bluuebunny/crossref_metadata_2025 huggingface dataset:
Shamba Maisha: A pilot study assessing impacts of a micro-irrigation intervention on the health and economic wellbeing of HIV patients
Authors: Pandit Jay A , Sirotin Nicole , Tittle Robin , Onjolo Elijah , Bukusi Elizabeth A , Cohen Craig R
Published: May 2010

Background

HIV/AIDS negatively impacts poverty alleviation and food security, which reciprocally hinder the rapid scale up and effectiveness of HIV care programs. Nyanza province has the highest HIV prevalence (15.3%), and is the third highest contributor (2.4 million people) to rural poverty in Kenya. Thus, we tested the feasibility of providing a micro-irrigation pump to HIV-positive farmers in order to evaluate its impact on health and economic advancement among HIV-positive patients and their families.

Methods

Thirty HIV-positive patients enrolled in the Family AIDS Care and Education Services (FACES) program in Kisumu, Kenya were provided a micro-financed loan to receive an irrigation pump and farming guidance from KickStart, the developer of the pump. Economic data, CD4 counts, household health and loan repayment history were collected 12 months after the pumps were distributed.

Results

Mean annual family income increased by $1,332 over baseline. CD4 counts did not change significantly. Though income increased, only three (10%) participants had paid off more than a quarter of the loan.

Conclusions

We demonstrated the feasibility of an income-generating micro-irrigation intervention among HIV-positive patients and the collection of health and economic data. While family income improved significantly, loan repayment rates were low- likely complicated by the drought that occurred in Kenya during the intervention period.
Patch Testing in Non-Immediate Drug Eruptions
Authors: Romano Antonino , Viola Marinella , Gaeta Francesco , Rumi Gabriele , Maggioletti Michela
Published: May 2010

The present review addresses the literature regarding the sensitivity and specificity of the various diagnostic methods for evaluating non-immediate (ie, occurring more than 1 hour after drug administration) hypersensitivity reactions associated with β-lactams and other antibiotics, anticonvulsants, heparins, iodinated contrast media, etc. Such reactions include several clinical entities, which range from mild reactions, such as maculopapular rash and delayed-appearing urticaria, to severe ones, such as acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome, and toxic epidermal necrolysis (TEN). Clinical and laboratory studies indicate that a cell-mediated pathogenic mechanism is often involved in maculopapular rashes. However, this mechanism has also been demonstrated in other non-immediate reactions, such as urticarial and/or angioedematous manifestations, TEN, bullous exanthems, and AGEP. Patch tests, together with delayed-reading intradermal tests, lymphocyte transformation tests, and challenges, are useful tools for evaluating non-immediate drug eruptions. Patch tests can be performed with any form of commercial drugs and are safer than intradermal tests. However, patch tests are less sensitive than intradermal tests, and their sensitivity may vary, depending on the vehicle used.
Nature of Regulatory T Cells in the Context of Allergic Disease
Authors: Ozdemir Cevdet , Akdis Mübeccel , Akdis Cezmi A.
Published: May 2010

Allergen-specific immunotherapy (SIT) is the cornerstone of the management of allergic diseases, which targets modification of the immunologic response, along with environmental allergen avoidance and pharmacotherapy. SIT is associated with improved tolerance to allergen challenge, with a decrease in immediate-phase and late-phase allergic inflammation. SIT has the potential to prevent development of new sensitizations and progression of allergic rhinitis to asthma. It has a role in cellular and humoral responses in a modified pattern. The ratio of T helper (Th)1 cytokines to Th2 cytokines is increased following SIT, and functional regulatory T cells are induced. Interleukin-10 production by monocytes, macrophages, and B and T cells is increased, as well as expression of transforming growth factor β. SIT is associated with increases in allergen-specific antibodies in IgA, IgG1, and IgG4 isotypes. These blocking-type immunoglobulins, particularly IgG4, may compete with IgE binding to allergen, decreasing the allergen presentation with the high- and low-affinity receptors for IgE (FcεRI and FcεRII, respectively). Additionally, SIT reduces the number of mast cells and eosinophils in the target tissues and release of mediators from these cells.
Evaluating the Safety of Intranasal Steroids in the Treatment of Allergic Rhinitis
Authors: Sheth Ketan
Published: May 2010

