dimensional porous material of moderate porosity. We observed significant hydrodynamic damping of particle motion at subpore length scales, resulting in heterogeneous and spatially dependent mobility. The accessibility of the void space was strongly dependent on particle size, and related to the heterogeneous hydrodynamics. Our results suggest that pore-scale diffusion is more heterogeneous and volume accessibility more limited than previously expected. The method demonstrated here will enable studies of a broad new class of materials including porous polymers of technological interest.


Vegetarian diet and incidence of total, ischemic, and hemorrhagic stroke in 2 cohorts in Taiwan.
To determine how a vegetarian diet affects stroke incidence in 2 prospective cohorts and to explore whether the association is modified by dietary vitamin B12 intake. Participants without stroke in the Tzu Chi Health Study (cohort 1, n = 5,050, recruited in 2007-2009) and the Tzu Chi Vegetarian Study (cohort 2, n = 8,302, recruited in 2005) were followed until the end of 2014. Diet was assessed through food frequency questionnaires in both cohorts at baseline. Stroke events and baseline comorbidities were identified through the National Health Insurance Research Database. A subgroup of 1,528 participants in cohort 1 were assessed for serum homocysteine, vitamin B12, and folate. Associations between vegetarian diet and stroke incidences were estimated by Cox regression with age as time scale, adjusted for sex, education, smoking, alcohol, physical activities, body mass index (only in cohort 1), hypertension, diabetes, dyslipidemia, and ischemic heart diseases. Vegetarians had lower serum vitamin B12 and higher folate and homocysteine than nonvegetarians. In cohort 1, 54 events occurred in 30,797 person-years follow-up. Vegetarians (vs nonvegetarians) experienced lower risk of ischemic stroke (hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.08-0.88). In cohort 2, 121 events occurred in 76,797 person-years follow-up. Vegetarians (vs nonvegetarians) experienced lower risk of overall stroke (HR, 0.52; 95% CI, 0.33-0.82), ischemic stroke (HR, 0.41; 95% CI, 0.19-0.88), and hemorrhagic stroke (HR, 034; 95% CI, 0.12-1.00). Our explorative analysis showed that vitamin B12 intake may modify the association between vegetarian diet and overall stroke (p interaction = 0.046). Taiwanese vegetarian diet is associated with a lower risk of ischemic and hemorrhagic strokes.


Quantification of sulforaphane mercapturic acid pathway conjugates in human urine by high-performance liquid chromatography and isotope-dilution tandem mass spectrometry.
We report validation of the first high-pressure liquid chromatography isotope-dilution mass spectrometry method to measure sulforaphane (SFN) and its glutathione-derived conjugates in human urine. As epidemiological evidence continues to mount that the consumption of a diet rich in cruciferous vegetables may reduce the risk of certain cancers, the development of analytical methodologies to accurately measure isothiocyanates (ITCs) and their subsequent metabolic products becomes paramount. SFN, the principal ITC produced by broccoli, is an effective chemopreventive agent with multiple modes of action. SFN and SFN conjugates have often been measured collectively utilizing a cyclocondensation assay with 1,2-benzenedithiol. More recently, some of the major SFN conjugates have been determined using mass spectrometry. Here, triple-quadrupole mass spectrometry has been coupled with the use of stable isotope-labeled internal standards of D8-SFN and all four D8-SFN mercapturic acid pathway conjugates to provide an accurate, precise, sensitive, and specific method for analysis of these compounds. Using urine samples collected during an earlier intervention with broccoli sprouts, the concentrations of SFN, SFN-cysteine, and the mercapturic acid SFN- N-acetylcysteine were sufficiently high such that as little as 50 nL of urine was required for analysis. Although each study participant received an equivalent dose of broccoli sprout preparation, the interindividual conversion of the precursor glucosinolate to SFN varied over 100-fold. These 98 urines provided an ideal sample set for examining the robustness of the assay. The mean urinary concentrations +/- standard deviations in overnight voids following ingestion of the first dose were 4.7 +/- 5.1, 0.03 +/- 0.05, 0.06 +/- 0.06, 18 +/- 15, and 42 +/- 23 nmol/mg creatinine for SFN, SFN-glutathione, SFN-cysteine-glycine, SFN-cysteine, and SFN- N-acetylcysteine, respectively. This method determines SFN and all four SFN glutathione-derived metabolites with minimal sample preparation and will be extremely useful in understanding the role of SFN-rich foods in preventing cancer and other chronic diseases.


Changes in ionic movements across rabbit polymorphonuclear leukocyte membranes during lysosomal enzyme release. Possible ionic basis for lysosomal enzyme release.
Changes in the movements of Na+, K+, and Ca+2 across rabbit neutrophils under conditions of lysosomal enzyme release have been studied. We have found that in the presence of cytochalasin B, the chemotactic factor formyl methionyl leucyl phenylalanine (FMLP) induces within 30 s large enhancements in the influxes of both 22Na+ and 45Ca+2 and an increase in the cellular pool of exchangeable calcium. The magnitude of the changes induced by cytochalasin B and FMLP exceeds that induced by FMLP or cytochalasin B alone, and cannot be explained on the basis of an additive effect of the two agents. However, these compounds either separately or together produce much smaller enhancements in 45Ca efflux. The divalent cation ionophore A23187 also produces a rapid and large increase in the influxes of both 22Na and 45Ca+2 in the presence and absence of cytochalasin B. We have also found an excellent correlation between calcium influx and lysosomal enzyme release. 42K influx is not significantly affected by any of these compounds. On the other hand, a large and rapid increase of 42K efflux is observed under conditions which give rise to lysosomal enzyme release. A flow diagram of the events that are thought to accompany the stimulation of polymorphonuclear leukocytes (PMNs) by chemotactic or degranulating stimuli is presented.


A meta-analysis of hypnosis for chronic pain problems: a comparison between hypnosis, standard care, and other psychological interventions.
Hypnosis is regarded as an effective treatment for psychological and physical ailments. However, its efficacy as a strategy for managing chronic pain has not been assessed through meta-analytical methods. The objective of the current study was to conduct a meta-analysis to assess the efficacy of hypnosis for managing chronic pain. When compared with standard care, hypnosis provided moderate treatment benefit. Hypnosis also showed a moderate superior effect as compared to other psychological interventions for a nonheadache group. The results suggest that hypnosis is efficacious for managing chronic pain. Given that large heterogeneity among the included studies was identified, the nature of hypnosis treatment is further discussed.


Microsatellite instability and mismatch repair protein defects in ovarian epithelial neoplasms in patients 50 years of age and younger.
Ovarian malignancies occurring in the setting of hereditary nonpolyposis colorectal carcinoma syndrome typically present in young women, often as the first or "sentinel" cancer, but the frequency of microsatellite instability (MSI) and mismatch repair (MMR) defects in ovarian surface epithelial malignancies in women <or=50 years of age is neither well known nor well tested. Fifty-two ovarian surface epithelial carcinomas, including 4 with synchronous endometrial carcinomas, were identified in patients 50 years of age or younger and evaluated for evidence of MSI and MMR protein deficiency. Each case was tested for MSI by multiplex polymerase chain reaction amplification of the National Cancer Institute reference panel (BAT25, BAT26, D2S123, D5S346, and D17S250) and deficiency of MMR protein expression by immunohistochemistry (MLH1, MSH2, MSH6, and PMS2). MMR protein expression and MSI (in a subset of cases) were also evaluated in 50 unselected ovarian serous tumors of low malignant potential , a tumor common in younger women. Defects in MMR were detected in 5 of 52 (10%) ovarian carcinomas by at least 1 testing method, including 2 of 4 (50%) ovarian cancers presenting with synchronous endometrial cancer. Three of the 5 (60%) ovarian carcinomas were clear cell carcinomas (17% of all pure clear cell carcinomas) and the remaining 2 were high-grade carcinomas with endometrioid and mixed histology. Loss of MSH2 and MSH6 was detected in all of the affected clear cell carcinomas and a synchronous endometrial cancer with endometrioid histology. Loss of 1 or more MMR proteins was initially noted in 10/50 ovarian serous tumors of low malignant potential on tissue microarray, but further testing on full tissue sections showed intact protein expression and microsatellite stability in all informative cases. This study demonstrates a 10% rate of MMR-deficient ovarian cancer in women <or=50 years of age. MMR-deficient ovarian cancer is frequently associated with loss of expression of MSH2 and MSH6 proteins and clear cell histology. The occurrence of MMR inactivation in a significant proportion of ovarian clear cell carcinomas (17% in this study) suggests that this tumor may warrant targeted testing in women <or=50 years of age.


Intercessory Rote Prayer, Life Longevity and the Mortality of Roman Catholic Bishops: An Exploratory Study.
Based on a computational analysis of a large dataset, this study explores if there is a significant longevity effect of intercessory prayer for a named individual's well-being, if he receives a very high number of prayers per annum for an extended period. We relied on an observational cohort study, based on data from 1988 to 2018, including 857 Roman Catholic bishops, 500 Catholic priests, and 3038 male academics from six countries. We measured the covariance of the mean length of life, controlled for nationality. It was found that there is a main effect for occupation F(2, 4391) = 4.07, p = 0.017, ηp2 = 0.002, with pairwise comparisons indicating significant differences between the mean life duration of bishops (M = 30,489) and of priests (M = 29,894), but none between the academic teachers (M = 30,147) and either of the other groups. A comparison analysis between bishops from the largest and the smallest dioceses showed no significant difference t(67.31) = 1.61, p = 0.11. The first analysis proved that bishops live longer than priests, but due to a marginal effect size this result should be treated with caution. No difference was found between the mean length of life of bishops from the largest and the smallest dioceses.


