Levels Of DP Research Articles

Assessment of Burnout Among Emergency Medicine Residents in Saudi Arabia: A Cross-Sectional Survey

Background: Burnout syndrome is a frequent challenge faced in the emergency department. There exists a dearth of clinical evidence regarding the risk and occurrence of burnout, among emergency residents in Saudi Arabia. Therefore, this study was conducted to assess the parameters of burnout in this cohort. Methods: This prospective, cross-sectional study was conducted via an online survey using Maslach Burnout Inventory for Healthcare Professionals (MBI-HSS) questionnaire. All emergency medicine residents registered under the country's residency program were invited to participate. The relative importance index (RII) analysis was used to describe the frequency of the MBI-HSS indicators. The t-test of independent groups and the one-way analysis of variance were used to assess the impact of demographic and professional factors. Results: A total of 73 residents completed the questionnaire. Low PA was reported by 53.4% while medium to high DP and EE were reported by 84.9% and 67.1% residents respectively. Female residents had significantly higher EE versus males. Age, marital status and number of children had no correlation with burnout. Emergency residents serving at hospitals of the Ministry of Health reported significantly higher levels of burnout, versus other institutions. The final year of the residency program showed significantly lower levels of burnout than the earlier years. Conclusion: This is the first study from Saudi Arabia, assessing the parameters of burnout, specifically among emergency medicine residents. The study has shown alarmingly high levels of DP, EE and low PA and warrants urgent remedial measures to curb burnout among emergency residents.

Assessment of Burnout Among Emergency Medicine Residents in Saudi Arabia: A Cross-Sectional Survey

Background: Burnout syndrome is a frequent challenge faced in the emergency department. There exists a dearth of clinical evidence regarding the risk and occurrence of burnout, among emergency residents in Saudi Arabia. Therefore, this study was conducted to assess the parameters of burnout in this cohort. Methods: This prospective, cross-sectional study was conducted via an online survey using Maslach Burnout Inventory for Healthcare Professionals (MBI-HSS) questionnaire. All emergency medicine residents registered under the country's residency program were invited to participate. The relative importance index (RII) analysis was used to describe the frequency of the MBI-HSS indicators. The t-test of independent groups and the one-way analysis of variance were used to assess the impact of demographic and professional factors. Results: A total of 73 residents completed the questionnaire. Low PA was reported by 53.4% while medium to high DP and EE were reported by 84.9% and 67.1% residents respectively. Female residents had significantly higher EE versus males. Age, marital status and number of children had no correlation with burnout. Emergency residents serving at hospitals of the Ministry of Health reported significantly higher levels of burnout, versus other institutions. The final year of the residency program showed significantly lower levels of burnout than the earlier years. Conclusion: This is the first study from Saudi Arabia, assessing the parameters of burnout, specifically among emergency medicine residents. The study has shown alarmingly high levels of DP, EE and low PA and warrants urgent remedial measures to curb burnout among emergency residents.

The Global Prevalence and Associated Factors of Burnout among Emergency Department Healthcare Workers and the Impact of the COVID-19 Pandemic: A Systematic Review and Meta-Analysis.

Emergency medicine (EM) settings are very stressful, given the high workload, intense working environment, and prolonged working time. In turn, the rate of burnout and its three domains have been increasingly reported among healthcare workers (HCWs). Therefore, we conducted this meta-analysis to determine the prevalence and risk factors of burnout among EM HCWs. Six databases were searched in February 2023, yielding 29 articles (16,619 EM HCWs) reporting burnout or its three domains (emotional exhaustion "EE", depersonalization "DP", and personal accomplishment "PA"). The primary outcome was the prevalence of burnout and its domains, while secondary outcomes included the risk factors of high burnout, EE, DP, or low PA. Burnout rates were pooled across studies using STATA software. The prevalence was measured using the pooled effect size (ES), and the random-effects model was used when heterogeneity was encountered; otherwise, the fixed-effects model was used. The prevalence of overall burnout was high (43%), with 35% of EM HCWs having a high risk of burnout. Meanwhile, 39%, 43%, and 36% of EM workers reported having high levels of EE and DP and low levels of PA, respectively. Country-specific changes in the rate of burnout were observed. The rate of high burnout, high EE, high DP, and low PA was higher during the COVID-19 pandemic as compared to the pre-pandemic period. The type of profession (nurses, physicians, residents, etc.) played a significant role in modifying the rate of burnout and its domains. However, gender was not a significant determinant of high burnout or its domains among EM workers. Burnout is a prevalent problem in emergency medicine practice, affecting all workers. As residents progress through their training years, their likelihood of experiencing burnout intensifies. Nurses are most affected by this problem, followed by physicians. Country-associated differences in burnout and its domains are evident.