Given that intranasal corticosteroids (INCs) are widely considered first-line therapies for treatment of rhinitis, it is important for the clinician to be comfortable with the side-effect profile and be able to discuss potential safety concerns regarding these therapies. Among the safety concerns with the use of INCs are the potential for growth suppression both short and long term, the potential for hypothalamic-pituitary-adrenal axis suppression, ocular safety, and the use of INCs concomitantly with inhaled corticosteroids in asthma patients. As all clinicians are aware, each patient can have individual responses to both efficacy and safety; however, the data reviewed suggest that the benefits outweigh the potential risks. Understanding the potential concerns and the data behind these concerns should give clinicians the information to be able to discuss this with patients and parents to incorporate appropriate therapy for those with allergic rhinitis
Allergy, Asthma, and Inflammation: Which Inflammatory Cell Type Is More Important?
Authors: Moqbel Redwan , Odemuyiwa Solomon O.
Published: May 2010

A recent review inAllergy, Asthma, and Clinical Immunologysuggested that eosinophils play a minor role, if any, in the inflammatory spectrum of asthma and allergic inflammation. The article that dealt with mast cells suggested that the presence of these important cells within the smooth muscle layer in asthmatic airways renders this cell type primal in asthma and an obvious and important target for therapy. This article proposes that in a complex inflammatory milieu characterizing the complex syndromes we call asthma, no single cell phenotype is responsible for the condition and thus should be a sole target for therapeutic strategies. Our reductionist approach to research in asthma and related conditions has provided us with convincing evidence for multiple roles that immune, inflammatory, and structural cell types can play in complex diseases. The next stage in understanding and ameliorating these complex conditions is to move away from the simplistic notion of one cell type being more important than another. Instead, what is needed is to acquire knowledge of intricate and exquisite biological systems that regulate such conditions in both health and disease involving various cell types, mediators, pharmacologically active products, their multifaceted capacities, and their socio-biological networking.
Assessing and Treating Work-Related Asthma
Authors: Stoughton Tracy , Prematta Michael , Craig Timothy
Published: May 2010

Work-related asthma is asthma that is caused or exacerbated by exposures at work. It is the most common form of occupational lung disease in developed countries. It has important impacts on the health and well-being of the affected individual, as well as consequences for society because of unemployment issues and workers' compensation claims. With ongoing exposure, occupational asthma can result in persistent airway hyperresponsiveness and, possibly, permanent disability for the individual. Thus, it is important for the clinician to be able to diagnose this disorder as quickly and accurately as possible. The evaluation of a patient with work-related asthma can be extensive. It includes obtaining a consistent history, identifying the cause in the workplace, and confirming the diagnosis with objective tests. After a diagnosis has been made, treatment must sometimes go beyond the medications used for nonoccupational asthma and include interventions to minimize or completely remove the individual from exposure to the causal agent if he or she has sensitizer-induced occupational asthma. In addition, once an individual has been identified with occupational asthma, steps should be taken to prevent the development of this disorder in other workers. The purpose of this article is to review the current literature and provide the clinician with a stepwise approach to the diagnosis and management of a patient with work-related asthma.
An emerging recombinant human enterovirus 71 responsible for the 2008 outbreak of Hand Foot and Mouth Disease in Fuyang city of China
Authors: Zhang Yan , Zhu Zhen , Yang Weizhong , Ren Jun , Tan Xiaojuan , Wang Yu , Mao Naiying , Xu Songtao , Zhu Shuangli , Cui Aili , Zhang Yong , Yan Dongmei , Li Qun , Dong Xiaoping , Zhang Jing , Zhao Yueping , Wan Junfeng , Feng Zijian , Sun Junling , Wang Shiwen , Li Dexin , Xu Wenbo
Published: May 2010