The mediating role of work-related perceptions in the relationship between empathy and self-perceived clinical performance of residents in China: A multi-center cross-sectional study.
This study aimed to describe the association between empathy and residents' clinical performance and investigate whether work-related perception mediates this relationship. A multi-center cross-sectional study was conducted, including 1160 residents from 10 cities in Liaoning Province between March and October 2020. The participants completed various self-reported questionnaires regarding demographic characteristics, work-related perceptions, self-perceived clinical performance, and empathy. The relationships among empathy, work-related perception, and self-perceived clinical performance were examined using a structural equation model (SEM). Of the 1160 residents, 961 (82.8 %) completed the questionnaires. The SEM path analysis showed that the direct effect of empathy on self-perceived clinical performance was significant and positive (β = 0.34, P < 0.001). There existed significant effects of empathy on work-related perception (β = 0.26, P < 0.001) and work-related perception on performance (β = 0.31, P < 0.001). The path coefficients of empathy concerning self-perceived clinical performance decreased significantly (β = 0.26, P < 0.001) when work-related perception was modeled as a mediator. The bias-corrected and accelerated bootstrap test revealed that work-related perception significantly mediated the relationship between empathy and self-perceived clinical performance (a*b = 0.08, BCa 95 % CI: 0.05-0.13). However, the correlation between the sub-scales of empathy and the items of self-perceived clinical performance was not substantial, even if most of them were statistically significant. The final SEM produced a good fit to the sample data, with CMIN/DF = 2.07 (P < 0.001), CFI = 0.99, GFI = 0.99, AGFI = 0.98, TLI = 0.98, NFI = 0.97, RMSEA (90 % CI) = 0.033 (0.017, 0.049), and SRMR = 0.024. Empathy might significantly affect self-perceived clinical performance both directly and indirectly through the mediating role of work-related perception. Efforts to improve clinical performance among residents might benefit from interventions for cultivating empathy and practices for improving work-related perceptions of residents.


Hederagenin Upregulates PTPN1 Expression in Aβ-Stimulated Neuronal Cells, Exerting Anti-Oxidative Stress and Anti-Apoptotic Activities.
Alzheimer's disease (AD) is a prevalently neurodegenerative disease characterized by neuronal damage which is associated with amyloid-β (Aβ) accumulation. Hederagenin is a triterpenoid saponin, exerting anti-apoptotic, anti-oxidative, anti-inflammatory, anti-tumoral, and neuroprotective activities. However, its role in AD progression is still obscure. The aim of this study was to explore the influences of hederagenin on Aβ-caused neuronal injury in vitro. Neuronal cells were treated with Aβ25-35 (Aβ) to establish a cellular model of AD. Cell viability was assessed using cell counting kit-8 (CCK-8). Oxidative stress was evaluated by detecting reactive oxygen species (ROS) generation and superoxide dismutase (SOD) activity. Apoptosis was investigated using TUNEL staining and caspase-3 activity assays. Protein tyrosine phosphatase nonreceptor type 1 (PTPN1) was screened by bioinformatics analysis. Protein levels of PTPN1 and protein kinase B (Akt) were measured by western blotting. Hederagenin (2.5, 5, and 10 μM) alone did not affect viability of neuronal cells, but relieved Aβ-induced viability reduction. Hederagenin mitigated Aβ-induced increase in ROS accumulation and decrease in SOD activity. Hederagenin attenuated Aβ-induced increase in apoptotic rate and caspase-3 activity. PTPN1 was screened as a target of hederagenin against AD by bioinformatics analysis. Hederagenin treatment resisted Aβ-induced decrease in PTPN1 mRNA and protein levels in neuronal cells. PTPN1 silencing attenuated the suppressive functions of hederagenin in Aβ-stimulated oxidative stress and apoptosis. Hederagenin mitigated Aβ-induced Akt signaling inactivation by upregulating PTPN1 expression. In conclusion, hederagenin attenuates oxidative stress and apoptosis in neuronal cells stimulated with Aβ by promoting PTPN1/Akt signaling activation.


[The viability of fungal species from the genera Penicillium and Botrytis in sea and river water contaminated by liquid swine manure].
The growth ability of certain types of fungi Penicillium and Botrytis has been studied in marine and river water, contaminated by liquid swine manure (LSM). It has been found out, that addition of LSM stops P. lilacinum and B. bassiana growth. While the growth of the other types of fungi P. P. Penicillium and Botrytis, that were studied in the marine and river water, contaminated by LSM, may continue provided the temperature is favourable. The growth is discontinued at water temperature 4-6 degrees C and lower.


The true cost of the economic crisis on psychological well-being: a review.
The recent economic crisis has led to many negative consequences, not the least having to do with the mental health and well-being of the populations involved. Although some researchers say it is still too early to speak about a relationship between the economic crisis and a rise in mental health problems resulting in suicides, there is solid evidence for the existence of such a relationship. However, several moderating or mediating mechanisms can also play a role. The main reactions of most policy makers to the economic crisis are (severe) austerity measures. These measures seem to have, however, a detrimental effect on the mental health of the population: Just when people have the highest need for mental help, cost-cutting measures in the health care sector lead to a (substantial) drop in the supply of services for the prevention, early detection, and cure of mental health problems. Policy makers should support moderating mechanisms such as financial and psychological coping and acculturation and the role of primary health care workers in the early detection of suicidal thoughts, suicide attempts, and suicide in times of economic recession. Several examples show that the countries best off regarding the mental health of their populations during the economic crisis are those countries with the strongest social safety net. Therefore, instead of cutting back on health care and social welfare measures, policy makers should in the future invest even more in social protection measures during economic crises.


An Important Finding of Systemic Aspergillosis: Skin Involvement and Amphotericin B Resistance in an Adolescent.
Invasive aspergillosis is a life-threatening infectious complication in immunocompromised patients, especially with malignancy, and in some cases, it causes extensive tissue destruction and subsequent systemic illness, leading to multiorgan failure and death. Skin involvement and amphotericin B resistance are very rare findings of aspergillosis. Herein, we report the case of a primary hemophagocytic syndrome patient who developed subcutaneous nodules in the 3(rd) month of bone marrow transplantation from which Aspergillus fumigatus was cultivated despite the fact that she was under antifungal therapy. In immunocompromised patients with prolonged fever, atypical presentations of invasive mycosis should be kept in mind, and early appropriate therapy should be initiated promptly to decrease morbidity and mortality.


Serosurvey of Anti-Toxoplasma gondii Antibodies in Homeless Persons of São Paulo City, Southeastern Brazil.
Seroprevalence of Toxoplasma gondii has been extensively studied in a variety of different human populations. However, no study has focused on homeless populations. Accordingly, the present study aimed to assess the seroprevalence of anti-T. gondii antibodies and the risk factors associated in homeless persons from homeless shelter of São Paulo city, southeastern Brazil. In addition, anti-HIV antibodies and associated risk of T. gondii and HIV coinfection have been evaluated. Anti-T. gondii antibodies were detected by indirect fluorescent antibody test. In addition, anti-HIV levels were tested by chemiluminescence enzyme immunoassay, with positive samples confirmed by rapid immunoblot assay. Overall, IgG anti-T. gondii seropositivity was found in 43/120 (35.8%) homeless persons, with endpoint titers varying from 16 to 1,024. The only two pregnant women tested were negative for IgM by chemiluminescence enzyme immunoassay, with normal parturition and clinically healthy newborns in both cases. There were no statistical differences in the risk factors for anti-T. gondii serology (p > 0.05). Anti-HIV seropositivity was found in 2/120 (1.7%) homeless persons, confirmed as HIV-1. One HIV seropositive individual was also sero-reactive to IgG anti-T. gondii, and both were negative to IgM anti-T. gondii. This is the first study that reports the serosurvey of T. gondii in homeless persons worldwide. Despite the limited sample size available in the present study, our findings have shown that the prevalence of anti-T. gondii antibodies in homeless persons herein was lower than the general population, probably due to homeless diet habit of eating mainly processed food intake. No statistical differences were found regarding risk factors for anti-T. gondii exposure in homeless persons. Future studies should be conducted to fully establish risk factors for anti-T. gondii exposure in homeless persons.


Primary tumors of the external and middle ear. Benign and malignant glandular neoplasms.
Glandular neoplasms represented 14% of primary tumors of the external and middle ear at the University of Minnesota. Although the collective term "ceruminoma" has been used in the past, four distinctive histopathologic patterns were recognized among our 12 cases: adenoma (four cases), pleomorphic adenoma (one case), adenoid cystic carcinoma (two cases) and adenocarcinoma (five cases). The prognosis correlated with these subgroups. A thorough review of the English literature also tended to support the rationale for the subclassification of so-called ceruminomas. The prevailing histogenetic view is that these tumors are derived from the modified apocrine glands of the auditory canal, the ceruminous glands. In some instances, these tumors may originate from ectopic salivary gland tissue.


Arthropod Bites and Stings Treated in Emergency Departments: Recent Trends and Correlates.
Despite increasing health effects of arthropod bites and associated costs, research on their frequency is limited, especially at the population level. The aim of this study was to estimate the prevalence, correlates, and recent trends in visits to US emergency departments related to arthropod bites and stings. The prevalence of arthropod bites, including information regarding location of the bite, was calculated for years 2010 through 2014 using data from the Healthcare Cost and Utilization Project Nationwide Emergency Department Sample. Sex- and age-stratified multivariate logistic regression analyses were conducted with "arthropod bite" as the dependent variable and patient and hospital characteristics as independent variables. Overall, there were significant increases in bites over the study period with higher rates of bites in the summer months (June-August), especially among children. Individuals who seek treatment for arthropod bites in the emergency department are more likely to reside in zip codes with lower median household income and to be without insurance coverage or with Medicaid rather than private insurance. The cost of care related to arthropod bites increased approximately 40% over the study period. These results provide updated surveillance on the prevalence and correlates of arthropod bites and stings in the US population.


