Pandemic influenza preparedness in Maryland: improving readiness through a tabletop exercise.
In February 1999, the Maryland Department of Health and Mental Hygiene initiated pandemic influenza planning for the state of Maryland. This process involved several major steps, including the development of the Maryland Pandemic Influenza Preparedness Plan, and culminated in a high-level tabletop exercise to test the plan in April 2004. During the tabletop exercise, participants were presented with nine different fictitious scripts encompassing a single scenario. They were asked to respond to the information presented in each script, discuss organization-specific questions posed by the exercise facilitator, and make decisions regarding action steps that their organization would take in response to the various issues raised. The exercise identified a number of important gaps that need to be addressed, including (1) additional surge capacity specific to a pandemic, (2) greater understanding of the realities and implications of pandemic influenza among elected officials and decision-makers, (3) coordination of pandemic influenza planning with the existing emergency response infrastructure coupled with additional training in incident command, (4) further steps to operationalize several aspects of the Maryland Pandemic Influenza Preparedness Plan, and (5) additional federal guidance.


Socio-cultural and economic barriers, and facilitators influencing men's involvement in antenatal care including HIV testing: a qualitative study from urban Blantyre, Malawi.
Male partner involvement in antenatal care (ANC) is associated with positive maternal and neonatal outcomes. However, only a handful of men attend ANC with their partners. This study aimed to understand the underlying barriers and facilitators influencing men's ANC attendance including HIV testing in Blantyre, Malawi. Data were collected during a formative qualitative study of a cluster-randomised trial. Six focus group discussions (FGDs) with 42 men and women and 20 in-depth interviews (IDIs) were conducted at three primary health centres in urban Blantyre, Malawi. FGD participants were purposively sampled with IDI participants subsequently sampled after FGD participation. Thematic analysis was used to analyse the data. The economic requirement to provide for their families exerted pressure on men and often negatively affected their decision to attend ANC together with their pregnant partners despite obvious benefits. Peer pressure and the fear to be seen by peers queueing for services at ANC, an environment traditionally viewed as a space for women and children made men feel treated as trespassers and with some level of hostility rendering them feeling emasculated when they attend ANC. Health system problems associated with overall organization of the ANC services, which favours women created resistance among men to be involved. An association between ANC and HIV testing services discouraged men from attending ANC because of their fear of testing HIV-positive in the presence of their partners. The availability of a male friendly clinic offering a private, quick, supportive/sensitive and flexible service was considered to be an important incentive that would facilitate men's ANC attendance. Men described compensation to cover transport and opportunity cost for attending the clinic as a motivator to attending ANC services and accepting an HIV test. Peer and economic influences were the most influential barriers of men attending ANC and testing for HIV with their pregnant partners. Addressing these socio-economic barriers and having a male friendly clinic are promising interventions to promote male ANC attendance in this setting.


[Afferent nerve connection among "Hegu" (LI4), "Neiguan" (PC6), "Futu" (LI18) and thyroid gland region: fluorescent double labelling method].
To observe the peripheral and central neural connection of acupoint "Hegu" (LI4), "Neiguan" (PC6), "Futu" (LI18) and the thyroid gland (TG) region with fluorescence double-labelling method. Thirty male Wistar rats were divided into LI4-LI18 group, PC6-LI18 group, TG-LI 18 group, LI 4-TG group, and PC 6-TG group, with 6 rats in each. Fluorescence dyes Propidium Iodide (PI, 10 microL) and Bisbenzimide (Bb, 10 microL) were, separately, injected into those acupoints mentioned above and the TG region. Sixty hours after PI-injection and 12 hours after Bb-injection, the rats under deep anesthesia were transcardiacally perfused with PBS containing 4% polyoxymethylene, followed by taking the spinal cord and dorsal root ganglia (DRGs) of the cervical segments (C1-C8) and thoracic 1 (T1) segment. Fluorescent single- and dual-labeled cells of the sliced DRGs and cervical spinal cord were observed by fluorescence microscope. (1) All PI- and Bb-labeled cells were found to distribute in DRGs from C1-T1 segments. PI single-labeled cells from LI4 and PC6 mainly distributed in DRGs from C4 to C8. Bb single-labeled cells from LI18 and TG region distributed in DRGs from C1-C6. (2) Dual-labeled cells in the LI 4-LI 188 group, PC6-LI18 group, LI4-TG group, and PC6-TG group distributed in DRGs from C3 to C7, suggesting bifurcate peripheral processes of the cervical DRG neurons to innervate LI8, LI4, PC6 and the TG region. And the dual-labeled cells of the TG-LI 18 group distributed mainly in DRGs from C1 to C4. (3) A small number of single-labeled neurons(about 8% of total labeled cells in DRGs) and only several dual-labeled neurons were found in the anterior horn of the cervical spinal cord. LI18, LI4 and PC6 and the thyroid gland have the same peripheral cells in DRGs of C3-C7 segments, suggesting that the bifurcate peripheral innervation may provide an anatomic evidence for the analgesic effect of acupuncture of LI18, LI4 and PC6 on thyroidectomy.


[Georg Friedrich Nicolai: war physician against war].
Georg Friedrich Nicolai was a German professor and heart specialist who was one of the few who protested against the war at the beginning of World War I. As a result, he lost his job and was convicted. After the war, right-wing nationalist students and lack of support from his university superiors made it impossible for him to teach. He left Germany in 1922, never to return. In his book, Die Biologie des Krieges (The Biology of War), which was published in neutral Switzerland in 1917, he contradicted the social Darwinist idea - supported by many physicians as well - that war strengthened humanity, people and races, physically and mentally. On the contrary, he argued, war is biologically counterproductive.


Pirh2 modulates amyloid-β aggregation through the regulation of glucose-regulated protein 78 and chaperone-mediated signaling.
Amyloid-β (Aβ) protein aggregation in the brain is a pathological hallmark of Alzheimer's disease (AD) however, the underlying molecular mechanisms regulating amyloid aggregation are not well understood. Here, we studied the propitious role of E3 ubiquitin ligase Pirh2 in Aβ protein aggregation in view of its regulatory ligase activity in the ubiquitin-proteasome system employing both cellular and sporadic rodent models of AD. Pirh2 protein abundance was significantly increased during Streptozotocin (STZ) induced AD conditions, and transient silencing of Pirh2 significantly inhibited the Aβ aggregation and modified the dendrite morphology along with the substantial decrease in choline level in the differentiated neurons. MALDI-TOF/TOF, coimmunoprecipitation, and UbcH7-linked in vitro ubiquitylation analysis confirmed the high interaction of Pirh2 with chaperone GRP78. Furthermore, Pirh2 silencing inhibits the STZ induced altered level of endoplasmic reticulum stress and intracellular Ca2+ levels in neuronal N2a cells. Pirh2 silencing also inhibited the AD conditions related to the altered protein abundance of HSP90 and its co-chaperones which may collectively involve in the reduced burden of amyloid aggregates in neuronal cells. Pirh2 silencing further stabilized the nuclear translocation of phospho-Nrf2 and inhibited the altered level of autophagy factors. Taken together, our data indicated that Pirh2 is critically involved in STZ induced AD pathogenesis through its interaction with ER-chaperone GRP78, improves the neuronal connectivity, affects the altered level of chaperones, co-chaperones, & autophagic markers, and collectively inhibits the Aβ aggregation.


Morphology of typanosomes from white-tailed deer and wapiti in Michigan.
Trypanosomes were isolated from a wapiti (Cervus canadensis) and 72 white-tailed deer (Odocoileus virginianus) from several locations in Michigan. Although significantly fewer fawns were infected, there were no significant differences in rate of infection between sexes or among geographic areas. From appearance of the trypomastigote, the trypanosome from white-tailed deer belongs in the genus Trypanosoma and the subgenus Megatrypanum. It was morphometrically similar to the common trypanosome of cattle, Trypanosoma theileri.


The association of telomere length and cancer: a meta-analysis.
Telomeres shorten with each cell division and are essential for chromosomal stability. Short telomeres in surrogate tissues (e.g., blood cells) are associated with increased cancer risk in several case-control studies, but findings are inconsistent in prospective studies. We systematically reviewed studies published prior to August 30, 2010, on the association between telomere length (TL) in surrogate tissues and cancer. There were 27 reports on 13 cancers and/or incident cancer investigating this association. The majority, 16, were retrospective case--control studies, 11 were prospective studies. Meta-analyses were conducted to determine ORs and 95% CIs for these studies. Studies on bladder, esophageal, gastric, head and neck, ovarian, renal, and overall incident cancer found associations between short telomeres and these cancers. Non-Hodgkin lymphoma, breast, lung, and colorectal cancer reports were inconsistent. Single studies on endometrial, prostate, and skin cancers were null. In a random-effects meta-analysis, short TL was significantly associated with cancer in retrospective studies (pooled OR for the shortest TL quartile compared with the longest: 2.9, 95% CI: 1.75-4.8, P < 0.0001). The pooled OR for prospective studies was 1.16 (95% CI: 0.87-1.54, P = 0.32). All studies combined yielded a pooled OR of 1.96 (95% CI: 1.37-2.81, P = 0.0001) for the association of short TL and cancer. There is suggestive evidence that short surrogate tissue TL is associated with cancer; the strongest evidence exists for bladder, esophageal, gastric, and renal cancers. Additional prospective studies with consistent methodology are needed to confirm this hypothesis.


Importance of Parameter Settings on the Benefits of Robot-to-Robot Learning in Evolutionary Robotics.
Robot-to-robot learning, a specific case of social learning in robotics, enables multiple robots to share learned skills while completing a task. The literature offers various statements of its benefits. Robots using this type of social learning can reach a higher performance, an increased learning speed, or both, compared to robots using individual learning only. No general explanation has been advanced for the difference in observations, which make the results highly dependent on the particular system and parameter setting. In this paper, we perform a detailed analysis into the effects of robot-to-robot learning. As a result, we show that this type of social learning can reduce the sensitivity of the learning process to the choice of parameters in two ways. First, robot-to-robot learning can reduce the number of bad performing individuals in the population. Second, robot-to-robot learning can increase the chance of having a successful run, where success is defined as the presence of a high performing individual. Additionally, we show that robot-to-robot learning results in an increased learning speed for almost all parameter settings. Our results indicate that robot-to-robot learning is a powerful mechanism which leads to benefits in both performance and learning speed.