The Prevalence of Physicians’ Burnout Syndrome in Ibrahim Malik Teaching Hospital, Khartoum, Sudan, 2020

Background: Burnout is described as exploratory and qualitatively as a state of emotional exhaustion due to excessive demands on energy, strength or sources in workplace. It is characterized by physical symptoms such as exhaustion, fatigue, frequent headache, and gastrointestinal disorders, sleeplessness and behavioral signs include frustration, anger, a suspicious attitude omnipotence or overconfidence, cynicism and signs of depression.
 Methods: This is a descriptive cross-sectional hospital-based study. The data was collected from 100 Physicians by a questionnaire specially prepared for the purposes of this study. Filling out the questionnaires was distributed by the research team in person. The questionnaire consisted of 27 questions, with 9 questions attributed to each of the 3 risk factors (Depersonalization, Emotional Exhaustion, and Personal Accomplishment). Data was analyzed by using SPSS program version 26 and the result was represented in tables and figures.
 Results: (72%) of the participant were females and (28 %) were males, age ranged between 2 and more than 51 years, age was categorized into three groups 20–30 (73%), 31–40 (20%) and 41–50 (5%) and more than 50 (2%). Participants were distributed in 6 different specialties with Pediatrics as the most represented specialty (18%). In the level of profession most of the participant were house officer (42%) followed by registrar (32%) and the least were specialist (4%). Levels of emotional exhaustion, depersonalization, (77 %) of the sample had a high level of (EE), (54%) had a high level of (DP), and (14 %) had a low level of (PA). (19%) of the residents included in this study had a high level of burnout in all three do- mains of the index, and (93%) had a high level in at least one of the three. The high level of each burnout components distributed according to the research different demographic variables and the results of the inferential statistical tests. Males had higher levels of EE (82.8%), and DP (55%), and lower levels of PA (14.9%) than females (71.6%), (54%), (12.1%) respectively.
 Conclusion: In conclusion, our study showed that burn out is highly prevalent among Ibrahim Malik hospital doctors, while female doctors had a higher degree burnout than males. Among the different professional levels, the highest percentage of burnout belonged to GPs and the lowest belonged to consultants .ER doctors suffered the most from burnout, whereas surgeons suffered the least. Several factors attributing to the burnout symptoms of these doctors have been identified.

Burnout syndrome in medical oncologists during the COVID-19 pandemic: Argentinian national survey.

Burnout (BO) syndrome is a condition that results in physical and mental distress. The current COVID-19 pandemic is strongly affecting the mental health of the general population. We aimed to assess the incidence of BO among medical oncologists and determine factors associated with burnout levels during the current pandemic.MethodsA digital survey was created for this study. The Spanish-validated version of Maslach BO Inventory was incorporated to define BO. Social and demographic information was analysed to remove duplicated answers.ResultsA total of 188 Argentinian medical oncologists from 16 cities participated in the survey. The median age of the participants was 43 years (IQR 38-50) and a similar distribution between male and female was observed. At the time of the survey, Argentina was in the third month of strict lockdown. Most of the participants practiced in both public and private practice facilities (55.3%) and the majority reported more than 10 years of experience (53.2%). Twenty-five percent (43) of subjects reported high levels of DP, 39.9% (75) reported high levels of EE and 53.7% (101) reported low levels of PA. BO Maslach criteria were fulfilled by 14.9% (28). We compared this result with other burnout assessment tools. Using the Gil-Monte and Neira tool, BO-associated domains were altered in 77.1%, 42% and 42% for EE, DP, and PA domains, respectively. Concomitantly, under Neira assessment a domain impairment was appreciated in 77.1%, 76% and 54% respectively. BO criteria were met by 30.3% (57) according to Gil-Monte and 47.9% (90) to Neira.ConclusionBO is a multifaceted issue with a negative impact on physicians, patients, and institutions. During the COVID-19 pandemic, BO criteria was met in a considerable proportion of survey respondents using MBI, and Peiro and Neiro tools and younger age, use of antidepressants and psychological medications and income reduction arose as statistically significant factors after multivariate analysis.