Intellectual disability, challenging behaviour and cost in care accommodation: what are the links?
The paper examines the links between degree of intellectual disability, challenging behaviour, service utilisation and cost for a group of people with intellectual disabilities living in care accommodation in England. A cross-sectional survey was conducted of people with intellectual disabilities, identified via provider organisations, with supplementary collection of costs data. Multivariate analyses of cost variations were carried out for 930 adults with intellectual disabilities. There were strong, nonlinear, interdependent links between degree of intellectual disability, behaviour, service use and costs. Higher costs were associated with more severe intellectual disabilities and more challenging behaviour. Sector and scale of residence also influenced cost in quite complex ways. Access to and use of services by people with intellectual disabilities were not always appropriately linked to perceived or actual needs. Policy makers and local commissioning agencies need to explore the sources of cost variation between individuals, sectors and types of accommodation in order to achieve national policy objectives on quality, choice, independence and inclusion.


Some features of the reaction of intracellular bacteriophages T1 to UV irradiation.
The reaction of complexes pf phage T1-cells of E. coli B or E. coli Bs-1 to UV irradiation was investigated. The complexes were irradiated at various stage of infection, and their survival, extent of Hcr and Phr, were evaluated. It was found that the UV resistance of phage DNA in the second half of the latent period fluctuates. Hcr after UV exposure at these stages of infection operates in a small volume. The ability of intracellular phage to photoreactivate when cells of E. coli B were infected is constant after irradiation at many stages of infection, except the early ones. In the complexes of phage T1-bacteria of E. coli Bs-1 this ability declines while infection is promoted. The daughter phage particles released from UV irradiated complexes undergo Phr and Hcr only after irradiation at the late stages of infection. This was not the cases when complexes of phage-bacteria were irradiated during the first half of the latent period. A possible tole of UV-damaged phage DNA in propagation of infection and in maturation of phage particles is discussed.


Basigin expression and regulation in mouse ovary during the sexual maturation and development of corpus luteum.
Basigin is a highly glycosylated transmembrane protein belonging to the immunoglobulin superfamily. Basigin-deficient male mice are azoospermic. The majority of basigin null embryos die around the time of implantation. However, basigin expression and regulation in mouse ovary is still unknown. The aim of this study was to investigate basigin expression in mouse ovary during sexual maturation, gonadotropin treatment, and luteal development by in situ hybridization and immunohistochemistry. Both basigin mRNA and immunostaining were not detected in the granulosa cells of preantral follicles until day 20 after birth. On day 30 after birth, basigin immunostaining dropped to a basal level, while basigin mRNA was still at a high level. Basigin expression was strongly induced by equine chorionic gonadotropin (eCG) treatment at 4 and 8 hr post-eCG injection. Both basigin immunostaining and mRNA signals were strongly observed in the corpus luteum on days 2 and 3 post-hCG injection. However, no basigin expression was detected from days 6 to 15 post-hCG injection. In conclusion, our data suggest that basigin may play a role during the mouse follicle development and corpus luteum formation.


The welfare implications of public healthcare financing: a macro-micro simulation analysis of Uganda.
Studies on global health and development suggest that there is a strong correlation between the burden of disease and a country's level of income. Poorer countries tend to suffer more deaths from preventable causes such as communicable, maternal, perinatal and nutritional conditions, compared with high-income countries. In low-income countries, the government health expenditure share in the general government budget is low and out-of-pocket payments for healthcare relatively high. They also rely heavily on external resources for health funding, yet sustainability of external resource flows is not guaranteed. This article explores increasing public healthcare funding from domestic resources mobilization, and evaluates the impact of measures to achieve this on sectoral growth and poverty reduction rates in Uganda using a dynamic computable general equilibrium model. This article shows that increasing the government health budget share, facilitates expanded healthcare services, improved population health, higher sectoral growth and reduced poverty. The agricultural sector is predicted to post the highest growth when compared with services and industry sectors under both domestic taxation and aid funding scenarios, while national poverty is predicted to decline from 31 to 12% of the population by 2020. This article demonstrates that the most effective measure is to frontload investment in healthcare and generate additional domestic funding for health from a household tax earmarked for health.


Structure of the cytoplasmic beta subunit-T1 assembly of voltage-dependent K+ channels.
The structure of the cytoplasmic assembly of voltage-dependent K+ channels was solved by x-ray crystallography at 2.1 angstrom resolution. The assembly includes the cytoplasmic (T1) domain of the integral membrane alpha subunit together with the oxidoreductase beta subunit in a fourfold symmetric T1(4)beta4 complex. An electrophysiological assay showed that this complex is oriented with four T1 domains facing the transmembrane pore and four beta subunits facing the cytoplasm. The transmembrane pore communicates with the cytoplasm through lateral, negatively charged openings above the T1(4)beta4 complex. The inactivation peptides of voltage-dependent K(+) channels reach their site of action by entering these openings.


Chemical investigation and quality of urban dew collections with dust precipitates.
The quality and chemical composition of urban dew collections with dust precipitates without pre-cleaning of the collecting surface WSF (white standard foil) were investigated for 16 out of 20 collected samples with collected volumes ranging from 22 to 230 ml. The collection period was from March to July 2015 at an urban area, Jubaiha, which is located in the northern part of the capital city Amman, Jordan. The obtained results indicated the predominance of Ca2+ and SO42- ions (ratio 2.2:1) that originated from Saharan soil dust; where the collected samples were alkaline (mean pH = 7.35) with high mineralization (429.22 mg/L) exceeding the previously reported dew values in Amman-Jordan. A relocation of NaCl and to a less extent Mg2+ from sea to land by Saharan wind is indicated by the percent sea-salt fraction calculations (over 100 and 52, respectively). The collected samples exhibited high total organic carbon (TOC) values ranging from 11.86 to 74.60 mg/L, presence of particulate settled material with turbidity ranging from 20.10 to 520.00 NTU, and presence of undesired elements like boron (mean = 1.48 mg/L) that made it different in properties from other dew water collections at clean surfaces, and exceeding the standard limits for drinking water for these parameters set by Jordanian Drinking Water standards (JS286/2015)/WHO standard. The quality of this water is more close to that for raw or agricultural water but if it is meant to be used as potable source of water, at least sand and activated charcoal filters are needed to purify it.


Bronchogenic cyst invading right atrium in a 5-year-old.
Primary bronchogenic cysts of cardiac origin or extension are rare. We report here on a 5-year-old girl with a bronchogenic cyst with a diameter of 5.0 x 4.5 x 4.5 cm extending to the right atrial wall. Tumor enucleation and resection of the cyst together with the invaded right atrial wall was performed through a right posterolateral thoracotomy and an opening in the lateral pericardium. Resection of intrapericardial bronchogenic cysts is possible, although extensive invasion of cardiac structures may necessitate the use of cardiopulmonary bypass through a sternotomy.


Endovascular treatment of abdominal aortic aneurysms: lessons learned.
The authors offer an overview of their 20-year involvement in the development of an endovascular graft for abdominal aortic aneurysm exclusion. Clinical experience gained throughout 6 years of clinical evaluation are reviewed, along with observations and insights on preoperative assessment, implantation techniques, and complications.


The puzzle of the Krebs citric acid cycle: assembling the pieces of chemically feasible reactions, and opportunism in the design of metabolic pathways during evolution.
The evolutionary origin of the Krebs citric acid cycle has been for a long time a model case in the understanding of the origin and evolution of metabolic pathways: How can the emergence of such a complex pathway be explained? A number of speculative studies have been carried out that have reached the conclusion that the Krebs cycle evolved from pathways for amino acid biosynthesis, but many important questions remain open: Why and how did the full pathway emerge from there? Are other alternative routes for the same purpose possible? Are they better or worse? Have they had any opportunity to be developed in cellular metabolism evolution? We have analyzed the Krebs cycle as a problem of chemical design to oxidize acetate yielding reduction equivalents to the respiratory chain to make ATP. Our analysis demonstrates that although there are several different chemical solutions to this problem, the design of this metabolic pathway as it occurs in living cells is the best chemical solution: It has the least possible number of steps and it also has the greatest ATP yielding. Study of the evolutionary possibilities of each one-taking the available material to build new pathways-demonstrates that the emergence of the Krebs cycle has been a typical case of opportunism in molecular evolution. Our analysis proves, therefore, that the role of opportunism in evolution has converted a problem of several possible chemical solutions into a single-solution problem, with the actual Krebs cycle demonstrated to be the best possible chemical design. Our results also allow us to derive the rules under which metabolic pathways emerged during the origin of life.


Novel airway smooth muscle-mast cell interactions and a role for the TRPV4-ATP axis in non-atopic asthma.
Mast cell-airway smooth muscle (ASM) interactions play a major role in the immunoglobulin (Ig)E- dependent bronchoconstriction seen in asthma but less is known about IgE-independent mechanisms of mast cell activation. Transient receptor potential cation channel, subfamily V, member 4 (TRPV4) activation causes contraction of human ASM via the release of cysteinyl leukotrienes (cysLTs) but the mechanism is unknown. The objective of the present study was to investigate a role for IgE-independent, mast cell-ASM interaction in TRPV4-induced bronchospasm.Bronchoconstriction was measured in anaesthetised guinea pigs and contraction of human and guinea-pig airway tissue assessed using isometric tension measurements. Increases in intracellular [Ca2+] were imaged using the Ca2+-sensitive dye FURA2, and time-lapse ptychography was utilised as a surrogate for contraction of ASM cells.The TRPV4 agonist GSK1016790A caused contraction in vivo in the guinea pig, and in human and guinea-pig tracheal tissue, which was inhibited by the TRPV4 antagonist GSK2193874. GSK1016790A increased [Ca2+]i and released ATP in human ASM cells without causing contraction. TRPV4 and ATP evoked contraction in isolated tracheal tissue but co-culture experiments indicated a requirement for human lung mast cells. Expression profiling and pharmacological studies demonstrated that mast cell activation was dependent upon ATP activating the P2X4 receptor. Trypsin was shown to evoke contraction of tracheal tissue via activation of PAR-2-TRPV4-ATP-cysLT axis indicating the potential disease relevance of this signalling pathway.TRPV4 activation increases [Ca2+]i and releases ATP from ASM cells triggering P2X4-dependent release of cysLTs from mast cells resulting in ASM contraction. This study delineates a novel mast cell-ASM interaction and TRPV4 as a driver of IgE-independent mast cell-dependent bronchospasm.