Asymptotic analysis of noise sensitivity in a neuronal burster.
A combination of asymptotic approaches provides a new analysis of the effect of small noise on the bursting cycle of a neuronal burster of elliptic type (type III). The analysis is applied to a stochastic model of an excitable spine, with an activity-dependent stem conductance, that exhibits conditional burst dynamics. First, we give an asymptotic approximation to the probability density for the state of the system. This density is used to compute several quantities which describe the influence of the noise on the transition from the silent to the active phase. Second, we also use a multiscale method to provide a reduced system for analysing the effect of noise on the transition out of the active phase. The combination of these two approaches results in a new framework for a quantitative description of how noise shortens the burst cycle, which measures the significant influence of small noise. For the stochastic spine model, this study suggests that small amplitude noise can significantly influence the activity-dependent morphological plasticity of dendritic spines. The techniques used in this paper combine probabilistic and asymptotic methods, and have been generalized for other noisy nonlinear systems.


[Preeclampsia not (yet) predictable from the blood platelet count].
Platelet activation plays an important role in the pathogenesis of pre-eclampsia as demonstrated by reduced platelet count, increased mean platelet volume and elevated plasma concentrations of beta-thromboglobulin and platelet factor 4 in pre-eclamptic patients. Thrombocytopenia precedes the onset of clinical symptoms of pre-eclampsia. Possibly an enhanced activation state of the platelets in the circulation is present some time before the onset of pre-eclampsia: platelet activation might then be used to predict pre-eclampsia. Flow cytometry is considered the most sensitive technique at this moment to measure the activation of platelets. Fluorescent-labelled antibodies are used to detect antigens that appear on the platelet surface or change their conformation upon activation. During the first and second trimester of pregnancy pre-eclamptic patients have an increased expression of some antigens on the surface of their platelets, such as CD63. There is no reliable platelet test yet to predict the onset of pre-eclampsia.


Preoperative cardiac management of the patient for non-cardiac surgery: an individualized and evidence-based approach.
Preoperative cardiovascular management is an essential component of overall perioperative cardiovascular care. It involves preoperative detection and management of cardiovascular disease and prediction of both short- and long-term cardiovascular risk. It thereby not only affects anaesthetic perioperative management (e.g. choice of anaesthetic drug and method, type of monitoring, and postoperative care) but also surgical decision-making (e.g. postponement, modification, and cancellation of surgical procedure). The ultimate goal of preoperative cardiovascular management is to improve overall patient outcome. This requires individualized management. Although preoperative cardiac management has improved during the past decades, we are not yet in the situation where we can accurately predict individual perioperative risk. The individual stress response and the individual interactions between pharmacological intervention and intra- and postoperative risk factors are highly variable. More importantly, preoperative cardiac management is only one aspect of overall perioperative care. There are numerous intra- and postoperative factors which have been shown to affect overall outcome. However, not all of them can reliably be predicted or modified in a way to positively affect overall outcome. Recognition of such factors and aggressive attempts at appropriate intervention may reduce overall risk more than preoperative management in isolation. Without defining and subsequently targeting intra- and postoperative risk factors, the benefit of preoperative cardiac management will be limited.


Accuracy of cause-of-death coding in Taiwan: types of miscoding and effects on mortality statistics.
The objectives of this study were to assess the accuracy of cause-of-death coding, determine the extent to which coders follow the selection rules of coding set out in the International Classification of Diseases, 9th Revision (ICD-9), and the effects of miscoding on mortality statistics in Taiwan. A systematic sample of 5621 death certificates was reviewed. The underlying cause of death (UCD) selected by the reviewer for each death certificate was compared with that selected by the original coder. The UCD was selected according to ACME (Automated Classification of Medical Entities) Decision Tables. The overall agreement rates between the reviewer and coders according to the three-digit and two-digit categories of ICD-9 were 80.9% and 83.9%, respectively. Good agreement was found for malignant neoplasms (kappa = 0.94) and injuries and poisoning (kappa = 0.97), but there was poor agreement for nephrotic diseases (kappa = 0.74), hypertension-related diseases (kappa = 0.74), and cerebral infarction (kappa = 0.77). Reasons for disagreements included disagreement in nomenclature (42.8%), inappropriate judgement of causal relationships (41.5%), and incorrect interpretation of Selection Rule 3 and Modification Rules (15.7%). This study showed various levels of agreement for different diseases between the reviewer and the original coders in selection of the UCD. Owing to the 'compensatory effect of errors', the national mortality statistics were not affected significantly. The national administration should undertake routine internal studies to control the quality of UCD coding practices.


Diabetes prevalence in populations of South Asian Indian and African origins: a comparison of England and the Netherlands.
We determined whether the overall lower prevalence of type II diabetes in England versus the Netherlands is observed in South-Asian-Indian and African-Caribbean populations. Additionally, we assessed the contribution of health behavior, body size, and socioeconomic position to observed differences between countries. Secondary analyses of population-based standardized individual-level data of 3386 participants were conducted. Indian and African-Caribbean populations had higher prevalence rates of diabetes than whites in both countries. In cross-country comparisons (and similar to whites), Indians residing in England had a lower prevalence of diabetes than those residing in the Netherlands; the prevalence ratio (PR) was 0.35 (95% confidence interval = 0.22 to 0.55) in women and 0.74 (0.50 to 1.10) in men after adjustment for other covariates. Among people of African descent as well, diabetes prevalence was lower in England than in the Netherlands; for women, PR = 0.43 (0.20 to 0.89) and for men, 0.57 (0.21 to 1.49). : The increasing prevalence of diabetes after migration may be modified by the context in which ethnic minority groups live.


Neisseria gonorrhoeae pilin glycan contributes to CR3 activation during challenge of primary cervical epithelial cells.
Expression of type IV pili by Neisseria gonorrhoeae plays a critical role in mediating adherence to human epithelial cells. Gonococcal pilin is modified with an O-linked glycan, which may be present as a di- or monosaccharide because of phase variation of select pilin glycosylation genes. It is accepted that bacterial proteins may be glycosylated; less clear is how the protein glycan may mediate virulence. Using primary, human, cervical epithelial (i.e. pex) cells, we now provide evidence to indicate that the pilin glycan mediates productive cervical infection. In this regard, pilin glycan-deficient mutant gonococci exhibited an early hyper-adhesive phenotype but were attenuated in their ability to invade pex cells. Our data further indicate that the pilin glycan was required for gonococci to bind to the I-domain region of complement receptor 3, which is naturally expressed by pex cells. Comparative, quantitative, infection assays revealed that mutant gonococci lacking the pilin glycan did not bind to the I-domain when it is in a closed, low-affinity conformation and cannot induce an active conformation to complement receptor 3 during pex cell challenge. To our knowledge, these are the first data to directly demonstrate how a protein-associated bacterial glycan may contribute to pathogenesis.


Selected antibodies to leukocyte common antigen (CD45) inhibit human neutrophil chemotaxis.
The CD45 Ag family is a group of high m.w. glycoproteins that are expressed on the plasma membranes of all leukocytes. CD45 has protein tyrosine phosphatase activity and appears to regulate signal transduction and lymphocyte activation by specific association with receptor molecules on T and B lymphocytes. However, little is known about CD45 function in neutrophils (PMN). In this study, PMN were incubated with CD45 mAb and tested for their chemotactic responses to four unrelated chemo-attractants: FMLP, leukotriene B4 (LTB4), recombinant human C5a (C5a), and recombinant human neutrophil-activating protein-1, recently designated IL-8. A panel of CD45 mAb including an IgM mAb, AHN-12.1, and six IgG1 mAb, AHN-12, AHN-12.2, AHN-12.3, AHN-12.4, HLe-1, and KC56(T200), were tested for their effects on PMN chemotaxis. PMN chemotaxis was evaluated with two different membrane assays; one assay quantified the total number of migrating PMN and the other assayed the leading front of migrating PMN. AHN-12.1 and KC56(T200) significantly inhibited PMN chemotaxis to LTB4 and C5a. AHN-12.1 slightly inhibited PMN chemotaxis to FMLP, but KC56(T200) did not. In contrast, AHN-12 and HLe-1 did not significantly inhibit PMN chemotaxis to any of the chemoattractants. None of the CD45 mAb inhibited PMN chemotaxis to neutrophil-activating protein-1/IL-8. None of the CD45 mAb inhibited PMN superoxide production. These results suggest that PMN CD45 epitopes may interact with LTB4 and C5a receptor-associated molecules and regulate chemotactic responses.


[Effects of cultivated Cordyceps sinensis on proliferation and apoptosis of human leukemia K562 cells].
The present study was designed to investigate the effect of cultivated Cordyceps sinensis (CCS) on leukemia-derived K562 cells, and further explore the underlying mechanisms. After routine culture of K562 cells, MTT assay was used to detect the effect of CCS on survivel of human leukemia cell lines K562;DAPI staining was used to observe the morphological changes of the nucleus and AO/EB staining was used to observe cell apoptosis. JC-1 staining was employed to detect the changes in mitochondrial membrane potential. Flow cytometry (FCM) was used to detect cell cycle distribution, and Western blot analysis was used to detect the expression levels of Bax, Bcl-2, caspase 3, caspase 8, cyclin D1, CDK2, and CDK4 in K562 cells. The results showed that CCS (0.345-5.524 g·L⁻¹) substantially suppressed proliferation of K562 cells and induced G₁/S phase arrest in a dose-dependent manner. DAPI and AO/EB staining indicated that cell apoptosis was significantly induced by CCS treatment, accompanied by decreased mitochondrial membrane potential demonstrated by JC-1 staining. Western blot results showed that CCS significantly increased the expression of Bax and, meanwhile, decreased the expression levels of Bcl-2, cyclin D1, CDK2, CDK4, caspase 3 and caspase 8. Collectively, our data demonstrated that CCS dose-dependently suppressed cell proliferation and induced cell apoptosis in K562 cells, and the mechanism might be associated with inducing cell cycle arrest, regulating Bcl-2/Bax ratio and activating the mitochondrial apoptosis pathway.