The roles of child maltreatment types and peer relationships on behavior problems in early adolescence

BackgroundAlthough previous research has established that child maltreatment (CM) and peer relationships (i.e., deviant peer affiliation, being ignored by peers) are strong predictors of adolescent internalizing (INT) and externalizing (EXT) behavior problems, no study has examined the above effects concurrently. Nor have researchers investigated the potential peer relationship differences in the effects of CM types on adolescent behavior problems. Thus, this study aims to examine the independent and combined effects of different types of CM and peer relationships on behavior problems. MethodsThe Generalized Estimating Equations approach was conducted using the Longitudinal Studies of Child Abuse and Neglect. Child-Protective-Services reports and youth self-reports were used for each type of CM. Deviant peer affiliation (DP) has been assessed using a modified version of the Youth-Risk-Behavior-and-Monitoring-the-Future Survey, while being ignored by peers was assessed using a single question. Adolescent INT and EXT were measured using the Youth-Self-Report. ResultsEmotional abuse was associated with both INT and EXT, whereas physical abuse was associated with EXT. Higher DP and higher incidence of being ignored by peers were both associated with higher levels of INT and EXT. Emotionally abused youth with higher levels of DP had less INT, compared to emotionally abused youth with lower levels of DP. ConclusionThe Findings indicate the need for interventions that 1) take into account the different effects of CM types, specifically for emotionally abused youth; 2) help youth to build positive relationships with peers; and 3) work to reduce the possibility of affiliation with deviant peers.

Longitudinal association between deviant peer affiliation and externalizing behavior problems by types of child maltreatment

BackgroundPrevious research has documented that deviant peer affiliation (DP) and externalizing behavior problems (EXT) are highly related and often co-occur. However, the directionality of the association between DP and EXT remains debatable. In addition, few studies have examined the longitudinal effects of child maltreatment types on co-development of DP and EXT overtime. Therefore, this study examined the role of child maltreatment in predicting the co-development of DP and EXT. MethodsDP and EXT were assessed at ages 12, 14, and 16. DP was measured using 13 items from the modified version of the Youth Risk Behavior and Monitoring the Future Survey. EXT was measured using the Child Behavior Checklist. Each type of child maltreatment (birth to age 12) was assessed using the CPS substantiated cases. ResultsThe results indicated that, on average, DP increased over time, whereas EXT decreased over time. In addition, the initial levels of EXT were associated with the slope of DP. Conditional parallel-process latent growth curve modeling identified that physically abused adolescents had higher initial levels of DP and showed a slower increase in DP, while those who had been emotionally abused were associated with a steeper decrease in EXT. ConclusionThe findings offer several meaningful implications for practice. First, early assessment of and treatment for EXT may be helpful in preventing DP over time. In addition, practitioners could assess each type of maltreatment to tailor preventive interventions for early onset and ongoing development of DP and EXT.

Characterization of Magnitude and Antigen Specificity of HLA-DP, DQ, and DRB3/4/5 Restricted DENV-Specific CD4+ T Cell Responses.

Background: Dengue Virus (DENV) associated disease is a major public health problem. Assessment of HLA class II restricted DENV-specific responses is relevant for immunopathology and definition of correlates of protection. While previous studies characterized responses restricted by the HLA-DRB1 locus, the responses associated with other class II loci have not been characterized to date. Accordingly, we mapped HLA-DP, DQ, and DRB3/4/5 restricted DENV-specific CD4 T cell epitopes in PBMCs derived from the DENV endemic region Sri Lanka.Methods: We studied 12 DP, DQ, and DRB3/4/5 alleles that are commonly expressed and provide worldwide coverage >82% for each of the loci analyzed and >99% when combined. CD4+ T cells purified by negative selection were stimulated with pools of HLA-predicted binders for 2 weeks with autologous APC. Epitope reactive T cells were enumerated using IFNγ ELISPOT assay. This strategy was previously applied to identify DRB1 restricted epitopes. In parallel, membrane expression levels of HLA-DR, DP, and DQ proteins was assessed using flow cytometry.Results: Epitopes were identified for all DP, DQ, and DRB3/4/5 allelic variants albeit with magnitudes significantly lower than the ones previously observed for the DRB1 locus. This was in line with lower membrane expression of HLA-DP and DQ molecules on the PBMCs tested, as compared to HLA-DR. Significant differences between loci were observed in antigen immunodominance. Capsid responses were dominant for DRB1/3/4/5 and DP alleles but negligible for the DQ alleles. NS3 responses were dominant in the case of DRB1/3/4/5 and DQ but absent in the case of DP. NS1 responses were prominent in the case of the DP alleles, but negligible in the case of DR and DQ. In terms of epitope specificity, repertoire was largely overlapping between DRB1 and DRB3/4/5, while DP and DQ loci recognized largely distinct epitope sets.Conclusion: The HLA-DP, DQ, and DRB3/4/5 loci mediate DENV-CD4 specific immune responses of lower magnitude as compared to HLA-DRB1, consistent with their lower levels of expression. The responses are associated with distinct and characteristic patterns of immunodominance, and variable epitope overlap across loci.