Patients with multimorbidity and their experiences with the healthcare process: a scoping review.
The number of patients with multimorbidity (two or more conditions) is increasing. Observational research has shown that having multiple health problems is associated with poorer outcomes in terms of health, quality of care, and costs. Thus, it is imperative to understand how patients with multimorbidity experience their healthcare process. Insight into patient experiences can be used to tailor healthcare provision specifically to the needs of patients with multimorbidity. To synthesize self-reported experiences with the healthcare process of patients with multimorbidity, and identify overarching themes. A scoping literature review that evaluates both qualitative and quantitative studies published in PubMed, Embase, MEDLINE, and PsycINFO. No restrictions were applied to healthcare setting or year of publication. Studies were included if they reported experiences with the healthcare process of patients with multimorbidity. Patient experiences were extracted and subjected to thematic analysis (interpretative), which revealed overarching themes by mapping their interrelatedness. Overall, 22 empirical studies reported experiences of patients with multimorbidity. Thematic analysis identified 12 themes within these studies. The key overarching theme was the experience of a lack of holistic care. Patients also experienced insufficient guidance from healthcare providers. Patients also perceived system-related issues such as problems stemming from poor professional-to-professional communication. Patients with multimorbidity experience a range of system- and professional-related issues with healthcare delivery. This overview illustrates the diversity of aspects that should be considered in designing healthcare services for patients with multimorbidity.


Successful Management of Intraoperative Acute Bilateral Pulmonary Embolism in a High Grade Astrocytoma Patient.
BACKGROUND Intraoperative pulmonary embolism (PE) is a rare life-threatening complication in patients undergoing surgical intervention. Generally, cancer patients have a higher risk for developing this complication. Unfortunately, there is no standard procedure for its management. CASE REPORT We report the case of a 39-year-old woman with high-grade glioma in the right frontal lobe who was admitted to the surgical theater for craniotomy and excision of the tumor. During the general anesthesia procedure and just before inserting the central venous line, her end-tidal CO2 and O2 saturation dropped sharply. The anesthesiologist quickly responded with an aggressive resuscitation procedure that included aspiration through the central venous line, 100% O2, and IV administration of ephedrine 6 mg, colloid 500 mL, normal saline 500 mL, and heparin 5000 IU. The patient was extubated and remained in the supine position until she regained consciousness and her vital signs returned to normal. Subsequent radiological examination revealed a massive bilateral PE. A retrievable inferior vena cava (IVC) filter was inserted, and enoxaparin anticoagulant therapy was prescribed to stabilize the patient's condition. After 3 weeks, she underwent an uneventful craniotomy procedure and was discharged a week later under the enoxaparin therapy. CONCLUSIONS The successful management of intraoperative PE requires a quick, accurate diagnosis accompanied with an aggressive, fast response. Anesthesiologists are usually the ones who are held accountable for the diagnosis and early management of this complication. They must be aware of the possibility of such a complication and be ready to react properly and decisively in the operation theater.


HIV-1 vaccine design through minimizing envelope metastability.
Overcoming envelope metastability is crucial to trimer-based HIV-1 vaccine design. Here, we present a coherent vaccine strategy by minimizing metastability. For 10 strains across five clades, we demonstrate that the gp41 ectodomain (gp41ECTO) is the main source of envelope metastability by replacing wild-type gp41ECTO with BG505 gp41ECTO of the uncleaved prefusion-optimized (UFO) design. These gp41ECTO-swapped trimers can be produced in CHO cells with high yield and high purity. The crystal structure of a gp41ECTO-swapped trimer elucidates how a neutralization-resistant tier 3 virus evades antibody recognition of the V2 apex. UFO trimers of transmitted/founder viruses and UFO trimers containing a consensus-based ancestral gp41ECTO suggest an evolutionary root of metastability. The gp41ECTO-stabilized trimers can be readily displayed on 24- and 60-meric nanoparticles, with incorporation of additional T cell help illustrated for a hyperstable 60-mer, I3-01. In mice and rabbits, these gp140 nanoparticles induced tier 2 neutralizing antibody responses more effectively than soluble trimers.


Focal adhesion kinase enhances signaling through the Shc/extracellular signal-regulated kinase pathway in anaplastic astrocytoma tumor biopsy samples.
Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that on activation generates signals that can modulate crucial cell functions, including cell proliferation, migration, and survival. In vitro, overexpression of FAK has been shown to promote cell proliferation by signaling through the Ras/mitogen-activated protein kinase cascade in several cell types. We have shown previously that overexpression of exogenous FAK lacking alternative splicing in malignant astrocytoma clones injected intracerebrally into SCID mouse brains promotes tumor cell proliferation. Here, we show that in anaplastic astrocytoma biopsy samples, FAK is expressed as an unspliced variant and migrates with a faster mobility similar to that observed in embryonic brain. Compared with nonneoplastic adult brain biopsies, the levels of FAK protein are elevated as are its levels of activation as assessed by autophosphorylation and overall tyrosine phosphorylation. The activity of Src kinase in these tumors is also elevated, as well as the activity of Src kinase associated with FAK; the latter may result in enhanced Src kinase phosphorylation of FAK. Phosphorylated Shc is associated with FAK in the anaplastic astrocytoma biopsy samples and in astrocytoma cells overexpressing FAK in vitro but not in nonneoplastic brain biopsy samples. Elevated extracellular signal-regulated kinase-2 activation and elevated expression of cyclins D and E are also found in anaplastic astrocytoma biopsy samples. These data provide evidence that the increased FAK activity in these tumors contributes to phosphorylation of Shc and likely to the promotion of Ras activity, extracellular signal-regulated kinase-2 activation, and cell proliferation in vivo.


Nonspecific uptake and homeostasis drive the oceanic cadmium cycle.
The global marine distributions of Cd and phosphate are closely correlated, which has led to Cd being considered as a marine micronutrient, despite its toxicity to life. The explanation for this nutrient-like behavior is unknown because there is only one identified biochemical function for Cd, an unusual Cd/Zn carbonic anhydrase. Recent developments in Cd isotope mass spectrometry have revealed that Cd uptake by phytoplankton causes isotopic fractionation in the open ocean and in culture. Here we investigate the physiochemical pathways that fractionate Cd isotopes by performing subcellular Cd isotope analysis on genetically modified microorganisms. We find that expression of the Cd/Zn carbonic anhydrase makes no difference to the Cd isotope composition of whole cells. Instead, a large proportion of the Cd is partitioned into cell membranes with a similar direction and magnitude of Cd isotopic fractionation to that seen in surface seawater. This observation is well explained if Cd is mistakenly imported with other divalent metals and subsequently managed by binding within the cell to avoid toxicity. This process may apply to other divalent metals, whereby nonspecific uptake and subsequent homeostasis may contribute to elemental and isotopic distributions in seawater, even for elements commonly considered as micronutrients.


[Subsequent pregnancy among adolescents].
To evaluate epidemiological aspects in recurrent adolescence pregnancy. Cohort study including 187 pregnant adolescents attended and followed-up for five years after delivery in an adolescent's attendance service in Ceará state. Age group, being or not at school, living with parents, schooling, marital status and the present partner's condition were analyzed. Data were processed by the EPI-INFO program. Statistical analysis of the independent variables (age, schooling, being at school, having a job, living with parents, marital status and switching partners) was done and compared to the dependent variable (being or not pregnant after five years). The Fisher's exact test was used to evaluate the association among factors which could influence the pregnancy recurrence, the association being present when p<0.05. Risks related to schooling, marital status and multiple partners have been calculated, since these were significant factors for pregnancy recurrence. 61% of the adolescents got pregnant in the five years after the first delivery. Factors such as age, school, work or living with parents were not protective. Nevertheless, when the adolescents had eight or less years of schooling, the risk of getting pregnant has almost duplicated (relative risk (RR)=1.8 (CI 95%=1.3-2.6)). New pregnancies were more frequent among the single adolescents without a stable partner (RR=1.3 (CI 95%=1.1-1.6) and among the ones who had multiple partners (RR=1.4 (CI 95%=1.1-1.7)). Low schooling, multiple partners and non-stable bonds were risk factors for pregnancy recurrence.