Hand, foot and mouth disease (HFMD), a common contagious disease that usually affects children, is normally mild but can have life-threatening manifestations. It can be caused by enteroviruses, particularly Coxsackieviruses and human enterovirus 71 (HEV71) with highly variable clinical manifestations. In the spring of 2008, a large, unprecedented HFMD outbreak in Fuyang city of Anhui province in the central part of southeastern China resulted in a high aggregation of fatal cases. In this study, epidemiologic and clinical investigations, laboratory testing, and genetic analyses were performed to identify the causal pathogen of the outbreak. Of the 6,049 cases reported between 1 March and 9 May of 2008, 3023 (50%) were hospitalized, 353 (5.8%) were severe and 22 (0.36%) were fatal. HEV71 was confirmed as the etiological pathogen of the outbreak. Phylogenetic analyses of entire VP1 capsid protein sequence of 45 Fuyang HEV71 isolates showed that they belong to C4a cluster of the C4 subgenotype. In addition, genetic recombinations were found in the 3D region (RNA-dependent RNA polymerase, a major component of the viral replication complex of the genome) between the Fuyang HEV71 strain and Coxsackievirus A16 (CV-A16), resulting in a recombination virus. In conclusion, an emerging recombinant HEV71 was responsible for the HFMD outbreak in Fuyang City of China, 2008.
Enhancement of anti-DIII antibodies by the C3d derivative P28 results in lower viral titers and augments protection in mice
Authors: Dunn Matthew D , Rossi Shannan L , Carter Donald M , Vogt Matthew R , Mehlhop Erin , Diamond Michael S , Ross Ted M
Published: May 2010

Antibodies generated against West Nile virus (WNV) during infection are essential for controlling dissemination. Recent studies have demonstrated that epitopes in all three domains of the flavivirus envelope protein (E) are targets for neutralizing antibodies, with determinants in domain III (DIII) eliciting antibodies with strong inhibitory properties. In order to increase the magnitude and quality of the antibody response against the WNV E protein, DNA vaccines with derivatives of the WNV E gene (full length E, truncated E, or DIII region, some in the context of the pre-membrane [prM] gene) were conjugated to the molecular adjuvant P28. The P28 region of the complement protein C3d is the minimum CR2-binding domain necessary for the adjuvant activity of C3d. Delivery of DNA-based vaccines by gene gun and intramuscular routes stimulated production of IgG antibodies against the WNV DIII region of the E protein. With the exception of the vaccine expressing prM/E given intramuscularly, only mice that received DNA vaccines by gene gun produced protective neutralizing antibody titers (FRNT80 titer >1/40). Correspondingly, mice vaccinated by the gene gun route were protected to a greater level from lethal WNV challenge. In general, mice vaccinated with P28-adjuvated vaccines produced higher IgG titers than mice vaccinated with non-adjuvanted vaccines.
Analysis of clinical and dosimetric factors associated with severe acute radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with concurrent chemotherapy and intensity-modulated radiotherapy
Authors: Shi Anhui , Zhu Guangying , Wu Hao , Yu Rong , Li Fuhai , Xu Bo
Published: May 2010

Background

To evaluate the association between the clinical, dosimetric factors and severe acute radiation pneumonitis (SARP) in patients with locally advanced non-small cell lung cancer (LANSCLC) treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT).

Methods

We analyzed 94 LANSCLC patients treated with concurrent chemotherapy and IMRT between May 2005 and September 2006. SARP was defined as greater than or equal 3 side effects and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

The clinical and dosimetric factors were analyzed. Univariate and multivariate logistic regression analyses were performed to evaluate the relationship between clinical, dosimetric factors and SARP.

Results

Median follow-up was 10.5 months (range 6.5-24). Of 94 patients, 11 (11.7%) developed SARP. Univariate analyses showed that the normal tissue complication probability (NTCP), mean lung dose (MLD), relative volumes of lung receiving more than a threshold dose of 5-60 Gy at increments of 5 Gy (V5-V60), chronic obstructive pulmonary disease (COPD) and Forced Expiratory Volume in the first second (FEV1) were associated with SARP (p < 0.05). In multivariate analysis, NTCP value (p = 0.001) and V10 (p = 0.015) were the most significant factors associated with SARP. The incidences of SARP in the group with NTCP > 4.2% and NTCP ≤4.2% were 43.5% and 1.4%, respectively (p < 0.01). The incidences of SARP in the group with V10 ≤50% and V10 >50% were 5.7% and 29.2%, respectively (p < 0.01).