PB1754 THE PERIPHERAL CD4+CD8+ T‐CELL LEVEL OF ACUTE LEUKEMIA PATIENTS AFTER HAPLO‐HSCT IS HIGHER THAN THAT OF THESE PATIENTS AFTER HLA‐IDENTICAL‐HSCT

Background:Nowadays, we generally think that the immune responses after the HLA‐haploidentical hematopoietic stem cell transplantation (haplo‐HSCT) of acute leukemia (AL) patients mainly results from the cross reactivate by donor‐derived memory T‐cells. However, the role of thymus on immune reconstitution after haplo‐HSCT is not clearly understood yet.Aims:Regarding the development of CD4‐CD8− (double negative, DN) and CD4+CD8+ (double positive, DP) T‐cell is associated with the function of thymus, we investigate the levels of DN and DP T‐cell in AL patients who have received the haplo‐HSCT or HLA‐identical hematopoietic stem cell transplantation (identical‐HSCT).Methods:In the 1st to the 12th months after hematopoietic stem cell transplantation (HSCT), the DN T‐cell and DP T‐cell levels in the peripheral blood of 77 AL patients are evaluated by flow cytometry. And 51 of these patients received haplo‐HSCT, while 26 of them received identical‐HSCT. The repeated measures one‐way ANOVA is used for statistic analysis.Results:The DP T‐cell level of AL patients after haplo‐HSCT is significantly higher than those patients after identical‐HSCT (F = 12.02, p = 0.00). however, The DN T‐cell level in these two groups of patients do not show a significantly difference (F = 0.87, p = 0.36). Furthermore, when we only look into the haplo‐HSCT group, we found that the DP T‐cell level of patients donated by the parents (n = 31) is significantly higher than that of the patients donated by the children, (n = 7, F = 6.37, p = 0.03) as well as that of the patients donated by the sister/brother(n = 13, F = 6.64, p = 0.02).Summary/Conclusion:From the data of our center, in AL patients after haplo‐HSCT show a high DP T‐cell level than these patients after identical‐HSCT, and this indicates that thymus as the human central immune organ, has a possibility to play a role in immune reconstitution after haplo‐HSCT. But the clinical significance of DP T‐cell on predicting thymus function and immune reconstitution need to be further explored with more patient data. Here, we would like to share our finding on the peripheral DP T‐cell level after haplo‐HSCT, in order to inspire further exploration with other hematologists to clarify the mechanism involve in it.

What was once essential, may become detrimental: The mediating role of depersonalization in the relationship between childhood emotional maltreatment and psychological distress in adults

ABSTRACTDepersonalization (DP) is a dissociative phenomenon, characterized by feeling “unreal” or detached from one’s own emotions, thoughts, and behavior (APA, 2013). It is considered to be a defense mechanism, employed in response to overwhelming events, whereby thoughts and emotions are suppressed in order to enhance the individual’s capacity to function in traumatic environments. DP has been found to co-occur with anxiety and depressive disorders, and childhood emotional maltreatment (EM) has been identified as an important predisposing factor. The study’s primary aim was to investigate the mediating role of DP in the relationship between childhood EM and psychological distress in young adults. Additionally, it aimed to confirm that a history of childhood EM (emotional abuse and emotional neglect) predicted current levels of DP and to explore how both a person’s attitude towards experiencing and expressing emotions (with an emphasis on the affect phobia model) and their current attachment security are related to current DP. A cross-sectional design was employed, which included young adults (N = 761) aged between 18 and 25 years. Participants completed an online survey that comprised of several self-report measures. Regression and mediation analyses were conducted. The results indicated that: (1) DP significantly mediated the relationship between childhood EM and current psychological distress; (2) that a history of EM, but no other forms of childhood abuse, significantly predicted current DP experiences; and (3) EM, attachment-related anxiety, and negative attitudes toward emotions predicted clinical cutoff levels of DP. The results are discussed in detail, including clinical implications and direction for future research.