The Italian affair: the employment of parallel-plate ionization chambers for dose measurements in high dose-per-pulse IORT electron beams.
At the high dose-per-pulse rates used by some intraoperative radiotherapy (IORT) units, the employment of ionization chambers for dose measurements needs an appropriate correction (k(sat)) for ion recombination. Through a revision of the existing literature, the authors compared different methods for the determination of the recombination correction factor and their impact on clinical dosimetry. A dosimetric characterization of IORT electron beams from a Linac Hitesys Novac7 (Aprilia-Latina, Italy) was performed. Dose-to-water (D(w)) values were measured with dose-per-pulse independent chemical dosimeters (operated by the Italian Primary Standard Dosimetry Laboratory, ENEA) and compared to doses obtained by two different parallel-plate ionization chamber models (Markus and Advanced Markus, PTW, Freiburg, Germany). For dose measurements using ionization chambers, the authors applied two different methods for the determination of the ion recombination correction factor (k(sat)), as suggested in previous articles. The first method is based on the experimental estimation of the free-electron fraction values p; the second one is based on the "nonstandard" two-voltage analysis including the free-electron component. For a Markus type chamber, there is a good agreement between the results on k(sat) and those reported in the literature for both methods, while for the Advanced Markus chamber, no data are available for comparison. Comparing values of D(w) obtained by dose-per-pulse independent dosimeters and by ionization chambers measurements corrected using the two different approaches, the authors can conclude that the k(sat) factor determination is very critical and that only an experimental protocol using ionization chamber intercalibration can be considered reliable.


Space plasma physics: electron flux intensity distributions observed in response to particle beam emissions.
Modifications of the suprathermal electron population were observed by an electron spectrometer on Spacelab 1 during electron beam injections. The instrument covered its energy range (100 to 12,500 electron volts) and field of view ( approximately 2pi) with high energy, angle, and time resolution. The measurements demonstrate the presence of strong beam-plasma interactions during high-current modes of accelerator operations. Spacecraft charging could be studied as well as processes that accelerated electrons to more than four times the injection energy.


Induction of the heat shock protein ClpB affects cold acclimation in the cyanobacterium Synechococcus sp. strain PCC 7942.
The heat shock protein ClpB is essential for acquired thermotolerance in cyanobacteria and eukaryotes and belongs to a diverse group of polypeptides which function as molecular chaperones. In this study we show that ClpB is also strongly induced during moderate cold stress in the unicellular cyanobacterium Synechococcus sp. strain PCC 7942. A fivefold increase in ClpB (92 kDa) content occurred when cells were acclimated to 25 degrees C over 24 h after being shifted from the optimal growth temperature of 37 degrees C. A corresponding increase occurred for the smaller ClpB' (78 kDa), which arises from a second translational start within the clpB gene of prokaryotes. Shifts to more extreme cold (i.e., 20 and 15 degrees C) progressively decreased the level of ClpB induction, presumably due to retardation of protein synthesis within this relatively cold-sensitive strain. Inactivation of clpB in Synechococcus sp. increased the extent of inhibition of photosynthesis upon the shift to 25 degrees C and markedly reduced the mutant's ability to acclimate to the new temperature regime, with a threefold drop in growth rate. Furthermore, around 30% fewer delta clpB cells survived the shift to 25 degrees C after 24 h compared to the wild type, and more of the mutant cells were also arrested during cell division at 25 degrees C, remaining attached after septum formation. Development of a cold thermotolerance assay based on cell survival clearly demonstrated that wild-type cells could acquire substantial resistance to the nonpermissive temperature of 15 degrees C by being pre-exposed to 25 degrees C. The same level of cold thermotolerance, however, occurred in the delta clpB strain, indicating ClpB induction is not necessary for this form of thermal resistance in Synechococcus spp. Overall, our results demonstrate that the induction of ClpB contributes significantly to the acclimation process of cyanobacteria to permissive low temperatures.


MR imaging of heat stroke: external capsule and thalamic T1 shortening and cerebellar injury.
We present a case of increased signal intensity of the cerebrum (symmetric involvement of the paraventricular thalamus and external capsule) and cerebellum on both T1- and T2-weighted images in a patient with documented heat stroke. An ischemic and hemorrhagic mechanism is proposed, and the contributions of the direct effects of hyperthermia are discussed.


A multivariate predictive modeling approach reveals a novel CSF peptide signature for both Alzheimer's Disease state classification and for predicting future disease progression.
To determine if a multi-analyte cerebrospinal fluid (CSF) peptide signature can be used to differentiate Alzheimer's Disease (AD) and normal aged controls (NL), and to determine if this signature can also predict progression from mild cognitive impairment (MCI) to AD, analysis of CSF samples was done on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. The profiles of 320 peptides from baseline CSF samples of 287 subjects over a 3-6 year period were analyzed. As expected, the peptide most able to differentiate between AD vs. NL was found to be Apolipoprotein E. Other peptides, some of which are not classically associated with AD, such as heart fatty acid binding protein, and the neuronal pentraxin receptor, also differentiated disease states. A sixteen-analyte signature was identified which differentiated AD vs. NL with an area under the receiver operating characteristic curve of 0.89, which was better than any combination of amyloid beta (1-42), tau, and phospho-181 tau. This same signature, when applied to a new and independent data set, also strongly predicted both probability and rate of future progression of MCI subjects to AD, better than traditional markers. These data suggest that multivariate peptide signatures from CSF predict MCI to AD progression, and point to potentially new roles for certain proteins not typically associated with AD.


Assessing anti-T. cruzi candidates in vitro for sterile cidality.
Total clearance of the T. cruzi infection - referred to herein as "sterile cure" - seems to be a critical prerequisite for new drug candidates for Chagas disease, ensuring long-term beneficial effects for patients in the chronic indeterminate stage. This requirement is notably supported by the recent findings of clinical studies involving posaconazole and fosravuconazole, where the majority of patients treated eventually relapsed after an apparent clearance of parasitaemia at the end of treatment. We have adapted an in vitro system to predict the ability of a compound to deliver sterile cure. It relies on mouse peritoneal macrophages as host cells for Trypanosoma cruzi amastigotes. The macrophages do not proliferate, allowing for long-term testing and wash-out experiments. Giemsa staining followed by microscopy provides a highly sensitive and specific tool to quantify the numbers of infected host cells. Combining macrophages as host cells and Giemsa staining as the read-out, we demonstrate that posaconazole and other CYP51 inhibitors are unable to achieve complete clearance of an established T. cruzi infection in vitro in spite of the fact that these compounds are active at significantly lower concentrations than the reference drugs benznidazole and nifurtimox. Indeed, a few macrophages remained infected after 96 h of drug incubation in the presence of CYP51 inhibitors-albeit at a very low parasite load. These residual T. cruzi amastigotes were shown to be viable and infective, as demonstrated by wash-out experiments. We advocate characterizing any new anti-T. cruzi early stage candidates for sterile cidality early in the discovery cascade, as a surrogate for delivery of sterile cure in vivo.


A revised leopard frog phylogeny allows a more detailed examination of adaptive evolution at ranatuerin-2 antimicrobial peptide loci.
Ranatuerins are antimicrobial peptides of the innate immune system found in ranid frogs. We previously presented evidence that a positive selective sweep had fixed a single allele at the Ranatuerin2 locus in the northern leopard frog (Rana pipiens). In this paper, we further investigate the evolutionary history of ranatuerins as follows. First, we sequenced Ranatuerin2 in additional individuals of R. pipiens and related frog species and compared diversity and divergence at these sequences with that at four putatively neutrally evolving loci. Second, we asked whether the evolutionary patterns observed at Ranatuerin2 were typical for ranatuerin loci by sequencing our samples at a paralogous locus, Ranatuerin2b, and performing the same neutrality tests. Ranatuerin2b also showed strong and significant evidence of at least one selective sweep. Third, we used the neutral loci to independently resolve conflicting hypotheses about phylogenetic relationships among our study species. Both the neutral loci and the ranatuerin loci supported an older phylogeny inferred from allozyme data and strongly rejected a more recent phylogeny inferred from mitochondrial DNA. Finally, in order to test whether the sweep was driven by the evolution of substantially new peptide function, we used the phylogeny to reconstruct the hypothetical Ranatuerin2 peptide that existed before the sweep. We synthesized this peptide and tested its activity and that of the extant peptide against six bacterial pathogens of frogs. We observed antibacterial activity but found no significant functional differences between the two peptides.


Emergent chiroptical properties in supramolecular and plasmonic assemblies.
This tutorial provides a comprehensive description of the origin of chiroptical properties of supramolecular and plasmonic assemblies in the UV-visible region of the electromagnetic spectrum. The photophysical concepts essential for understanding chiroptical signatures are presented in the first section. Just as the oscillator strength (a positive quantity) is related to absorption, the rotational strength (either a positive or a negative quantity) defines the emergence of chiroptical signatures in molecular/plasmonic systems. In supramolecular systems, induced circular dichroism (ICD) originates through the off-resonance coupling of transition dipoles in chiral inclusion complexes, while exciton coupled circular dichroism (ECD) originates through the on-resonance exciton coupling of transition dipoles in chiral assemblies resulting in the formation of a bisignated CD signal. In bisignated ECD spectra, the sign of the couplet is determined not only by the handedness of chiral supramolecular assemblies, but also by the sign of the interaction energy between transition dipoles. Plasmonic chirality is briefly addressed in the last section, focusing on inherent chirality, induced chirality, and surface plasmon-coupled circular dichroism (SP-CD). The oscillator strength is of the order of 1 in molecular systems, while it becomes very large (104-105) in plasmonic systems due to the collective plasmonic excitations, resulting in intense CD signals, which can be exploited for the design of plasmonic metamaterial platforms for chiral sensing applications.


Distamycin A selectively inhibits Acanthamoeba RNA synthesis and differentiation.
The effects of distamycin A on Acanthamoeba transcription, growth and differentiation were determined. Distamycin A inhibits transcription both in vitro and in vivo and can displace from DNA the transcription activator TATA binding protein promoter binding factor (TPBF). Inhibition in vivo is surprisingly selective for large rRNA precursors, 5S rRNA, profilin, S-adenosylmethionine synthetase, and extendin. Transcription from the TATA binding protein (TBP), TPBF, protein disulfide isomerase, tubulin and RNA polymerase II large subunit genes is only slightly inhibited. Moreover the rate of 5S rRNA transcription eventually recovers and exceeds that of untreated cells, while profilin transcription remains inhibited. Distamycin A inhibition is accompanied by a complex pattern of alterations to steady state levels of mRNAs. Actin, profilin and S-adenosylmethionine synthetase mRNAs are degraded, whereas mRNA encoding TBP is increased slightly in abundance. Transcription inhibition is accompanied by cessation of growth and severe morphological changes to Acanthamoeba, which are consistent with loss of production of mRNA encoding cytoskeletal proteins. Distamycin A also prevents starvation-induced differentiation of Acanthamoeba, in part due to complete prevention of cellulose production and cell wall formation.