Constitutive or light-regulated expression of the rolC gene in transgenic potato plants has different effects on yield attributes and tuber carbohydrate composition.
Tetraploid potato clones, transgenic for the rolC gene of Agrobacterium rhizogenes under control of the light-inducible ribulose bisphosphate carboxylase small subunit promoter (rbcS-rolC), were compared, with respect to yield attributes and tuber carbohydrates, with transformed and untransformed controls and with 35S-rolC transgenic potato plants. In rbcS-rolC plants, the expression of the rolC gene was located mainly in leaves, while in 35S-rolC plant transcripts were detected as well in shoots and roots. Phenotypically, rbcS-rolC transgenic plants were found to be slightly reduced in plant size with a few more tillers than control plants. Photosynthetic rate and chlorophyll content were significantly lower in all rolC transgenic plants irrespective of the type of construct used. Tuber yield was not significantly different between controls and rbcS-rolC transgenic plants, but was reduced in the 35S-rolC transformants. Sucrose level was unchanged in all rolC clones investigated, whereas fructose content was significantly enhanced in 35S-rolC transformants, but not in the plants expressing the rolC gene in aerial plant parts only. In both types of rolC transgenic plants, glucose content was lower than in controls, resulting in a significant reduction of reducing sugar in tubers. The results suggest a hormonal influence on the carbohydrate composition of potato tubers.


Improving treatment outcomes for pregnant drug-dependent women using low-magnitude voucher incentives.
The aim of this study was to examine the effectiveness of low-magnitude behavioral incentives in improving attendance for abstinence-treated patients and sustaining illicit-drug abstinence for methadone-treated patients. Subjects were randomly assigned to either incentive or control conditions, with target behaviors differing for the two patient groups (attendance for abstinence-treated and abstinence for methadone-treated patients). Controls received no incentives, whereas incentive subjects could earn $5/day in vouchers during the first 7 days of an intensive outpatient treatment. Results showed that $5/day did not significantly improve attendance in abstinence-treated patients or impact drug abstinence in methadone-treated patients. The data suggest that low-magnitude voucher incentives enhanced treatment attendance by methadone-treated subjects. Although modest monetary incentives had some utility in improving attendance in methadone-treated patients, more potent interventions are needed to improve attendance and maintain abstinence in this high-risk population.


Radiation and resolve: unlocking the synergistic potential of radioimmunotherapy in advanced lung cancer management.
Plain language summary This editorial talks about combining radiation therapy (using high-energy rays to kill cancer cells) and immunotherapy (boosting the body's immune system to fight cancer) to treat advanced lung cancer. When used together, these therapies can work better to kill more cancer cells and help patients live longer. But, there's still a lot we don't know. For instance, we need to figure out the best timing and doses for these treatments, and which patients will benefit the most. The article stresses that more research is needed to answer these questions and make this combined treatment a more effective option for advanced lung cancer patients.


Assessment of interobserver concordance in radiomic tools for lung nodule classification, with a focus on BRODERS and SILA.
While CT lung cancer screening reduces lung cancer-specific mortality, there are remaining challenges. Radiomic tools promiss to address these challenges, however, they are subject to interobserver variability if semi-automated segmentation techniques are used. Herein we report interobserver variability for two validated radiomic tools, BRODERS (Benign versus aggRessive nODule Evaluation using Radiomic Stratification) and CANARY (Computer-Aided Nodule Assessment and Risk Yield). We retrospectively analyzed the CT images of 95 malignant lung nodules of the adenocarcinoma spectrum using BRODERS and CANARY. Cases were identified at Mayo Clinic (n = 45) and Vanderbilt University Medical Center and Nashville/Veteran Administration Tennessee Valley Health Care System (n = 50). Three observers with different training levels (medical student, internal medicine resident and thoracic radiology fellow) each performed lung nodule segmentation. All methods were carried out in accordance with relevant guidelines and regulations. Interclass correlation coefficients (ICC) of 0.77, 0.98 and 0.97 for the average nodule volume, BRODERS cancer probability and Score Indicative of Lesion Aggression (SILA) which summarizes the distribution of the CANARY exemplars indicated good to excellent reliability, respectively. The dice similarity coefficient was 0.79 and 0.81 for the data sets from the two institutions. BRODERS and CANARY are robust radiomics tools with excellent interobserver variability. These tools are simple and reliable regardless the observer/operator's level of training.


Diagnosis and immunotherapy of mould allergy. II. Reproducibility and relationship between skin sensitivity estimated by end-point titration and histamine equivalent reaction using skin prick test and intradermal test.
To determine reproducibility and the optimal way of expressing skin sensitivity, simultaneous skin prick tests (SPT) and intradermal tests (ICT) were performed on 25 mould-allergic patients. The patients had a well-documented history of allergy to Cladosporium and Alternaria and were tested with partially purified standardized extracts of these two mould species. Skin prick tests were carried out on the volar side of the forearm and intradermal tests on the backs of the patients. The skin tests were performed as titration using quadruplicate determinations of 10-fold allergen dilutions. The area of the skin reactions measured by planimetry were plotted in a log-log system as a function of the allergen concentration. The reproducibility (SD/mean area X 100%) of the ICTs was significantly higher than that of the SPTs (17% versus 29%). A very low reproducibility was found with wheal areas less than 5 mm2. The dose response curve of the SPT wheal area was steeper than that obtained with ICT, both concerning ICT wheal and flare. Increasing the allergen concentration with a factor 10 resulted in a doubling of the wheal area in SPT, in contrast to a factor 1.7 using ICT. The coefficient of correlation using linear regression on the dose response curve was always higher than 0.9 with SPT and ICT wheal, but significantly lower with ICT flare. Skin sensitivity was estimated as end-point and histamine equivalent reaction. No significant correlation between SPT and ICT end-point titration was found contrary to the histamine equivalent reaction.(ABSTRACT TRUNCATED AT 250 WORDS)


Modeling of occupant-generated CO2 dynamics in naturally ventilated classrooms.
A numerical method is presented to estimate the concentration of occupant-generated CO(2) for the (time-varying) occupancy typically found in nonforced ventilated elementary school classrooms. Here, the governing mass balance was solved numerically and compared to experimental measurements in order to estimate the respiration and (time-varying) infiltration rates. For the cases studied, we estimate an average CO(2) generation rate per child as 404 mg/min(-1). This is similar to estimates found in the literature for the age and activity level of elementary students, the classroom occupants. The average estimated infiltration rates were found to be larger than those measured from the decay of the tracer gas SF(6) under closed-door static conditions. The in-use infiltration rates were increased by additional air exchange due to people entering and leaving the room. In addition, we show that the difference (or error) between the instantaneous concentration of CO(2) and the time-averaged value recorded by a data-logging CO(2) monitor varies depending on the infiltration rate and sampling time. Therefore, the time interval selected for averaging may increase the overall error of the apparent CO(2) concentration. We conclude that the methods used to measure air exchange rates in naturally ventilated rooms underestimate the actual ventilation rate of a room under "in-use" conditions. However, even with the addition of uncontrolled outdoor air, the concentration of CO(2) in the classrooms studied was higher than recommended to meet air quality objectives.


Antibiotic stewardship: does it work in hospital practice? A review of the evidence base.
Guidelines for developing and implementing stewardship programmes include recommendations on appropriate antibiotic use to guide the stewardship team's choice of potential stewardship objectives. They also include recommendations on behavioural change interventions to guide the team's choice of potential interventions to ensure that professionals actually use antibiotics appropriately in daily practice. To summarize the evidence base of both appropriate antibiotic use recommendations (the 'what') and behavioural change interventions (the 'how') in hospital practice. Published systematic reviews/Medline. The literature shows low-quality evidence of the positive effects of appropriate antibiotic use in hospital patients. The literature shows that any behavioural change intervention might work to ensure that professionals actually perform appropriate antibiotic use recommendations in daily practice. Although effects were overall positive, there were large differences in improvement between studies that tested similar change interventions. The literature showed a clear need for studies that apply appropriate study designs- (randomized) controlled designs-to test the effectiveness of appropriate antibiotic use on achieving meaningful outcomes. Most current studies used designs prone to confounding by indication. In the process of selecting behavioural change interventions that might work best in a chosen setting, much should be learned from behavioural sciences. The challenge for stewardship teams lies in selecting change interventions on the careful assessment of barriers and facilitators, and on a theoretical base while linking determinants to change interventions. Future studies should apply more robust designs and evaluations when assessing behavioural change interventions.


Outcomes research in facial plastic surgery: a review and new directions.
Outcomes research is a fast-growing field of study that focuses on patient-related aspects of medical or surgical outcomes such as satisfaction and quality of life. In the realm of facial plastic surgery, many outcomes are subjective evaluations based on the patient and physician's judgment as to the surgical result, but little has been done to quantify these qualitative results in an objective manner. This paper discusses the basis for outcomes research and suggests its application to the field of facial plastic surgery. Four new facial plastic outcomes instruments have been developed and are provided for the potential use in measuring the quality of life results of rhytidectomy, rhinoplasty, blepharoplasty, and skin rejuvenation procedures.


Hyperemesis and a high water bill.
A male patient aged 28 years was admitted with hyperemesis that did not cease in spite of different therapeutic approaches and had persisted for several days. A wide range of differential diagnoses was excluded and all tests remained without pathological findings. He reported regular cannabis use and showed abnormal bathing behavior taking hot showers several times a day for more than one hour each, which was the only measure to ease his nausea; on the basis of these clinical findings, the diagnosis of cannabinoid hyperemesis syndrome was made. After detoxification, he remained free of symptoms. Cannabinoid hyperemesis syndrome was first described in 2004 in Australia and is an underrecognized cause of hyperemesis and abnormal bathing behavior. To the best of our knowledge, this is the first reported case in Germany.


Completely Free from PAM Limitations: Asymmetric RPA with CRISPR/Cas12a for Nucleic Acid Assays.
Experimentally, Cas12a can recognize multiple protospacer adjacent motif (PAM) sequences and is not restricted to the "TTTN". However, the application of the CRISPR/Cas12a system is still limited by the PAM for double-stranded DNA (dsDNA). Here, we developed asymmetric RPA (Asy-RPA) to completely break the limitations of PAM. Asy-RPA not only achieved efficient amplification but also converted dsDNA to single-stranded DNA (ssDNA) without complicated steps. The ssDNA products activated the trans-cleavage activity of Cas12a, outputting signals. The application of Asy-RPA completely freed Cas12a from the PAM, which can be more widely used in nucleic acid detection, such as lumpy skin disease virus, with an actual detection limit as low as 1.21 × 101 copies·μL-1. More importantly, Cas12a was intolerant to mutations on ssDNA. This provided technical support for the detection and identification of wild-type Mycobacterium tuberculosis (WT-TB) and rifampin-resistant mutant-type M. tuberculosis (MT-TB). The detection limit was as low as 1 fM for 1% mixed samples. The detection and availability of different treatment options for treatment-resistant and WT-TB were significant for the elimination of TB. In summary, the platform consisting of Asy-RPA and CRISPR/Cas12a was suitable for the detection of various viruses and bacteria and was a boon for the detection of dsDNA without recognizable PAM.