Nutritional Evaluation of Whole and Lipid-Extracted Biomass of the Microalga Scenedesmus sp. AMDD for Animal Feeds: Simulated Ruminal Fermentation and In Vitro Monogastric Digestibility

Background: Scenedesmus sp. AMDD (S-AMDD) has been the focus of several studies to assess its potential as a feedstock for biofuels and bioremediation, while the evaluation of its potential suitability as a novel animal feed ingredient has only just begun. In an initial study, S-AMDD demonstrated rapid growth rate and biomass productivity during exponential growth phase and the resulting biomass appeared to have good potential for animal nutrition based on its attractive proximate composition, favorable essential amino acid, fatty acid and elemental profiles and lack of contaminating heavy metals. However, the total carbohydrate and fibre fractions of whole-cell and lipid-extracted S-AMDD were relatively high which could limit their digestion, particularly when fed to monogastric animals. The difference in the capacity to digest and metabolically utilize diets rich in cellulosic material (e.g., fibre) is vast between various farmed animal species. As such, knowledge on the nutritional value of novel ingredients for ruminant animals can rarely be immediately extrapolated to monogastrics and vice versa. Simulated fermentation using rumen-derived digestive fluids or in vitro digestibility using purified monogastric- derived enzymes can provide valuable information. Although not fully conclusive, results from these types of rapid assays are generally inexpensive, require smaller amounts of sample, utilize fewer or no experimental animals, avoid feed refusal issues associated with ingredient off-flavours or odours and can be effective tools for research and for routine industrial use. Objective: The present study is the second in a series of projects designed to evaluate the nutritional value of S-AMDD for animal feed applications. The main objective was to generate novel digestibility data of whole-cell and lipid-extracted S-AMDD for both ruminant and monogastric animals including ruminal organic matter digestibility (OMD), apparent metabolizable energy (aME) content, methane (CH4) production, dilute pepsin digestibility (DPD) and two-phase gastric/pancreatic digestibility of protein (GPDProtein) and energy (GPDEnergy). Methods: Simulated ruminal OMD, aME contents and CH4 production of experimental test diets containing graded levels of whole-cell and lipid-extracted S-AMDD were estimated using a modified batchculture in vitro fermentation system with total gas capture using lactating dairy cattle as rumen fluid donors. In vitro monogastric DPD and two-phase GPD were measured by incubation of whole-cell and lipid- extracted S-AMDD samples in porcine pepsin and porcine pancreatin, containing amylase, lipase and protease enzyme solutions. Results: Simulated ruminal fermentations using lactating dairy cattle as rumen fluid donors indicate that both whole-cell and lipid-extracted S-AMDD have excellent potential for use in ruminant animal feeds. Dietary inclusion of whole-cell S-AMDD at 50% forage protein replacement (equivalent to 20% of the total diet) or lipid-extracted S-AMDD at 100% forage protein replacement (equivalent to 32% of the total diet) did not significantly affect OMD or aME content of the control diet. However, OMD was marginally compromised with 100% forage protein replacement with whole-cell S-AMDD (equivalent to 40% of the total diet) relative to the 25 and 50% replacement levels, although not significantly different from the control diet. Diets containing lipid-extracted S-AMDD significantly reduced CH4 production by approximately 50% compared to the control diet (47% reduction) and those containing whole-cell SAMDD (51% reduction). Since OMD and aME content of diets containing lipid-extracted S-AMDD were unaffected relative to the control diet and whole-cell S-AMDD-containing diets, it seems clear that lipid-extracted S-AMDD contains anti-methanogenic ‘non-fatty acid’ substances that have the ability to suppress rumen methanogenic bacteria without disturbing ruminal digestion. This area warrants further exploration in vivo, especially considering the large volume of algal feed that could be produced without occupying significant land resources. In vitro monogastric digestibility using porcine enzymes indicates that lipid-extracted S-AMDD has potential for use in monogastric animal feeds. Protein and energy digestibility of this product were moderately high (75-84% and 70%, respectively), which resulted in relatively high contents of DP (30%) and DE (14 MJ kg-1). On the other hand, the digestibility of whole-cell S-AMDD was low at 52-61% and 50%, respectively resulting in lower levels of DP (15%) and DE (12 MJ kg-1). Despite the encouraging results for lipid-extracted S-AMDD, the digestibility (particularly of energy) remains marginal for monogastric animals and requires improvement through additional cost-effective cell rupture technologies or the production of algal protein concentrates.. Keywords: Microalgae, digestibility, ruminant, monogastric, protein, energy, methane.