Applicability of the principle of respect for autonomy: the perspective of Turkey.
Turkey has a complex character, which has differences from the Western world or Eastern Asia as well as common points. Even after more than a century of efforts to modernise and integrate with the West, Turkish society has values that are different from those of the West, as well as having Western values. It is worth questioning whether ordinary Turkish people show an individualistic character. The principle of respect for individual autonomy arises from a perception of oneself as an individual, and the person's situation may affect the applicability of the principle. Patients who perceive themselves to be members of a community rather than free persons and who prefer to participate in the common decisions of the community and to consider the common interest and the common value system of the community concerning problems of their life (except healthcare or biomedical research) rather than to decide as independent, rational individuals may not be competent to make an autonomous choice. Expectations that such patients will behave as autonomous individuals may be unjustified. The family, rather than the patient, may take a primary role in decisions. A flexible system considering cultural differences in the concept of autonomy may be more feasible than a system following strict universal norms.


Optogenetic insights on the relationship between anxiety-related behaviors and social deficits.
Many psychiatric illnesses are characterized by deficits in the social domain. For example, there is a high rate of co-morbidity between autism spectrum disorders and anxiety disorders. However, the common neural circuit mechanisms by which social deficits and other psychiatric disease states, such as anxiety, are co-expressed remains unclear. Here, we review optogenetic investigations of neural circuits in animal models of anxiety-related behaviors and social behaviors and discuss the important role of the amygdala in mediating aspects of these behaviors. In particular, we focus on recent evidence that projections from the basolateral amygdala (BLA) to the ventral hippocampus (vHPC) modulate anxiety-related behaviors and also alter social interaction. Understanding how this circuit influences both social behavior and anxiety may provide a mechanistic explanation for the pathogenesis of social anxiety disorder, as well as the prevalence of patients co-diagnosed with autism spectrum disorders and anxiety disorders. Furthermore, elucidating how circuits that modulate social behavior also mediate other complex emotional states will lead to a better understanding of the underlying mechanisms by which social deficits are expressed in psychiatric disease.


Amyoplasia revisited.
Amyoplasia is a specific type and the most common form of arthrogryposis (multiple congenital contractures). It is a clinical diagnosis at this time. Care should be used making the diagnosis because of the implications for recurrence, natural history, associated anomalies, and both etiology and pathogenesis. We reviewed over 600 published reports and 2,500 individual records to identify the 560 individuals reported here. Affected limbs had characteristic positions with fatty-fibrous replacement of muscle. Upper limb involvement was usually characterized by extended elbows. Lower limbs were held in various positions at birth; however, equinovarus positioning of feet was almost always present. Symmetric involvement was common. Among 560 affected individuals, subtypes were identified: four-limb symmetric involvement (331/560 = 55.9%), severe involvement (41/560 = 7.3%), three-limb involvement (27/560 = 4.8%), upper limb only Amyoplasia (ULA; 94/560 = 16.8%), and lower limb only Amyoplasia (LLA; 25/560 = 15.5%). Discordant monozygotic twinning was increased, occurring in 6.6% (37/560; OR 10.9). A variety of additional anomalies were seen, attributed to apparent vascular compromise. Gastrointestinal vascular compromise-type anomalies were present in 9.1% (51/560), trunk muscle defects in another 2.7% (15/560), digit compromise in 12.1% (68/560), constriction rings in 4.3% (24/560), and perinatal long bone fractures in 10.5% (59/560). Although prenatal ultrasound became the standard of care in 1990, only about one quarter of affected pregnancies were diagnosed prenatally since 1990. Amyoplasia appears to be completely sporadic. Novel pathogenetic mechanisms for the congenital anomalies seen in Amyoplasia need to be identified.


Caregiver Medication Management and Understanding After Pediatric Hospital Discharge.
Caregivers frequently make mistakes when following instructions on discharge medications, and these instructions often contain discrepancies. Minimal literature reflects inpatient discharges. Our objective was to describe failures in caregiver management and understanding of inpatient discharge medications and to test the association of documentation discrepancies and sociodemographic factors with medication-related failures after an inpatient hospitalization. This study took place in an urban tertiary care children's hospital that serves a low-income, minority population. English-speaking caregivers of children discharged on an oral prescription medication were surveyed about discharge medication knowledge 48 to 96 hours after discharge. The primary outcome was the proportion of caregivers who failed questions on a 10-item questionnaire (analyzed as individual question responses and as a composite outcome of any discharge medication-related failure). Bivariate tests were used to compare documentation errors, complex dosing, and sociodemographic factors to having any discharge medication-related failure. Of 157 caregivers surveyed, 70% had a discharge medication-related failure, most commonly because of lack of knowledge about side effects (52%), wrong duration (17%), and wrong start time (16%). Additionally, 80% of discharge instructions provided to caregivers lacked integral medication information, such as duration or when the next dose after discharge was due. Twenty five percent of prescriptions contained numerically complex doses. In bivariate testing, only race and/or ethnicity was significantly associated with having any failure (P = .03). The majority of caregivers had a medication-related failure after discharge, and most discharge instructions lacked key medication information. Future work to optimize the discharge process to support caregiver management and understanding of medications is needed.


Korean Developmental Screening Test for Infants and Children (K-DST): development, applications, and implications for future early childhood development interventions.
Evidence of the importance of early childhood development (ECD) has transformed child health monitoring and screening tools. Development of the Korean Developmental Screening Test for Infants and Children (K-DST) has expanded the applications of child health screening to a large number of infants and children in Korea and is contributing to the early detection of neurodevelopmental disorders and delivery of timely interventions. The previous screening tool (Korean Ages and Stages Questionnaire) raised some concerns, as its lack of consideration of the cultural background of the Korean population can lead to inaccurate or imprecise diagnoses. The K-DST, a tailored tool for Korean infants and children, is a simple and cost-efficient solution for child health monitoring and screening. This review focuses on the development and role of the K-DST in ensuring ECD. Here we review use of the K-DST for ECD screenings and discuss the best strategy for its use in other countries.


A qualitative evaluation of an exercise practitioner in an outpatient child and adolescent mental health service.
Physical activity interventions can confer a range of physical and mental health benefits among young people with mental disorders. In some contexts, such as Ireland, integrated physical activity is not easily available within child and adolescent mental health services. Therefore, an interagency pilot intervention was established in a child and adolescent mental health service in Ireland with the integration of a novel exercise practitioner into the multidisciplinary mental health team. A qualitative evaluation was conducted to understand the impact of the pilot intervention and to understand issues of implementation that arose throughout. In-depth qualitative interviews with service users' parents/guardians (N = 3) and a single focus group with existing service providers (N = 3), framed by the RE-AIM framework were conducted to evaluate the pilot intervention. Data were analysed using thematic analysis to explore themes. Three overarching themes were identified. These were as follows: (i) Making changes toward healthier physical activity behaviours; (ii) An intervention of therapeutic holism; and (iii) The integrated service delivery. This research provides insight on the value of a novel integrated exercise practitioner in outpatient young persons' mental health services in Ireland, indicating an enhanced and complimentary therapeutic service. These findings will be helpful for integrating Exercise Practitioners in this setting going forward.


A Cell-Penetrating Scorpion Toxin Enables Mode-Specific Modulation of TRPA1 and Pain.
TRPA1 is a chemosensory ion channel that functions as a sentinel for structurally diverse electrophilic irritants. Channel activation occurs through an unusual mechanism involving covalent modification of cysteine residues clustered within an amino-terminal cytoplasmic domain. Here, we describe a peptidergic scorpion toxin (WaTx) that activates TRPA1 by penetrating the plasma membrane to access the same intracellular site modified by reactive electrophiles. WaTx stabilizes TRPA1 in a biophysically distinct active state characterized by prolonged channel openings and low Ca2+ permeability. Consequently, WaTx elicits acute pain and pain hypersensitivity but fails to trigger efferent release of neuropeptides and neurogenic inflammation typically produced by noxious electrophiles. These findings provide a striking example of convergent evolution whereby chemically disparate animal- and plant-derived irritants target the same key allosteric regulatory site to differentially modulate channel activity. WaTx is a unique pharmacological probe for dissecting TRPA1 function and its contribution to acute and persistent pain.


The effects of morphology and temperature on the tensile characteristics of carbon nitride nanothreads.
Very recently synthesized carbon nitride nanothreads (CNNTs) by compressing crystalline pyridine show outperform diamond nanothreads in chemical and physical properties. Here, using first-principles-based ReaxFF molecular dynamics (MD) simulations, a comprehensive investigation on the mechanical characteristics of seven experimentally synthesized CNNTs has been performed. All CNNTs exhibit unique tensile properties that change with molecular morphology, atomic arrangement and the distribution of nitrogen in the skeleton. The CNNTs with more effective covalent bonds at cross-sections are more mechanically robust. Surprisingly, a tiny CNNT with periodic unit structures of 5462-cage shows extreme ductility because of the formation of a linear polymer via 4-step dissociation-and-reformation of bonds at extremely low temperatures in the range of 1-15 K; however, it shows brittle failure at one cross-section with low ductility at higher temperatures similar to other CNNTs at different temperatures; this offers a feasible way to design a kind of lightweight material that can be used in ultra-low temperature conditions, for example, the harsh deep space environment. The results also show that temperature significantly affects the fracture stress and rupture strain but not the effective stiffness. The analysis of atomic bond orders and bond lengthening reveals that the unique nonlinear elasticity of CNNTs is attributed to the occurrence of local bond transformations. This study provides physical insights into the tensile characteristics of CNNTs for the design and application of CNNT-based nanostructures as multifunctional materials.