Perturbations of Drosophila alpha-actinin cause muscle paralysis, weakness, and atrophy but do not confer obvious nonmuscle phenotypes.
We have investigated accumulation of alpha-actinin, the principal cross-linker of actin filaments, in four Drosophila fliA mutants. A single gene is variably spliced to generate one nonmuscle and two muscle isoforms whose primary sequence differences are confined to a peptide spanning the actin binding domain and first central repeat. In fliA3 the synthesis of an adult muscle-specific isoform is blocked in flight and leg muscles, while in fliA4 the synthesis of nonmuscle and both muscle-specific isoforms is severely reduced. Affected muscles are weak or paralyzed, and, in the case of fliA3, atrophic. Their myofibrils, while structurally irregular, are remarkably normal considering that they are nearly devoid of a major contractile protein. Also surprising is that no obvious nonmuscle cell abnormalities can be discerned despite the fact that both the fliA1- and fliA4-associated mutations perturb the nonmuscle isoform. Our observations suggest that alpha-actinin stabilizes and anchors thin filament arrays, rather than orchestrating their assembly, and further imply that alpha-actinin function is redundant in both muscle and nonmuscle cells.


Comparison of the efficacy of biodegradable and non-biodegradable scintillation liquids on the counting of tritium- and [14C]-labeled compounds.
The widespread use of H and 14C in research has generated a large volume of waste mixed with scintillation liquid, requiring an effective control and appropriate storage of liquid radioactive waste. In the present study, we compared the efficacy of three commercially available scintillation liquids, Optiphase HiSafe 3, Ultima-Gold AB (biodegradable) and Insta-Gel-XF (non-biodegradable), in terms of [14C]-glucose and [ H]-thymidine counting efficiency. We also analyzed the effect of the relative amount of water (1.6 to 50%), radioisotope concentration (0.1 to 100 nCi/ml), pH (2 to 10) and color of the solutions (samples containing 0.1 to 1.0 mg/ml of Trypan blue) on the counting efficiency in the presence of these scintillation liquids. There were few significant differences in the efficiency of 14C and H counting obtained with biodegradable or non-biodegradable scintillation liquids. However, there was an 83 and 94% reduction in the efficiency of 14C and H counting, respectively, in samples colored with 1 mg/ml Trypan blue, but not with 0.1 mg/ml, independent of the scintillation liquid used. Considering the low cost of biodegradable scintillation cocktails and their efficacy, these results show that traditional hazardous scintillation fluids may be replaced with the new safe biodegradable fluids without impairment of H and 14C counting efficiency. The use of biodegradable scintillation cocktails minimizes both human and environmental exposure to hazardous solvents. In addition, some biodegradable scintillation liquids can be 40% less expensive than the traditional hazardous cocktails.


Organ Donation in Turkey: The Knowledge, Approaches and Opinions of Family Physicians.
Considering the gap between organ donors and receivers, it can be assumed that family physicians may play an important role in organ donation. Thus, we aimed to investigate the family physicians' approaches to organ donation in Turkey. In this cross-sectional study, an online survey was sent to all family physicians working in Family Health Centers in Turkey Between Jul - Sep 2018. The survey questioned the knowledge, approaches, and opinions about organ donation issues, besides the socio-demographic characteristics. Most physicians stated that they had given information to their patients on this subject at least occasionally (59.19%, n=998). Among participants, the most common reason for refusing consent for organ donation was the fear of commercial abuse (19.66%, n=244). Most participants (52.61%, n=887) stated that they had been positively affected by the media about organ donation. Some physicians were uncertain about the reliability of the brain death diagnosis (18.39%, n=310). A minor group stated that organ donation might be religiously inappropriate (10.50%, n=177). Although most of the family physicians had a positive manner about organ donation, there was still some wrong knowledge of the participants about legal and medical aspects of organ donation, as well as some other concerns like organ trafficking and reliability of brain death diagnoses, whereas religious concerns were not significant.


Water-soluble nicotinic acetylcholine receptor formed by alpha7 subunit extracellular domains.
Water-soluble models of ligand-gated ion channels would be advantageous for structural studies. We investigated the suitability of three versions of the N-terminal extracellular domain (ECD) of the alpha7 subunit of the nicotinic acetylcholine receptor (AChR) family for this purpose by examining their ligand-binding and assembly properties. Two versions included the first transmembrane domain and were solubilized with detergent after expression in Xenopus oocytes. The third was truncated before the first transmembrane domain and was soluble without detergent. For all three, their equilibrium binding affinities for alpha-bungarotoxin, nicotine, and acetylcholine, combined with their velocity sedimentation profiles, were consistent with the formation of native-like AChRs. These characteristics imply that the alpha7 ECD can form a water-soluble AChR that is a model of the ECD of the full-length alpha7 AChR.


Hepatitis B Virus Reactivation: Risk Factors and Current Management Strategies.
Hepatitis B virus (HBV) is a global disease with significant morbidity and mortality. Worldwide, ~257 million people are chronically infected with HBV, defined as having a positive hepatitis B surface antigen, but millions more have prior HBV exposure indicated by positive hepatitis B core antibody. Reactivation of hepatitis B implies a sudden increase in viral replication in a patient with chronic HBV infection or prior HBV exposure. Hepatitis B virus reactivation (HBVr) can occur spontaneously, but it is more commonly triggered by immunosuppressive therapies for cancer, immunologic diseases, or transplantation. Elimination of hepatitis C virus (HCV) in HBV-HCV coinfected individuals treated with direct-acting antivirals (DAAs) has also been identified as an important cause of HBVr. Hepatitis B virus reactivation is an underappreciated but important complication of common medical therapies that can delay treatment or result in clinical episodes of hepatitis, hepatic failure, or death. In this review, factors associated with HBVr, particularly medication-related risks, are explored. We review data involving rituximab and ofatumumab, doxorubicin, corticosteroids, tumor necrosis factor antagonists, tyrosine kinases, bortezomib, hematologic stem cell transplantation, and DAAs for HCV treatment. In addition, we discuss screening strategies, choice of antiviral prophylaxis, and the optimal duration of therapy for HBVr. With additional awareness, screening, and appropriate antiviral therapy, it is expected that most cases of HBVr can be prevented.


Sources of variance within and among young men in concentrations of 17β-estradiol and testosterone in axillary perspiration.
The most potent estrogen, 17β-estradiol (E2), and its precursor, testosterone (T), play critical roles in mammalian reproductive processes. Evidence indicates that these steroids are present in bioactive form in the excretions of many male mammals. It has been demonstrated that small lipophilic steroids such as E2 can be absorbed by proximate females from male excretions, arriving in the uterus, brain, and other organs where there are estrogen receptors. We took repeated samples of axillary perspiration from men aged 20-30years during vigorous exercise. Both steroids were consistently measurable, with concentrations that ranged from values comparable to those in facial perspiration and urine of both men and women to values that greatly exceeded concentrations observed in any other substrate of men and women. Inter-individual variance in axillary E2 was positively correlated with the extent of intimate experience with women, as assessed by a questionnaire, but unrelated to subjective measures of stress, exercise habits, or phytoestrogen content of diet. In addition, higher levels of axillary E2 were observed in participants when samples were collected by a female (as compared to a male) experimenter. These data are concordant with an hypothesis that male excretion of sex steroids could exert pro-reproductive influences on proximate females.


Current perspective on the cardiovascular effects of coxibs.
Aspirin and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for their anti-inflammatory and analgesic effects. In addition, aspirin is documented to reduce cardiovascular events in selected populations, presumably because of inhibition of platelet aggregation. Yet these drugs are not without toxicity, particularly adverse effects on the gastric mucosa. The gastrointestinal toxicity of nonselective NSAIDs and aspirin derives from the inhibition of the cyclooxygenase (COX) enzyme, COX-1, which synthesizes gastroprotective prostaglandins, while the anti-inflammatory and pain-relieving effects are largely derived from inhibition of COX-2-derived prostaglandins. Available data indicate that the harmful gastric effects of nonselective NSAIDs are reduced by substitution of agents that only inhibit the COX-2 protein. The COX-2-selective inhibitors, however, have also been shown to inhibit the production of vascular prostacyclin, which has vasodilatory effects and inhibits platelet aggregation; unlike nonselective NSAIDs, they do not inhibit the production of thromboxane, an eicosanoid that promotes platelet aggregation. Whether these effects could potentially contribute to a prothrombotic environment is the subject of current, intensive debate. In the Vioxx Gastrointestinal Outcomes Research (VIGOR) trial, there was a higher incidence of cardiovascular thrombotic events in the rofecoxib- vs the naproxen-treated group: 1.67 vs 0.70 per 100 patient years. However, in a pooled analysis of rofecoxib studies, the risk of sustaining a thrombotic cardiovascular event was similar when comparing patients receiving rofecoxib with those receiving placebo, or when comparing patients receiving rofecoxib with those receiving nonnaproxen nonselective NSAIDs. These findings are likely to result, at least in part, from the antiplatelet action of naproxen, which has been shown to be potent and sustained during a typical dosing regimen (500 mg twice daily in VIGOR). In contrast, the other NSAID comparators effect weaker and/or nonsustained antiplatelet action. In the Celecoxib Long-term Arthritis Safety Study (CLASS) trial, there was no difference between celecoxib and the nonselective NSAIDs explored (which did not include naproxen) in cardiovascular event rates. Unlike those in VIGOR, patients in the CLASS trial were allowed to take low-dose aspirin. Thus, despite concerns raised by results of VIGOR, other existing data, including those pooled from existing placebo-controlled trials, do not support a clinically relevant prothrombotic effect of the COX-2 inhibitors. Additional placebo-controlled data, from patients at both high and low risk for cardiovascular events, are warranted to clarify the cardiovascular effects of this class of agents.