Nutritional ecology of elk during summer and autumn in the Pacific Northwest

Nutritional ecology of elk during summer and autumn in the Pacific Northwest

An Exploratory Analysis of Kitakyushu Residential Customer Response to Dynamic Electricity Pricing

This paper introduces the characteristic of Japanese dynamic pricing model, meanwhile, summarizes the results from an exploratory analysis of about 200 households that took part in dynamic price experiment in Kitakyushu, Japan. Using hourly load data collected from smart meter, we find statistically load reduction for participants during the DP time block. With the incentive of different levels of DP, the peak demand reduction ratio changes from 6% to 14% which proved that residential customers have the potential to respond to variable price signals. In addition, we also discussed the effect of dynamic pricing which influenced by temperature. The result indicates that the size of load reduction is the largest during the extreme temperature. This paper contributes to the implementation of dynamic pricing and provides a good experience to other countries.

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Aim The presence of HLA Ab in the allograft is associated with transplant vasculopathy (TV). Ligation of HLA class I elicits signaling events and induces the remodeling of actin cytoskeleton leading to cell survival, migration and proliferation in EC. However, the mechanism by which anti-HLA class II Ab contribute to TV development is not clear. We hypothesize that HLA II ligation induces signaling cascades mediating cytoskeleton reorganization. Methods To express HLA II, human aortic EC were infected with adenoviruses encoding Class II transactivator (Ad-CIITA). Expression of HLA II was determined by flow cytometric analysis using Ab against a monomorphic epitope on HLA II or locus specific Ab against HLA-DR, DQ and DP. Ad-CIITA infected EC were stimulated with anti-HLA II Ab and protein phosphorylation was examined by Western blot. Stress fiber formation was evaluated by fluorescence microscopy in EC stained with Texas Red-phalloidin. The FAK siRNA was utilized to deplete FAK expression. Results Infection with Ad-CIITA for 2d induced expression of HLA II in 80% of EC. Staining with locus specific Ab showed HLA-DR was expressed at the highest level with comparable levels of DP and DQ. Treatment of EC with HLA II Ab significantly increased the phosphorylation of FAK, Src, ERK and p70 S6 kinase (S6K). Ligation of HLA II also significantly augmented formation of stress fibers in EC compared to isotype control IgG [Fig. 1] Knockdown of FAK attenuated phosphorylation of Src, ERK and S6K and also abolished class II-mediated stress fiber formation. Download : Download full-size image Conclusions Ab ligation of HLA II molecules stimulates signal transduction and induces actin cytoskeleton remodeling in EC in a FAK dependent manner.

Redistribution of adhering junctions in human endometrial epithelial cells during the implantation window of the menstrual cycle

The human uterine epithelium is characterised by remarkable plasticity with cyclic changes in differentiation that are controlled by ovarian steroid hormones to optimise conditions for embryo implantation. To understand whether and how cell-cell adhesion is affected, the localisation of junction proteins was studied throughout the menstrual cycle. Expression patterns were examined by immunofluorescence in 36 human endometrial specimens of different cycle stages. Antibodies against the desmosomal proteins desmoplakin 1/2 (Dp 1/2) and desmoglein 2 (Dsg 2), the adherens junction proteins E-cadherin and β-catenin and also the common junctional linker protein plakoglobin showed a strong subapical staining during the proliferative phase until the early luteal phase (day 20). In the mid- to late luteal phase, however, these junctional proteins redistributed over the entire lateral plasma membranes. In contrast, tight junction proteins (ZO-1, claudin 4) remained at their characteristic subapical position throughout the menstrual cycle. mRNA levels of Dp 1/2, E-cadherin and ZO-1 obtained by real time RT-PCR were not significantly changed during the menstrual cycle. The observed redistribution of desmosomes and adherens junctions coincides with the onset of the so called implantation window of human endometrium. We propose that this change is controlled by ovarian steroids and prepares the endometrium for successful trophoblast invasion.