Phorbol ester receptors and protein kinase C in primary neuronal cultures: development and stimulation of endogenous phosphorylation.
Embryonic rat neurons cultured in defined medium, essentially in the absence of glia, were highly enriched in phorbol ester receptors. The neurons displayed a single class of phorbol 12,13-dibutyrate binding sites with a maximum binding capacity, after 10 d in culture, of 18.6 pmol/mg protein and an apparent dissociation constant of 7.1 nM. Phorbol ester binding sites were associated with protein kinase C, which represented a major protein kinase activity in primary neuronal cultures. Ca2+-phosphatidylserine-sensitive phosphorylation of endogenous substrates was more marked than that observed in the presence of cyclic AMP or Ca2+ and calmodulin. Phorbol ester receptors and protein kinase C levels were critically dependent on the culture age. Thus, about a 20-fold increase in binding sites occurred during the first week in culture and was accompanied by a corresponding increase in Ca2+-phosphatidylserine-sensitive protein phosphorylation in soluble neuronal extracts. These changes largely paralleled a similar rise in phorbol ester binding during fetal development in vivo. The apparent induction of phorbol ester receptors was specific relative to other cellular proteins and could be inhibited by cycloheximide or Actinomycin D. Phosphorylation of endogenous substrates in intact cultured neurons paralleled the age-dependent increase in protein kinase C. Furthermore, 32P incorporation into several major phosphoproteins was markedly augmented by treating the neuronal cultures with phorbol esters. Such phosphorylation events may provide a clue to the significance of protein kinase C in developing neurons.


Basic aminopeptidase from rabbit kidney: purification and partial characterization.
The aminopeptidase activity of a homogenate of rabbit kidney treated with Triton X-100 was measured using L-aminoacyl-2-naphthylamides (AA-NA). After gradient elution ion-exchange chromatography, four peaks of aminopeptidase activity were eluted. The enzyme eluted at 450 microS containing 33.5% of the activity towards Arg-NA was applied to a Superdex 75 column and presented only one protein band on 10% SDS-polyacrylamide gel electrophoresis. This enzyme has an apparent molecular mass of 78 kDa, is five-fold activated by 0.15 M NaCl and the highest Vmax/KM ratio was obtained with Arg-NA. Enzyme activity was inhibited 100% by 0.13 mM sodium p-hydroxymercuribenzoate, 20% by 0.75 mM EDTA and 100% by 0.66 mM o-phenanthroline. Puromycin and bestatin behaved like competitive inhibitors with a Ki of 0.60 mM and 5.0 microM and 5.0 microM, respectively.


Application of Multiplexed Replica Exchange Molecular Dynamics to the UNRES Force Field: Tests with alpha and alpha+beta Proteins.
The replica exchange (RE) method is increasingly used to improve sampling in molecular dynamics (MD) simulations of biomolecular systems. Recently, we implemented the united-residue UNRES force field for mesoscopic MD. Initial results from UNRES MD simulations show that we are able to simulate folding events that take place in a microsecond or even a millisecond time scale. To speed up the search further, we applied the multiplexing replica exchange molecular dynamics (MREMD) method. The multiplexed variant (MREMD) of the RE method, developed by Rhee and Pande, differs from the original RE method in that several trajectories are run at a given temperature. Each set of trajectories run at a different temperature constitutes a layer. Exchanges are attempted not only within a single layer but also between layers. The code has been parallelized and scales up to 4000 processors. We present a comparison of canonical MD, REMD, and MREMD simulations of protein folding with the UNRES force-field. We demonstrate that the multiplexed procedure increases the power of replica exchange MD considerably and convergence of the thermodynamic quantities is achieved much faster.


PROMOTING MITOCHONDRIAL DYNAMIC EQUILIBRIUM ATTENUATES SEPSIS-INDUCED ACUTE LUNG INJURY BY INHIBITING PROINFLAMMATORY POLARIZATION OF ALVEOLAR MACROPHAGES.
Sepsis-induced acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by widespread pulmonary inflammation and immune response, in which proinflammatory polarization of alveolar macrophages (AMs) plays an important role. Mitochondria are the key intracellular signaling platforms regulating immune cell responses. Moreover, accumulating evidence suggests that the mitochondrial dynamics of macrophages are imbalanced in sepsis and severe ALI/ARDS. However, the functional significance of mitochondrial dynamics of AMs in septic ALI/ARDS remains largely unknown, and whether it regulates the polarized phenotype of AMs is also unclear. Here, we demonstrated that the mitochondrial dynamics of AMs are imbalanced, manifested by impaired mitochondrial fusion, increased fission and mitochondrial cristae remodeling, both in septic models and ARDS patients. However, suppressing excessive mitochondrial fission with Mdivi-1 or promoting mitochondrial fusion with PM1 to maintain mitochondrial dynamic equilibrium in AMs could inhibit the polarization of AMs into proinflammatory phenotype and attenuate sepsis-induced ALI. These data suggest that mitochondrial dynamic imbalance mediates altered polarization of AMs and exacerbates sepsis-induced ALI. This study provides new insights into the underlying mechanisms of sepsis-induced ALI, suggesting the possibility of identifying future drug targets from the perspective of mitochondrial dynamics in AMs.


Comparison of crystalloid and sanguineous cardioplegic solutions in the dog.
Myocardial protection provided by 2 types of cold cardioplegic solution and by cold saline solution was compared experimentally in dogs on cardiopulmonary bypass. Techniques and solutions used simulated clinical conditions. Serial biopsies of myocardium were assayed for adenosine triphosphate, adenosine diphosphate, and adenosine monophosphate. Maintenance and recovery of each phosphate was calculated as a percentage of the prebypass value for each type of solution; these values were used to compare the myocardial protection afforded by the 3 solutions. A difference in these values was not observed between the 2 types of cardioplegic solution; both values were greater than for the control solution, which may indicate improved myocardial protection with cardioplegic arrest.


Climate change shifts natural selection and the adaptive potential of the perennial forb Boechera stricta in the Rocky Mountains.
Heritable genetic variation is necessary for populations to evolve in response to anthropogenic climate change. However, antagonistic genetic correlations among traits may constrain the rate of adaptation, even if substantial genetic variation exists. We examine potential genetic responses to selection by comparing multivariate genetic variance-covariances of traits and fitness (multivariate Robertson-Price identities) across different environments in a reciprocal transplant experiment of the forb Boechera stricta in the Rocky Mountains. By transplanting populations into four common gardens arrayed along an elevational gradient, and exposing populations to control and snow removal treatments, we simulated future and current climates and snowmelt regimes. Genetic variation in flowering and germination phenology declined in plants moved downslope to warmer, drier sites, suggesting that these traits may have a limited ability to evolve under future climates. Simulated climate change via snow removal altered the strength of selection on flowering traits, but we found little evidence that genetic correlations among traits are likely to affect the rate of adaptation to climate change. Overall, our results suggest that climate change may alter the evolutionary potential of B. stricta, but reduced expression of genetic variation may be a larger impediment to adaptation than constraints imposed by antagonistic genetic correlations.


Targeted siRNA Delivery Using a Lipo-Oligoaminoamide Nanocore with an Influenza Peptide and Transferrin Shell.
Developing RNA-interference-based therapeutic approaches with efficient and targeted cytosolic delivery of small interfering RNA (siRNA) is remaining a critical challenge since two decades. Herein, a multifunctional transferrin receptor (TfR)-targeted siRNA delivery system (Tf&INF7) is designed based on siRNA complexes formed with the cationic lipo-oligoamino amide 454, sequentially surface-modified with polyethylene glycol-linked transferrin (Tf) for receptor targeting and the endosomolytic peptide INF7 for efficient cytosolic release of the siRNA. Effective Tf&INF7 polyplex internalization and target gene silencing are demonstrated for the TfR overexpressing tumor cell lines (K562, D145, and N2a). Treatment with antitumoral EG5 siRNA results in a block of tumor cell growth and triggered apoptosis. Tf-modified polyplexes are far more effective than the corresponding albumin- (Alb) or nonmodified 454 polyplexes. Competition experiments with excess of Tf demonstrate TfR target specificity. As alternative to the ligand Tf, an anti-murine TfR antibody is incorporated into the polyplexes for specific targeting and gene silencing in the murine N2a cell line. In vivo distribution studies not only demonstrate an enhanced tumor residence of siRNA in N2a tumor-bearing mice with the Tf&INF7 as compared to the 454 polyplex group but also a reduced siRNA nanoparticle stability limiting the in vivo performance.


Parkinson's Disease: Potential Actions of Lithium by Targeting the WNT/β-Catenin Pathway, Oxidative Stress, Inflammation and Glutamatergic Pathway.
Parkinson's disease (PD) is one of the major neurodegenerative diseases (ND) which presents a progressive neurodegeneration characterized by loss of dopamine in the substantia nigra pars compacta. It is well known that oxidative stress, inflammation and glutamatergic pathway play key roles in the development of PD. However, therapies remain uncertain and research for new treatment is mandatory. This review focuses on the potential effects of lithium, as a potential therapeutic strategy, on PD and some of the presumed mechanisms by which lithium provides its benefit properties. Lithium medication downregulates GSK-3beta, the main inhibitor of the WNT/β-catenin pathway. The stimulation of the WNT/β-catenin could be associated with the control of oxidative stress, inflammation, and glutamatergic pathway. Future prospective clinical trials could focus on lithium and its different and multiple interactions in PD.