Photodynamic therapy of malignant tumors--recent developments.
Photodynamic therapy (PDT) is a promising new cancer treatment modality in which tumor cells are killed as a result of photoactivation of a tumor-localizing photosensitizing agent. Since activating light can be targeted specifically to tumors, and tumor-selective photosensitizing agents are being developed, this treatment has the potential to induce highly selective destruction of malignant cells. To date, PDT has been applied to a large variety of human carcinomas, resulting in successful eradication of single tumor nodules and several types of superficial tumors. Current research is aimed at improving the efficacy and tumor-selectivity and tumor destruction. The most immediate benefits of PDT are likely to be seen in patients treated with a combination of this and other forms of therapy.


Calcium detection in secretion granules of avian oviduct by scanning electron microscopy (SEM) and energy-dispersive X-ray microanalysis (EDX).
Secretion granules in the shell gland, isthmus, and albumin-secreting region of the hen oviduct were analyzed with WET-scanning electron microscopy (SEM) and EDX, a combination of wide-angle backscattered electron detector (BED) and energy-dispersive X-ray microanalyzer (EDX). Glutaraldehyde-fixed but unhydrated, unstained, and uncoated samples were analyzed; Ca was localized in all secretion granules in all three sections of the hen oviduct studied.


Meningococcal Pneumonia in a Young Healthy Male.
A 23-year-old male presented to the emergency department with one-day history of right-sided pleuritic chest pain, haemoptysis, and fever. In the emergency department, the blood pressure was 140/60 mmHg, heart rate 89/min, body temperature 40°C, respiratory rates 20 breaths/min, and oxygen saturation 98% in room air. Physical examination revealed rales and bronchial breathing in the right infrascapular region. Laboratory analysis showed raised white blood cell counts and elevated inflammation markers. Chest X-ray showed right lower lobe consolidation. Intravenous(IV) ceftriaxone and doxycycline were started for the management of community-acquired pneumonia as per the local guideline. Later, on admission, blood culture was positive for Neisseria meningitidis (N. meningitidis). Ceftriaxone was continued for 4 days, and the patient was discharged while being on oral amoxicillin (1 gm TDS) for another 3 days. He remained well during the outpatient follow-up.


Current status and future options for trauma and emergency surgery in Europe.
Currently, there is great variation in the way trauma and non-trauma emergency surgery is organized in Europe. Trauma system development based on orthopedic trauma surgery seems to be more advanced in the central European countries and less developed in Scandinavia, The Baltic States, United Kingdom and the Mediterranean countries. Specific training for trauma surgery correlates with higher level of trauma system development. Multiple common features in the management of a surgical emergency, whether caused by injury or acute disease process, would favor the integration of these two disciplines into a single organizational and educational entity based on regionalization of emergency surgical services and general surgery-based education aiming for multidisciplinary team leadership and decision making skills, and surgical competence in acute life- and limb-saving surgery.


Digital signal processing algorithms for the detection of afferent nerve activity recorded from cuff electrodes.
Due to the very poor signal-to-noise ratios (SNR's) usually encountered with whole nerve-cuff signals, the processing method typically applied, rectification and windowed (bin)-integration (RBI), can have serious shortcomings in extracting reliable information. In order to improve detection accuracy, these signals were further analyzed using statistical signal detection algorithms based on their second and higher order spectra (HOS). A comparison with both analog and digital RBI processing suggests that the statistical methods, due to their ability to separate the signal and noise subspaces, are superior. It was determined that the noise typically encountered with nerve-cuff electrode signals is normally (Gaussian) distributed. Therefore, third-order statistics can be applied to, ideally, completely reject the noise component. When cutaneous nerve recordings from the calcaneal nerve (innervating the heel area) were used in a drop-foot correction neural prosthesis, the detection percentage and the insensitivity to algorithm parameters were increased through the use of these statistical methods as to warrant their real-time implementation, and the inherent additional processing hardware that entails.


The preprotein translocase of the outer mitochondrial membrane: receptors and a general import pore.
Cytosol-synthesized preproteins destined for the mitochondria are transported across the outer membrane by the translocase of the mitochondrial outer membrane (TOM complex). This dynamic transport machinery can be divided into receptors that recognize preprotein targeting signals and components of the general import pore complex that mediate preprotein transport across the outer membrane. This review focuses on recent studies dealing with the central questions regarding the pore-forming subunits, and architecture and gating of the translocation channel of the outer membrane.


The application of advanced computational algorithms used for cooperative communication transmission of vehicular networks: a proposed method.
Telematics will be one of the critical technologies in the future intelligent transportation system and establish communication between vehicles and vehicles, vehicles and networks, and vehicles and people. Thus, vehicles can sense mobile environments and make rational driving decisions. Therefore, the safety and efficiency of traffic flow would be enhanced. However, due to the unknown nature and higher complexity of the connected network environments of vehicles, the utilization of conventional optimization theory fails to generate satisfying results. To address the problem, this article proposes a methodology for collaborative transmission for communication regarding the Internet of Vehicles (IoV) with the help of advanced computational algorithms. The article employs a multi-intelligence advanced computational algorithm to construct a collaborative communication transmission mechanism in the telematics communication system model. The proposed algorithm fully considers the vehicle mobility and quality-of-service (QoS) of telematics services within the network slice. It adjusts the slice's radio resource allocation and parameter settings on an expanded time scale to improve the QoS of telematics services and increase the system's long-term revenue. The simulation results show that the proposed algorithm has a more significant performance improvement than conventional algorithms using telematics information transmission. For example, when the same load conditions are under consideration, the total capacity of the vehicle-to-infrastructure (V2I) link optimized by the proposed algorithm is still higher than that of the other three baseline strategies.


Hepatic intraarterial chemotherapy--current status and future prospects--"If you have a short sword, take a step forward".
The use of hepatic intraarterial (IA) chemotherapy for patients with unresectable liver malignancy has become an increasingly popular mode of therapy. Advances in the understanding of antineoplastic pharmacology, catheter placement technique, and infusion pump design have renewed interest in this approach. Despite inadequacies of the historical data, it appears that IA therapy may be superior to conventional intravenous therapy for patients who have disease limited to the liver, especially from colorectal and hepatocellular malignancies. Unanswered are questions concerning which is the best drug (or drugs) for IA therapy, how to properly integrate IA therapy with surgery and radiation, and how to select patients likely to respond. This renovated technology offers a bright promise for the future of clinical oncology.


Awareness and Determinants of Contraceptive use among Nursing Mothers in Bellary, Karnataka.
The nursing mothers, who have already delivered a child in recent period, may prefer to avoid or delay future pregnancy, or may not even have given a thought about it. Among those who prefer to delay next pregnancy, many are unaware of family planning practices. This is mainly influenced by the prevailing sociodemographic factors in their families. To study the prevailing Knowledge, Attitude and Practice of contraception and the influence of sociodemographic factors on family planning practices among the healthy nursing mothers. A cross-sectional study was conducted among 2500 healthy breast feeding mothers who delivered at Medical College Hospital (MCH), Vijayanagara Institute of Medical Sciences(VIMS), Bellary during Dec 2011 to Nov 2013. They were interviewed using a pre structured questionnaire in the post natal wards on 2(nd) to 7(th) postpartum day. Later these mothers were educated and counseled regarding various suitable contraceptive methods. The data collected were analysed using percentage and chi- square test. The proportion of willingness for contraception is more among women in the age group 19-29 years, among literate husband and wife, among women belonging to nuclear families and with higher socioeconomic status. Muslim women were least receptive to contraceptive advice. Regarding awareness of contraceptive methods only 46% had knowledge regarding family planning methods. A total of 43% mothers opted to limit family size. Among 16% of mothers who did not want to limit family size, 70% had no male child. In most of the families, final decision regarding family planning method was taken by husband alone or by elders. The most important reason for lack of family planning practices was lack of awareness (57.2%). Many of the nursing mothers are not aware of contraceptive practices. But these women are very receptive to contraceptive advice. Also, the decision of family planning depends not only on the couples but even on elders of the family. Hence, a combined family approach to educate and counsel the entire family including elders is needed. The major determinant is education of the entire family regarding family planning practices.


Serum IGFBP7 deriving from spleen and lung could be used for early recognition of cardiac surgery-associated acute kidney injury.
The utility of arithmetic product of urinary tissue metalloproteinase inhibitor 2 (TIMP2) and insulin-like growth factor-binding protein 7 (IGFBP7) concentrations has been widely accepted on early diagnosis of acute kidney injury (AKI). However, which organ is the main source of those two factors and how the concentration of IGFBP7 and TIMP2 changed in serum during AKI still remain to be defined. In mice, gene transcription and protein levels of IGFBP7/TIMP2 in the heart, liver, spleen, lung, and kidney were measured in both ischaemia-reperfusion injury (IRI)- and cisplatin-induced AKI models. Serum IGFBP7 and TIMP2 levels were measured and compared in patients before cardiac surgery, and at inclusion (0 h), 2 h, 6 h and 12 h after Intensive Care Unit (ICU) admission, and compared with serum creatinine, blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR) and serum uric acid (UA). In mouse IRI-AKI model, compared with the sham group, the expression levels of IGFBP7 and TIMP2 did not change in the kidney, but significantly upregulated in the spleen and lung. Compared with patients who did not develop AKI, the concentration of serum IGFBP7 at as early as 2 h after ICU admission (s[IGFBP7]-2 h) was significantly higher in patients who developed AKI. The relationships between s[IGFBP7]-2 h in AKI patients and log2(SCr), log2(BUN), log2(eGFR), and log2(UA) were statistically significant. The diagnostic performance of s[IGFBP7]-2 h measured by the macro-averaged area under the receiver operating characteristic curve (AUC) was 0.948 ([95% CI], 0.853 to 1.000; P<0.001). The spleen and lung might be the main source of serum IGFBP7 and TIMP2 during AKI. The serum IGFBP7 value demonstrated good predictive accuracy for AKI following cardiac surgery within 2 h after ICU admission.