Response surface and neural network models for performance of broiler chicks fed diets varying in digestible protein and critical amino acids from 11 to 17 days of age

Central composite design (CCD; 5 levels and 4 factors), response surface methodology (RSM), and artificial neural network-genetic algorithm (ANN-GA) were used to evaluate the response of broiler chicks [ADG and feed conversion ratio (FCR)] to dietary standardized ileal digestible protein (dP), lysine (dLys), total sulfur amino acids (dTSAA), and threonine (dThr). A total of 84 battery brooder units of 5 birds each were assigned to 28 diets of CCD containing 5 levels of dP (18-22%), dLys (1.06-1.30%), dTSAA (0.81-1.01%), and dThr (0.66-0.86%) from 11 to 17 d of age. The experimental results of CCD were fitted with the quadratic and artificial neural network models. A ridge analysis (for RSM models) and a genetic algorithm (for ANN-GA models) were used to compute the optimal response for ADG and FCR. For both ADG and FCR, the goodness of fit in terms of R(2) and MS error corresponding to ANN-GA and RSM models showed a substantially higher accuracy of prediction for ANN models (ADG model: R(2) = 0.99; FCR model: R(2) = 0.97) compared with RSM models (ADG model: R(2) = 0.70; FCR model: R(2) = 0.71). The ridge maximum analysis on ADG and minimum analysis on FCR models revealed that the maximum ADG may be obtained with 18.5, 1.10, 0.89, and 0.73% dP, dLys, dTSAA, and dThr, respectively, in diet, and minimum FCR may be obtained with 19.44, 1.18, 0.90, and 0.75% of dP, dLys, dTSAA, and dThr, respectively, in diet. The optimization results of ANN-GA models showed the maximum ADG may be achieved with 19.93, 1.06, 0.90, and 0.76% of dP, dLys, dTSAA, and dThr, respectively, in diet, and minimum FCR may be achieved with 18.63, 1.26, 0.84, and 0.69% of dP, dLys, dTSAA, and dThr, respectively, in diet. The results of this study revealed that the platform of CCD (for conducting growth trials with minimum treatments), RSM model, and ANN-GA (for experimental data modeling and optimization) may be used to describe the relationship between dietary nutrient concentrations and broiler performance to achieve the optimal target.

A molecular study of desmosomes identifies a desmoglein isoform switch in head and neck squamous cell carcinoma

Desmosomes, the intercellular junctions that confer strong adhesion between epithelial cells, are frequently altered in malignancy. However, a comprehensive analysis of these structures has not been carried out in oral neoplasia. Oral squamous cell carcinomas (SCCs) and pre-malignant dysplasia can be sub-classified according to their in vitro replicative lifespan, where the immortal dysplasia (ID) and carcinoma (IC) subsets have p16(ink4a) and p53 dysfunction, telomerase deregulation and genetic instability and the mortal subset (MD and MC) do not. We found that the desmosomal proteins exhibit a distinct expression pattern in oral mucosa when compared with epidermis in vivo. Microarray data from a large panel of lines revealed that the transcript levels of DSG3, DSC2/3, DP, PG and PKP1 were reduced in ID and IC. Interestingly, DSG2 was up-regulated in MC. Reduction of DSG3 and up-regulation of DSG2 were found in two independent microarray datasets. Significantly, we demonstrated that reduction of DSG3 and up-regulation of DSG2 was reversible in vitro by using RNAi-mediated knockdown of DSG2 in IC cells. The remaining desmosomal proteins were largely disrupted or internalized and associated with retraction of keratin intermediate filaments in oral SCC lines. These findings suggest dysfunction and loss of desmosomal components are common events in the immortal class of oral SCC and that these events may precede overt malignancy.