Psychological health in midlife among women who have ever lived with a violent partner or spouse.
This study examines the psychological health correlates of domestic violence in a large random sample of mid-aged Australian women (N = 11,310, age 47 to 52 years). Logistic regressions were used to investigate the associations between domestic violence and depression, anxiety, and psychological wellbeing, after adjusting for demographic variables (marital status, income management, area). Results indicate increased odds of having experienced domestic violence for those who had: ever experienced a diagnosis of depression, anxiety, or an "other" psychiatric disorder; recent symptoms of depression and anxiety; used psychoactive medication for depression or anxiety in the 4 weeks prior to the survey; and who reported current depression. Current psychological well-being had an inverse association with a history of domestic violence: As psychological well-being decreased, the odds of having ever experienced domestic violence increased. The results indicate that a history of domestic violence is associated with decreased psychological well-being in mid-aged Australian women.


[Rubomycin Q1--an anthracycline metabolite from Streptomyces coeruleorubidus 2679, a strain producing rubomycin C].
In the programme of screening of biologically active secondary metabolites produced by Streptomyces coeruleorubidus 2679 a new reddish-violet component (rubomycin Q1) with antibacterial and cytotoxic activity was isolated from the culture fluid of the organism. Some physico-chemical and biological properties of a chromatographically pure rubomycin Q1 were investigated. It was shown with the use of 1H NMR, UV, IR and mass spectrometry that rubomycin Q1 was an anthracycline antibiotic (9,10-anhydro-13-desoxycarminomycin).


Short-term outcomes associated with the use of a new powered circular stapler for rectal reconstructions: a retrospective study comparing it to manual circular staplers using inverse probability of treatment weight analysis.
The most common postoperative complication in malignant rectal surgery is anastomotic leakage (AL). AL after anterior or low anterior resection in rectal tumors is a fatal postoperative complication. Recently, the first automated suture circular stapler, which is expected to reduce the incidence of AL, (J&J). MATERIALS AND METHODS: This study included a total of 248 rectal tumor patients who underwent double stapler technique (DST) anastomotic procedures in the department of gastroenterological surgery /pediatric surgery at Gifu University School of Medicine from January 2017 to December 2021. The experience of a single institution utilizing the The Echelon circular™ stapler (ECP stapler:Manual VS Automatic) in rectal surgery cases was evaluated retrospectively from maintained database. One hundred thirty-nine patients (58.4%) were performed by manual circular stapling, 99 patients (41.6%) by powerd circular stapling. Diverting stoma was performed in 45 cases (32.4%) by manual circular stapling, 42 patients (42.4%) by powerd circular stapling Postoperative complications were occurred clavien-dindo grade II or higher in 57 cases (23.9%) and grade III or higher in 20 cases (8.4%). Anastomotic leakage occurred in 14 patients (5.9%) within all grades. After IPTW, the variables of patient characteristics was SMD ≤ 0.2 (Table.3), and there was a significant difference in anastomotic leakage (Odds Ratio (OR), 0.57; 95% Confidence Interval(CI), 0.34-0.98; p = 0.041). In addition, there was no significant difference in postoperative complications in grade II or higher (OR, 0.88; 95%CI, 0.65-1.19; p = 0.417) and grade III or higher (OR, 0.46; 95%CI, 0.29-0.74; p = 0.001) were significantly remarkable lower in powered circular stapling group. In this IPTW comparison of patients undergoing rectal reconstructions, the ECP trial cohort had lower risks of several surgical complications AL and statistically signifcant lower rates of ileus/bowel obstruction, infection, and bleeding as Clavien-Dindo ≥ grade II and III as compared with for whom manual circular staplers were used.


Open Dialogue: A case study on the influence of sharing or withholding reflections during a network meeting.
In Open Dialogue, sharing of reflections by professionals constitutes an important contribution to promoting a polyphonic dialogue between participants. In the inner dialogue, past and future influence the present moment. In this study, we explore the influence of sharing or withholding reflections by professionals on the interplay between inner and outer dialogue. A case study was used with a multi-perspective methodology, which combined video recordings of a network meeting and interviews by using video-stimulated recall with the clients separately, and social workers together afterward. We found that the sharing of reflections by professionals stimulates the inner dialogue and creates an opening for sharing these in the outer dialogue. In addition, we observed that when reflections are withheld, the client's inner dialogue still continues, but their inner dialogue was not shared in the outer dialogue.


Eczema phenotypes and risk of allergic and respiratory conditions in school age children.
Eczema phenotypes based on eczema onset and persistence might better identify groups prone to allergic and respiratory conditions than a binary definition of eczema. We examined the associations of childhood eczema phenotypes with allergic sensitization, allergy, asthma and lung function at school age. This study among 4277 children was embedded in a multi-ethnic population-based prospective cohort study. Five eczema phenotypes (never, early transient, mid-transient, late transient, persistent) based on parental-reported physician-diagnosed eczema from age 6 months until 10 years were identified. At age 10 years, allergic sensitization was measured by skin prick tests, physician-diagnosed allergy and asthma by parent-reported questionnaires, and lung function by spirometry. Adjusted linear, logistic and multinomial regression models were applied. Compared with never eczema, all eczema phenotypes were associated with increased risks of asthma (odds ratios (OR) range (95% confidence interval): 2.68 (1.58, 4.57) to 11.53 (6.65, 20.01)), food and inhalant allergic sensitization (1.72 (1.25, 2.36) to 12.64 (7.20, 22.18)), and physician-diagnosed inhalant allergy (1.92 (1.34, 2.74) to 11.91 (7.52, 18.86)). Strongest effect estimates were observed of early and persistent eczema with the risk of physician-diagnosed food allergy (OR 6.95 (3.76, 12.84) and 35.05 (18.33, 70.00), respectively) and combined asthma and physician-diagnosed allergy (7.11 (4.33, 11.67) and 29.03 (15.27, 55.22), respectively). Eczema phenotypes were not associated with lung function measures. Eczema phenotypes were differentially associated with risks of respiratory and allergic conditions in school-aged children. Children with early transient and persistent eczema might benefit from more intense follow-up for early identification and treatment of asthma and allergies.


Identification of mutations in rat CD59 that increase the complement regulatory activity.
Formation of the membrane attack complex (MAC) of complement on host cells is inhibited by the glycosylphosphatidylinositol- (GPI-) anchored glycoprotein CD59. Published data on the active site of human CD59 are confusing. To clarify these data, we set out to elucidate the active site of a nonprimate CD59 molecule by site-directed mutagenesis. We also undertook to investigate a region of potential species selectivity, and to this end rat CD59 was chosen for all mutations. Our investigations confirmed the proposal that the active site of CD59 is the major hydrophobic groove, with mutations Y36A, W40A, and L54A ablating complement inhibitory function of CD59. Other mutations reducing the function of rat CD59 were I56E, D24A, and D24R. Importantly, mutations at one residue increased the function of rat CD59. The K48E mutation significantly increased function against human rat or rabbit serum, whereas the K48A mutation increased function against human serum alone. A similar mutation in human CD59 (N48E) had no effect on activity against human or rat serum but completely abolished all activity against rabbit serum. These findings suggest that the alpha-helix of human CD59, adjacent to the hydrophobic groove, influences the interaction between human CD59 and rabbit C8, C9, or both.


Acute Appendicitis: A Meta-Analysis of the Diagnostic Accuracy of US, CT, and MRI as Second-Line Imaging Tests after an Initial US.
Purpose To evaluate the sensitivity, specificity, and diagnostic odds ratios of US, CT, and MRI as second-line imaging modalities after initial US for assessing acute appendicitis in children and adults. Materials and Methods A literature search was conducted in Medline and Embase to identify articles that used surgery or histopathologic examination alone or in combination with clinical follow-up or chart review to evaluate the diagnostic accuracy of second-line imaging modalities. The quality of articles was assessed by using the Quality Assessment of Diagnostic Accuracy Studies-2 and the Standards for Reporting of Diagnostic Accuracy tools. Results For studies of children, the number of studies and patients were as follows: US, six studies and 548 patients; CT, nine studies and 1498 patients; MRI, five studies and 287 patients. For studies of adults, the number of studies and patients were as follows: US, three studies and 169 patients; CT, 11 studies and 1027 patients; MRI, six studies and 427 patients. Pooled sensitivities and specificities of second-line US for diagnosis of appendicitis in children were 91.3% (95% confidence interval [CI]: 83.8%, 95.5%) and 95.2% (95% CI: 91.8%, 97.3%), respectively; and in adults, the pooled sensitivities and specificities were 83.1% (95% CI: 70.3%, 91.1%) and 90.9% (95% CI: 59.3%, 98.6%), respectively. Regarding second-line CT in children, the pooled sensitivities and specificities were 96.2% (95% CI: 93.2%, 97.8%) and 94.6% (95% CI: 92.8%, 95.9%); and in adults, the pooled sensitivities and specificities were 89.9% (95% CI: 85.4%, 93.2%) and 93.6% (95% CI: 91.2%, 95.3%), respectively. Regarding second-line MRI in children, pooled sensitivities and specificities were 97.4% (95% CI: 85.8%, 100%) and 97.1% (95% CI: 92.1%, 99.0%); and in adults, the pooled sensitivities and specificities were 89.9% (95% CI: 84.8%, 93.5%) and 93.6% (95% CI: 90.9%, 95.5%), respectively. Conclusion Second-line US, CT, and MRI have comparable and high accuracy in helping to diagnose appendicitis in children and adults, including pregnant women. All three modalities may be valid as second-line imaging in a clinical imaging pathway for diagnosis and management of appendicitis.