Codonopsis pilosula Polysaccharide Attenuates Tau Hyperphosphorylation and Cognitive Impairments in hTau Infected Mice.
Codonopsis pilosula polysaccharide (CPPs), a natural products with potentially lower toxicity and better bioavailability has been used in traditional Chinese medicine for 1000s of years and a neuroprotective polysaccharide mitigates tau pathology in Alzheimer's disease (AD) mouse model. However, whether CPPs can relieve AD pathology and cognitive defects remains poorly understood. Here we reported that CPPs remarkably increased the cell viability and PP2A activity, decreased tau phosphorylation in HEK 293/tau cells. Next, we employed an adeno-associated virus serotype 2 (AAV2)-induced expression of human full length tau (hTau) in C57/BL6 mice to mimic AD tau pathology. One month intragastric administration of CPPs significantly increased PP2A activity and reduced tau phosphorylation at Ser199, Ser202/Thr205 (AT8) and Thr231 in hippocampus of AAV2-hTau infected mice. Furthermore, behavioral tests revealed that CPPs rescued hTau overexpression induced cognitive defects while CPPs significantly increased the fEPSP slope and synaptic proteins including synaptotagmin and synaptophysin. Together, our data suggest that CPPs might prevent AD-like tau hyperphosphorylation via activation of PP2A and attenuates AD-like cognitive impairments through restoring the synaptic plasticity and synaptogenesis. In conclusion, our findings suggest that CPPs might be a potential candidate compound for the treatment of tau related diseases.


Genetic basis of hindlimb loss in a naturally occurring vertebrate model.
Here we genetically characterise pelvic finless, a naturally occurring model of hindlimb loss in zebrafish that lacks pelvic fin structures, which are homologous to tetrapod hindlimbs, but displays no other abnormalities. Using a hybrid positional cloning and next generation sequencing approach, we identified mutations in the nuclear localisation signal (NLS) of T-box transcription factor 4 (Tbx4) that impair nuclear localisation of the protein, resulting in altered gene expression patterns during pelvic fin development and the failure of pelvic fin development. Using a TALEN-induced tbx4 knockout allele we confirm that mutations within the Tbx4 NLS (A78V; G79A) are sufficient to disrupt pelvic fin development. By combining histological, genetic, and cellular approaches we show that the hindlimb initiation gene tbx4 has an evolutionarily conserved, essential role in pelvic fin development. In addition, our novel viable model of hindlimb deficiency is likely to facilitate the elucidation of the detailed molecular mechanisms through which Tbx4 functions during pelvic fin and hindlimb development.


Mesenchymal stem cells in osteoarthritis.
Accumulating evidence indicates that every tissue contains stem cells. Our understanding of the biology of stem cells reveals that these cell populations have a critical role in the homeostasis and repair of tissues. Besides the local stem cell niches, additional compartments in the body such as the bone marrow may serve as reservoirs for stem cell populations. On more extensive tissue damage, and guided by local repair responses, "reparative" cell populations are mobilized from more distant stem cell reservoirs and migrate to the site of injury, thereby contributing in many aspects of local tissue repair. Osteoarthritis has long been regarded as an imbalance between destructive and reparative processes. The lack of repair of the weight-bearing articular cartilage and the associated subchondral bone changes are considered of critical importance in the progression of the disease. Recent findings indicate a depletion and/or functional alteration of mesenchymal stem cell populations in osteoarthritis. These preliminary data suggest that in joint diseases such as osteoarthritis, it is of importance to investigate further the involvement of the stem cell pool in the mechanisms contributing to joint homeostasis and driving disease progression. In view of the emerging body of evidence pointing to a potential therapeutic utility of stem cell technology, it is not surprising that local delivery of mesenchymal stem cells has been explored as a therapeutic approach in animal models of osteoarthritis.


A phase I clinical trial of vaccination with KIF20A-derived peptide in combination with gemcitabine for patients with advanced pancreatic cancer.
KIF20A (RAB6KIFL) belongs to the kinesin superfamily of motor proteins, which play critical roles in the trafficking of molecules and organelles during the growth of pancreatic cancer. Immunotherapy using a previously identified epitope peptide for KIF20A is expected to improve clinical outcomes. A phase I clinical trial combining KIF20A-derived peptide with gemcitabine (GEM) was therefore conducted among patients with advanced pancreatic cancer who had received prior therapy such as chemotherapy and/or radiotherapy. GEM was administered at a dose of 1000 mg/m(2) on days 1, 8, and 15 in a 28-day cycle. The KIF20A-derived peptide was injected subcutaneously on a weekly basis in a dose-escalation manner (doses of 0.5, 1, and 3 mg/body; 3 patients/cohort). Safety and immunologic parameters were assessed. No severe adverse effects of grade 3 or higher related to KIF20A-derived peptide were observed. Of the 9 patients who completed at least one course of treatment, interferon-γ (IFN-γ)-producing cells were induced in 4 of 9 patients (P2, P3, P6, and P7), and IFN-γ-producing cells were increased in 4 of the 9 patients (P1, P5, P8, and P9). Four of the 9 patients achieved stable disease. The disease control rate was 44%. The median survival time after first vaccination was 173 days and 1-year survival rate was 11.1%. IFN-γ-producing cells were induced by the KIF20A-derived peptide vaccine at a high rate, even in combination with GEM. These results suggest that this combination therapy will be feasible and promising for the treatment of advanced pancreatic cancer.


Effective activity of cytokine-induced killer cells against autologous metastatic melanoma including cells with stemness features.
We investigate the unknown tumor-killing activity of cytokine-induced killer (CIK) cells against autologous metastatic melanoma and the elusive subset of putative cancer stem cells (mCSC). We developed a preclinical autologous model using same patient-generated CIK cells and tumor targets to consider the unique biology of each patient/tumor pairing. In primary tumor cell cultures, we visualized and immunophenotypically defined a putative mCSC subset using a novel gene transfer strategy that exploited their exclusive ability to activate the promoter of stemness gene Oct4. The CIK cells from 10 patients with metastatic melanoma were successfully expanded (median, 23-fold; range, 11-117). Primary tumor cell cultures established and characterized from the same patients were used as autologous targets. Patient-derived CIK cells efficiently killed autologous metastatic melanoma [up to 71% specific killing (n = 26)]. CIK cells were active in vivo against autologous melanoma, resulting in delayed tumor growth, increased necrotic areas, and lymphocyte infiltration at tumor sites. The metastatic melanoma cultures presented an average of 11.5% ± 2.5% putative mCSCs, which was assessed by Oct4 promoter activity and stemness marker expression (Oct4, ABCG2, ALDH, MITF). Expression was confirmed on mCSC target molecules recognized by CIK cells (MIC A/B; ULBPs). CIK tumor killing activity against mCSCs was intense (up to 71%, n = 4) and comparable with results reported against differentiated metastatic melanoma cells (P = 0.8). For the first time, the intense killing activity of CIK cells against autologous metastatic melanoma, including mCSCs, has been shown. These findings move clinical investigation of a new immunotherapy for metastatic melanoma, including mCSCs, closer.


Understanding Barriers to Access and Utilization of Developmental Disability Services Facilitating Transition.
To explore the barriers faced by parents of individuals with intellectual and developmental disabilities when obtaining and using Developmental Disability Services (DDS) to support adolescent transition. The authors conducted a basic interpretive qualitative study using semistructured interviews. Interviews were manually coded by the team of university-based researchers using constant comparative analysis. The codes were grouped into themes. Thematic saturation occurred after 18 interviews with parents (n = 10) and service coordinators for DDS (n = 8). Barriers to DDS enrollment included emotional and administrative burden, fear of invasion of privacy, lack of a qualifying diagnosis, difficulties in accessing information about services, and misinformation about services. Barriers to DDS use once enrolled were difficulty in finding/hiring direct support professionals, high turnover of direct support professionals, and lack of training and skill among direct support professionals. Participants also noted high turnover among service coordinators, further administrative burden from hiring direct support professionals, and required home visits by service coordinators as additional barriers to service use. Participants reported benefits of DDS including increased inclusion for clients in the community, the use of person-centered skill building, and access to respite care and system navigation support. Although all participants reported benefits of acquiring services, there are significant barriers to acquiring and maintaining these services. Recommendations based on these barriers are provided for DDS, federal policy makers, and local support professionals along with a toolkit of potential strategies to support families.


Calcium ions and osteoclastogenesis initiate the induction of bone formation by coral-derived macroporous constructs.
Coral-derived calcium carbonate/hydroxyapatite macroporous constructs of the genus Goniopora with limited hydrothermal conversion to hydroxyapatite (7% HA/CC) initiate the induction of bone formation. Which are the molecular signals that initiate pattern formation and the induction of bone formation? To evaluate the role of released calcium ions and osteoclastogenesis, 7% HA/CC was pre-loaded with either 500 μg of the calcium channel blocker, verapamil hydrochloride, or 240 μg of the osteoclast inhibitor, biphosphonate zoledronate, and implanted in the rectus abdominis muscle of six adult Chacma baboons Papio ursinus. Generated tissues on days 15, 60 and 90 were analysed by histomorphometry and qRT-PCR. On day 15, up-regulation of type IV collagen characterized all the implanted constructs correlating with vascular invasion. Zoledronate-treated specimens showed an important delay in tissue patterning and morphogenesis with limited bone formation. Osteoclastic inhibition yielded minimal, if any, bone formation by induction. 7% HA/CC pre-loaded with the Ca(++) channel blocker verapamil hydrochloride strongly inhibited the induction of bone formation. Down-regulation of bone morphogenetic protein-2 (BMP-2) together with up-regulation of Noggin genes correlated with limited bone formation in 7% HA/CC pre-loaded with either verapamil or zoledronate, indicating that the induction of bone formation by coral-derived macroporous constructs is via the BMPs pathway. The spontaneous induction of bone formation is initiated by a local peak of Ca(++) activating stem cell differentiation and the induction of bone formation.


Effect of growth hormone on the immune function of dendritic cells.
Dendritic cells (DCs) are one of the most important antigen presenting cells in the human body, and DCs at various stages of maturation possess different or even opposite functions. The aim of this study was to investigate the influence of growth hormones on the functional status of cord blood-derived DCs encompassing immunophenotype, ability to excrete interleukin (IL)-12 and provoke autologous leukomonocyte. Mononuclear cells were isolated from fresh cord blood, with IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF) used to induce and stimulate the mononuclear cells. Growth hormone at different concentrations was used to modify DCs, and then DCs morphology, number and growth status were observed. The immunophenotype of DCs was detected with a flow cytometer. The concentration of IL-12 in the DCs supernatant was determined by enzyme linked immunosorbent assay (ELISA) and DCs functional status was evaluated by autologous mixed lymphocyte reactions. Mononuclear cells from cord blood can be differentiated into DCs by cytokine induction and growth hormone modification. With the increase in growth hormone concentrations (5 - 100 microg/L), the expression of DCs HLA-DR, CD1alpha, CD80 and CD83 were significantly increased (P < 0.05). The ability of DCs to secrete IL-12 was significantly improved (P < 0.05), and the ability of DCs to activate autologous lymphocytes was significantly enhanced (P < 0.05). Pegvisomant was able to ablate the effects of growth hormone on DCs. Growth hormone may facilitate DCs induction and maturation, and improve the reproductive activity of autologous lymphocytes in a dose-dependent manner. Growth hormone may serve as a factor of modifying DCs to achieving maturity.