CRTH2 mediates the activation of human Th2 cells in response to PGD2 released from IgE/anti‐IgE treated nasal polyp tissue

Mast cells release mediators upon stimulation that contribute to the pathogenesis of chronic airway disease, including the recruitment and activation of Th2 lymphocytes. The objective was to determine the involvement of prostaglandin D(2) (PGD(2)) and its receptors in the chemotaxis of Th2 cells, using nasal polyp tissue. Tissue explants from ten patients with nasal polyposis were incubated with RPMI alone or RPMI containing IgE/anti-IgE for 30 min. Some samples were treated with diclofenac to inhibit the production of PGD(2). Supernatants were assayed for PGD(2) content and for their ability to promote human Th2 cell chemotaxis in the presence and absence of a CRTH2 antagonist. Transcript levels of D protanoid receptor type 1 (DP(1)), chemoattractant receptor-homologous receptor expressed on Th2 cells (CRTH2) and PGD(2) synthase were analysed by real time PCR. Increased release of PGD(2) by nasal polyp tissue treated with IgE/anti-IgE was significantly inhibited by preincubation of the tissue with diclofenac. Transcript levels of PGD(2) synthase, DP(1) and CRTH2 receptors increased after stimulation with IgE/anti-IgE. Supernatants from IgE/anti-IgE-stimulated nasal polyp tissue caused significantly increased chemotaxis of Th2 cells. The levels of PGD(2) produced and the degree of Th2 cell chemotaxis were highly correlated. Diclofenac inhibited the production of Th2 cell chemotactic activity, and the chemotactic effect of the supernatant on Th2 cells was inhibited by the CRTH2 antagonist ramatroban. These data suggest that in immunologically activated nasal polyp tissue, PGD(2) produced by mast cells promotes the migration of Th2 cells through a CRTH2 dependent mechanism.

A phase I trial of liposomal doxorubicin, paclitaxel and valspodar (PSC-833), an inhibitor of multidrug resistance

Purpose: The aim of this study was to determine (i) the maximum tolerated dose (MTD) of liposomal doxorubicin (L-DOX) and paclitaxel (DP), (ii) the MTD of DP plus valspodar (DPV) and (iii) pharmacokinetic (PK) interactions of valspodar with L-DOX and paclitaxel.Methods: Twenty-three patients with metastatic cancers received DP, followed 4 weeks later by DPV. Dose levels of DP were (mg/m2 for L-DOX/paclitaxel): 30/135 (n = 7), 30/150 (n = 4), 35/150 (n = 8) and 40/150 (n = 4). Dose levels of DPV were 15/70 (n = 10) and 15/60 (n = 10). Serial, paired PK studies were performed.Results: The MTD of DP was 40/150. For DPV at 15/70, five of 10 patients experienced grade 4 neutropenia. In the next cohort, a reduced dose of 15/60 was well tolerated. Valspodar produced reversible grade 3 ataxia in seven patients, requiring dose reduction from 5 to 4 mg/kg. Paired PK studies indicated no interaction between L-DOX and valspodar, and a 49% increase in the median half-life of paclitaxel. Two partial and one minor remissions were noted.Conclusions: The use of valspodar necessitated dose reductions of DP, with neutropenia being dose limiting. Valspodar PK interactions were observed with paclitaxel but not L-DOX.

Quantitative detection of periodontopathogens by real-time PCR

Specific bacteria are believed to play an important role in chronic periodontitis, yet the significance of their relative numbers in initiation and progress of the disease is still unclear. We report here the development of a sensitive, quantitative PCR technique for enumerating Actinobacillus actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Dialister pneumosintes (Dp) and Micromonas micros (Mm) as well as total eubacteria in subgingival plaque samples from subjects with periodontitis. Quantification was performed with specific 16S rRNA target sequences with double fluorescence labeled probes and serial dilutions of plasmid standard by real-time PCR. This method showed a broad quantification range from 10 2 to 10 8 and accurate sensitivity and specificity. Fifty subgingival plaque samples from periodontitis patients and 33 from periodontally healthy subjects were subsequently examined. Higher levels of total bacteria numbers, Aa, Pg, Dp and Mm were found in samples from periodontitis subjects in comparison to samples from periodontally healthy subjects. Quantitative real-time PCR thus provides a reliable and valuable method for quantification of periodontopathogens in subgingival plaque samples.