ESHRE PGD Consortium data collection VIII: cycles from January to December 2005 with pregnancy follow-up to October 2006.
The eighth report of the European Society of Human Reproduction and Embryology PGD Consortium is presented documenting cycles collected for the calendar year 2005 and follow-up of the pregnancies and babies born until October 2006 which resulted from these cycles. For the first time, the delivery rates for each indication are presented and also the pregnancy rates for each centre are reported anonymously. Since the first data collections, there has been a steady increase in the number of cycles, pregnancies and babies reported annually. For data collection VIII, 39 centres have participated, reporting on 3488 cycles to oocyte retrieval (OR), along with details of the follow-up on 845 pregnancies and 670 babies born. Five hundred and twenty OR were reported for chromosomal abnormalities, 108 OR for sexing for X-linked diseases, 500 OR for monogenic diseases, 2275 OR for preimplantation genetic screening and 85 OR for social sexing. Data VIII is compared with the cumulative data for data collections I-VII.


The use of radiolabelled triostin antibiotics to measure low levels of binding to deoxyribonucleic acid.
Triostin antibiotics, which contain a cyclic peptide with a disulphide bridge, have been prepared by growing Streptomyces triostinicus in the presence of inorganic [35S]-sulphate. The labelled triostin A has been shown to behave in all respects similarly to the authentic natural product and to enable a much more sensitive radiochemical adaptation of the solvent-partition method for determining antibiotic binding to DNA. By this means, binding isotherms at low, biologically relevant levels (down to one antibiotic molecule per gene) have been measured. The results indicate the existence of some tight binding sites in natural DNA species that are preferentially occupied at low concentrations. No evidence has been found for any allosteric transitions provoked by interaction between these antibiotics and natural DNA species, though there is evidence for co-operativity in the binding of triostin A to poly(dA-dT). For the first time accurate isotherms have been determined for the binding of triostin C to DNA; its binding constants for a variety of polydeoxynucleotides are uniformly tighter than those of triostin A but fall into the same ranking order when different species of natural DNA are compared.


Energy balance components in persons with paraplegia: daily variation and appropriate measurement duration.
Despite obesity being highly prevalent in persons with spinal cord injury (SCI), our current understanding of the interactions between energy balance components, which may contribute to this, is limited. The primary aim of this study is to identify the intra-individual variability of physical activity dimensions across days and suggest an appropriate monitoring time frame for these constructs in adults with SCI. The secondary aim is to examine these parameters with regard to energy intake and dietary macronutrient composition. Participants [33 men and women with chronic (> 1 year post injury) paraplegia; age = 44 ± 9 years (mean ± S.D.] wore an Actiheart™ PA monitor and completed a weighed food diary for 7 consecutive days. Spearman-Brown Prophecy Formulae, based on Intraclass Correlations of .80 (acceptable reliability), were used to predict the number of days required to measure energy balance components. Linear mixed-effects analyses and magnitude-based inferences were performed for all energy intake, expenditure and physical activity dimensions. Adjustments were made for age, injury level, wear time, sex, day of the week and measurement order as fixed effects. To reliably measure energy expenditure components; 1 day [total energy expenditure (TEE)], 2 days [physical activity energy expenditure (PAEE), light-intensity activity, moderate-to-vigorous PA (MVPA)], 3 days [physical activity level (PAL)] and 4 days (sedentary behaviour) are necessary. Device wear time (P < 0.02), injury level (P < 0.04) and sex (P < 0.001) were covariates for energy expenditure components. Four and ≤24 days are required to reliably measure total energy intake (kcal) and diet macronutrient composition (%), respectively. Measurement order (from day 1-7) was a covariate for total energy intake (P = 0.01). This is the first study to demonstrate the variability of energy intake and expenditure components in free-living persons with chronic (> 1 year) paraplegia and propose suitable measurement durations to achieve acceptable reliability in outcome measures. Device wear time and measurement order play a role in the quality of energy expenditure and intake data, respectively, and should be considered when designing and analysing studies of energy balance components in persons with SCI. N/A.


Early postoperative evaluation of secondary bone grafting into the alveolar cleft and its effects on subsequent orthodontic treatment.
Alveolar bone grafting is a standard procedure used to achieve good occlusion for both functional and aesthetic purposes in patients with cleft lip and palate. At the past, main methods used to evaluate bone bridge formation after bone grafting are radiographs, such as dental, occlusal, and panoramic. To evaluate bone bridge both qualitatively and quantitatively, we used CT scans (conventional and QCT). Quantitative computed tomography (QCT) has previously been used for measuring bone mineral density of the lumbar vertebrae. The study comprised 26 male and 15 female patients who underwent alveolar bone grafting. We analyzed bone bridge with regard to four factors: marginal bone level, vertical height, anteroposterior bone width and bone mineral density using dental radiographs, and CT scans such as conventional and QCT. The clinical results of orthodontic treatment were evaluated more than 2 years postoperatively. Orthodontic treatment was considered to be successful when the bone bridge satisfied the following criteria: marginal bone level >= 3, vertical height >= 6.5 mm, anteroposterior bone width >= 5 mm, and bone mineral density < 350 mg Ca(5) (PO(4)) OH/mL. we could predict the prognosis of patients' orthodontic treatment in early stage after bone grafting.


Laparoscopic restorative proctocolectomy with ileal S-pouch.
Restorative proctocolectomy has revolutionized the surgical management of ulcerative colitis and familial polyposis syndromes. Though now evolved to include laparoscopy, this approach has not included alternative pouch designs such as ileal S-pouch reconstruction. This comparative analysis evaluated the combination of laparoscopic-assisted total proctocolectomy with an ileal S-pouch design. One hundred fifty-six (65 laparoscopic-assisted) total proctocolectomy and ileal S-pouch-anal anastomosis procedures performed between 2003 to 2007 were identified from a prospective surgical database. Operative time, length of incision, length of hospital stay, complications, and return of bowel function were examined. A cost analysis including preoperative through postoperative hospital stay and operating room and postanesthesia care unit costs was performed. The laparoscopic-assisted total proctocolectomy and ileal S-pouch-anal anastomosis procedures were performed for ulcerative colitis in 60 cases and familial adenomatous polyposis in the remaining 5 patients. Four conversions to open technique occurred (6 percent). Comparing laparoscopic and open procedures, the laparoscopic approach took longer to perform than the open technique (mean 451 minutes vs. 347 minutes open; P < 0.001). The mean hospital stay was 6.3 days in the laparoscopic group vs. 8.2 days in the open group (P < 0.001). A detailed cost analysis revealed similar overall costs between the laparoscopic ($18,700) and open approaches ($18,500). Use of a laparoscopic total proctocolectomy with ileal S-pouch-anal anastomosis reconstruction minimizes incision size and shortens hospital stay. At a teaching academic institution, the laparoscopic approach requires longer operative times yet a negligible cost disadvantage.


Is franchising in health care valuable? A systematic review.
Franchising is an organizational form that originates from the business sector. It is increasingly used in the healthcare sector with the aim of enhancing quality and accessibility for patients, improving the efficiency and competitiveness of organizations and/or providing professionals with a supportive working environment. However, a structured overview of the scientific evidence for these claims is absent, whereas such an overview can be supportive to scholars, policy makers and franchise practitioners. This article provides a systematic review of literature on the outcomes of franchising in health care. Seven major databases were systematically searched. Peer-reviewed empirical journal articles focusing on the relationship between franchising and outcomes were included. Eventually, 15 articles were included and their findings were narratively synthesized. The level of evidence was rated by using the Grading of Recommendations Assessment, Development, and Evaluation scale. The review shows that outcomes of franchising in health care have primarily been evaluated in low- and middle-income countries in the reproductive health/family planning sector. Articles about high-income countries are largely absent, apart from three articles evaluating pharmacy franchises. Most studies focus on outcomes for customers/clients and less on organizations and professionals. The evidence is primarily of low quality. Based on this evidence, franchising is predominantly positively associated with client volumes, physical accessibility and some types of quality. Findings regarding utilization, customer loyalty, efficiency and results for providers are mixed. We conclude that franchising has the potential to improve outcomes in healthcare practices, but the evidence base is yet too weak for firm conclusions. Extensive research is needed to further determine the value of healthcare franchising in various contexts. We advocate more research in other healthcare sectors in both low- and middle-income countries and high-income countries, on more types of outcomes with attention to trade-offs, and on what factors produce those outcomes.


Prognostic value of thyroglobulin after thyroidectomy before ablative radioiodine therapy in thyroid cancer.
Serum thyroglobulin (Tg) is a suitable marker for differentiated thyroid carcinoma after total thyroid ablation by surgery and 131I therapy. Before the first 131I treatment, Tg is not a reliable tumor marker since it can also originate from remnant tissue. It was hypothesized that the ratio of serum Tg to 131I uptake in the thyroid bed could be used to correct Tg values for variations in remnant tissue. The hypothesis was evaluated in 111 patients with differentiated thyroid cancer (38 follicular/73 papillary). Tg and 131I uptake in the thyroid bed were measured before the first 131I therapy. The ratio of Tg to 131I uptake was determined in four groups: Group A, tumor free (n = 81); Group B, lymph node metastases (n = 11); Group C, distant metastases (n = 11); Group D, later recurrence [during a mean follow-up of 56 mo; (n = 8)]. Wilcoxon two-sample test was performed to determine statistical significance between Group A and Groups B-D. Significant differences in the Tg/131I uptake ratios (median) between Group A (1.0 ng/ml/%) and Groups B (3.3 ng/ml/%) and D (3.3 ng/ml/%) were observed (p < 0.01). In tumor-free patients (Group A), there was no value higher than 5.7 ng/ml/%. Therefore, a higher ratio, observed in 14 of the 30 remaining patients, was indicative of metastases or later recurrence. The ratio of serum Tg to 131I uptake in the thyroid bed might be used as a prognostic marker for thyroid cancer before implementing ablation with 131I.


Learning and sleep-dependent consolidation of spatial and procedural memories are unaltered in young men under a fixed short sleep schedule.
To investigate if a fixed short sleep schedule impairs one of the main functions of sleep, which is to consolidate newly learned memories. Sixteen young men participated in two experimental conditions, each of which lasted for 3 consecutive days and nights in our laboratory: a short sleep schedule (4.25-h sleep opportunity per night) versus a normal sleep schedule (8.5h per night). In the evening after two experimental nights, participants learned locations of 15 card pairs (spatial memory task) and a procedural finger tapping sequence task. Post-sleep retrieval of both memory tasks was tested the next morning. The short sleep schedule, compared with the normal sleep schedule, considerably altered sleep characteristics, e.g. the proportion of time in slow-wave sleep increased across the three experimental nights. In contrast, neither learning in the evening of day 2, nor subsequent overnight memory consolidation (i.e. concerning the change in memory performance between pre-sleep learning on day 2 and post-sleep retrieval on day 3) differed between the normal and short sleep schedule conditions. Our findings suggest that learning in the evening and subsequent sleep-dependent consolidation of procedural and spatial memories are unaltered in young men living under a fixed short sleep schedule. Future studies are warranted to validate our findings in other groups (e.g. adolescents and older subjects) and after more prolonged chronic sleep loss paradigms.


Stratospheric ozone destruction by man-made chlorofluoromethanes.
Calculations indicate that chlorofluoromethanes produced by man can greatly affect the concentrations of stratospheric ozone in future decades. This effect follows the release of chlorine from these compounds in the stratosphere. Present usage levels of chlorofluoromethanes can lead to chlorine-catalyzed ozone destruction rates that will exceed natural sinks of ozone by 1985 or 1990.


Change in psoriatic arthritis outcome measures impacts SF-36 physical and mental component scores differently: an observational cohort study.
The objective was to investigate interplay and physical and mental component scores between change (Δ) in health-related quality of life (HRQoL) quantified by the physical component score (PCS) and mental component score (MCS) retrieved from short-form health survey (SF-36), change in disease activity (ΔDAS28CRP) and manifestations of PsA. PsA patients initiating new medical therapy were enrolled. Independent disease measures evaluating disease activity, enthesitis, psoriasis, pain and fatigue were collected at treatment initiation and after 4 months. Interplay between independent disease measures and dependent outcome measures, ΔPCS and ΔMCS, was described with univariate regression analyses. Multivariate regression analyses were applied to assess the impact of independent variables, such as individual disease outcome measures vs ΔDAS28CRP on ΔPCS and ΔMCS. One hundred and eight PsA patients were included. In the univariate regression analyses, improvement in fatigue, pain and disability were associated with improvement in ΔPCS (β; -2.08, -0.18 and -13.00, respectively; all P < 0.001) and ΔMCS (β; -1.59, -0.12 and -6.07, respectively; P < 0.001, P < 0.001 and P = 0.003, respectively). When patient-reported outcomes were included in the final multivariate models, improvements in ΔPCS and ΔMCS were associated with improvements in pain, fatigue and disability (P < 0.001). Improvement in enthesitis impacted ΔPCS positively (β -0.31, P < 0.001). No association was found between change in skin psoriasis, ΔPCS and ΔMCS (β 0.15, P = 0.056 and β 0.05, P = 0.561, respectively). In this PsA patient cohort, diminishing pain, disability and fatigue improved PCS and MCS significantly. Changes in enthesitis and psoriasis did not grossly impact HRQoL compared with DAS28CRP. Individual PsA manifestations influence HRQoL differently, which is important clinically when targeting treatment. ClinicalTrials.gov, http://clinicaltrials.gov, NCT02572700.


Results of replantation of amputated fingertips in 450 patients.
Over a 15-year period (August, 1988 to May 2003), the authors have carried out 510 replantations of amputated fingertips distal to the nail base (zone I) in 450 patients, with a high overall survival rate (92 percent), using combinations of arterial and venous anastomoses without any alternative methods such as "pocketing." Replantations that anastomosed only one artery (25 digits) had a success rate of 68 percent, one artery and one vein (115 digits) had a success rate of 82 percent, one artery and two veins (240 digits) had a success rate of 95 percent and more than two artery and vein anastomoses (130 digits), had a success rate of 99 percent. The follow-up period ranged from 3 months to 14 years and 432 patients were followed-up more than 6 months. In these latter patients, the average two-point discrimination was 7 mm.


Peer networks among heavy, regular and infrequent drinkers prior to marriage.
Research has consistently demonstrated that, among adolescents, the characteristics of one's peers are important predictors of substance abuse. The impact of the peer network on adult drinking, however, has received considerably less attention. The purpose of the present study was to examine social network characteristics that are associated with heavy drinking in adulthood prior to marriage. Couples were recruited at the time of their first marriage. Husbands and wives were each given identical questionnaire packets to complete at home, independently, as well as a postage-paid envelope for packet return. A broad range of constructs was assessed; included were personality characteristics, relationship functioning, drinking behavior and social network characteristics. Complete data were obtained from 471 husbands and 471 wives. The social networks of heavy-drinking men, compared to men drinking regularly or infrequently, were younger, more likely to be male and unmarried and consisted of friends rather than family or others. For both men and women, "drinking buddies" accounted for nearly 75% of the heavy drinkers' peer networks. The overall ratings of support and conflict created by peers did not differ according to drinking group, for either men or women. Prior to marriage, the social networks of heavy drinkers differ considerably from the networks of regular or infrequent drinkers with regard to the drinking patterns of their peers. An important finding was that heavy drinkers appear to experience a similar level of emotional, financial and practical support from their peer network compared to regular or infrequent drinkers.


Probiotics as adjunctive treatment for chronic rhinosinusitis: a randomized controlled trial.
To determine if oral probiotics as adjunctive treatment are more effective than placebo in improving quality of life in patients with chronic inflammatory rhinosinusitis. Prospective, randomized, double-blind, placebo-controlled trial. A total of 77 patients with chronic inflammatory rhinosinusitis were randomly assigned to receive oral probiotic Lactobacillus rhamnosus R0011 strain (500 million active cells/tablet twice daily) (n = 39) or oral placebo treatment (n = 38) for 4 weeks. In the probiotic group, the mean change from baseline in the SNOT-20 scores was significant at 4 weeks (P = 0.002) but not at 8 weeks (P = 0.37). Rhinological domain improved by 9.3 percent (P = 0.004) in probiotics group but returned to baseline level at 8 weeks. No significant differences were found between the probiotic and placebo groups in mean changes from baseline to 4 weeks (P = 0.79) or from baseline to 8 weeks (P = 0.23). No changes in symptom frequency were noted, either within each group or between treatment groups at 4 and 8 weeks. There was no difference in medication use or side effects between the two study groups. Oral use of the probiotic strain L rhamnosus R0011 did not improve sinonasal quality-of-life scores in patients with chronic inflammatory rhinosinusitis compared with placebo.


[Elucidation of accelerated blood clearance phenomenon caused by repeat injection of PEGylated nanocarriers].
Liposomes modified with polyethylene glycol (PEG) can stably exist in the bloodstream because the PEG on the liposomes attracts a water shell to the liposomal surface. Since these liposomes are long circulating nanocarriers, they are used as drug and gene delivery tools. Repeat injection of PEGylated liposomes, however, is known to induce the accelerated blood clearance (ABC) phenomenon. In the ABC phenomenon, PEGylated liposomes that are injected subsequent to the first injection are cleared rapidly from the bloodstream and accumulate in the liver, resulting in loss of their long-circulating characteristics. The induction of ABC phenomenon is related to the production of anti-PEG IgM from splenic B cells. To elucidate the mechanism of the phenomenon, we firstly examined the relationship between the induction of ABC phenomenon and the concentration of PEGylated liposomes, and observed that the high dose of those did not induce the phenomenon. Next, we investigated whether polymeric micelles trigger ABC phenomenon or not. Finally, the size-dependency of ABC phenomenon was investigated by use of variously sized PEGylated liposomes and polymeric micelles having PEG chains. Our data suggest that the initiation of ABC phenomenon would be size-dependent, and particles smaller than 30 nm did not induce ABC phenomenon. We anticipate that the elucidation of the ABC phenomenon will be helpful for the development of DDS formulations.


Covalent, sequence-specific attachment of long DNA molecules to a surface using DNA-templated click chemistry.
We present a novel method that covalently and sequence-specifically attaches long DNA molecules to a surface that is compatible with high-resolution atomic force microscopy (AFM) imaging. Surfaces prepared with this approach are ideally suited for performing biophysical experiments on single DNA molecules.


Alarm pheromones and chemical communication in nymphs of the tropical bed bug Cimex hemipterus (Hemiptera: Cimicidae).
The recent resurge of bed bug infestations (Cimex spp.; Cimicidae) and their resistance to commonly used pesticides calls for alternative methods of control. Pheromones play an important role in environmentally sustainable methods for the management of many pest insects and may therefore be applicable for the control of bed bugs. The tropical bed bug, Cimex hemipterus, is a temporary ectoparasite on humans and causes severe discomfort. Compared to the common bed bug, Cimex lectularius, little is known about the chemical signalling and pheromone-based behaviour of the tropical species. Here, we show that the antennal morphology and volatile emission of C. hemipterus closely resembles those of C. lectularius and we test their behavioural responses to conspecific odour emissions. Two major volatiles are emitted by male, female and nymph C. hemipterus under stress, (E)-2-hexenal and (E)-2-octenal. Notably, nymph emissions show contrasting ratios of these compounds to adults and are further characterized by the addition of 4-oxo-(E)-2-hexenal and 4-oxo-(E)-2-octenal. The discovery of this nymph pheromone in C. hemipterus is potentially the cause of a repellent effect observed in the bio-tests, where nymph odours induce a significantly stronger repellent reaction in conspecifics than adult odours. Our results suggest that pheromone-based pest control methods developed for C. lectularius could be applicable to C. hemipterus, with the unique nymph blend showing promising practical properties.