Conclusions

NTCP value and V10 are the useful indicators for predicting SARP in NSCLC patients treated with concurrent chemotherapy and IMRT.
Enhancement of cisplatin sensitivity in lewis lung carcinoma by liposome-mediated delivery of a survivin mutant
Authors: Yu Dan-Dan , Wang Chun-Ting , Shi Hua-Shan , Li Zhi-Yong , Pan Li , Yuan Qing-Zhong , Leng Fei , Wen Yuan , Chen Xiang , Wei Yu-Quan
Published: May 2010

Background

A high concentration of cisplatin (CDDP) induces apoptosis in many tumor cell lines. CDDP has been administered by infusion to avoid severe toxicity. Recently, it has been reported that changes in survivin expression or function may lead to tumor sensitization to chemical and physical agents. The aim of this study was to determine whether a dominant-negative mouse survivin mutant could enhance the anti-tumor activity of CDDP.

Methods

A plasmid encoding the phosphorylation-defective dominant-negative mouse survivin threonine 34→alanine mutant (survivin T34A) complexed to a DOTAP-chol liposome (Lip-mS) was administered with or without CDDP in Lewis Lung Carcinoma (LLC) cells and in mice bearing LLC tumors, and the effects on apoptosis, tumor growth and angiogenesis were assessed. Data were analyzed using one-way analysis of variance(ANOVA), and a value of P < 0.05 was considered to be statistically significant.

Results

LLC cells treated with a combination of Lip-mS and CDDP displayed increased apoptosis compared with those treated with Lip-mS or CDDP alone. In mice bearing LLC tumors and treated with intravenous injections of Lip-mS and/or CDDP, combination treatment significantly reduced the mean tumor volume compared with either treatment alone. Moreover, the antitumor effect of Lip-mS combined with CDDP was greater than their anticipated additive effects.

Conclusion

These data suggest that the dominant-negative survivin mutant, survivin T34A, sensitized LLC cells to chemotherapy of CDDP. The synergistic antitumor activity of the combination treatment may in part result from an increase in the apoptosis of tumor cells, inhibition of tumor angiogenesis and induction of a tumor-protective immune response.
Comparison of body mass index and waist circumference as predictors of cardiometabolic health in a population of young Canadian adults
Authors: Brenner Darren R , Tepylo Kasia , Eny Karen M , Cahill Leah E , El-Sohemy Ahmed
Published: May 2010

Background

This study aimed to investigate whether waist circumference (WC) or body mass index (BMI) is a better predictor of blood lipid concentrations among young men and women from different ethnocultural groups.

Methods

Participants were 1181 healthy men (n = 358) and women (n = 823) aged 20-29 years taken from the cross-sectional Toronto Nutrigenomics and Health Study. Analyses were conducted separately for men and women, and for Caucasian and East Asian ethnocultural groups. Serum triglycerides (TG) and total to HDL cholesterol ratio (TC:HDL cholesterol) were used as outcomes. Associations between the adiposity and blood lipid measures were examined using partial correlations and odds ratios derived from logistic regression models.

Results

WC had a stronger association with serum lipid concentrations than BMI. WC was significantly related to TG and TC:HDL cholesterol after adjusting for BMI and covariates among men and women (P ≤ 0.01). However, after adjusting for WC and covariates, BMI was not significantly associated with the two serum lipid measures. WC was a better predictor of TG and TC:HDL among all sex and ethnocultural subgroups except among East Asian women where little difference between the two measures was observed.

Conclusions

WC is a stronger predictor of cardiometabolic health when compared with BMI among young adults, especially among men.
Cell culture and passaging alters gene expression pattern and proliferation rate in rheumatoid arthritis synovial fibroblasts
Authors: Neumann Elena , Riepl Birgit , Knedla Anette , Lefèvre Stephanie , Tarner Ingo H , Grifka Joachim , Steinmeyer Jurgen , Schölmerich Jurgen , Gay Steffen , Müller-Ladner Ulf
Published: May 2010

Introduction

Rheumatoid arthritis synovial fibroblasts (RASF) are key players in synovial pathophysiology and are therefore examined extensively in various experimental approaches. We evaluated, whether passaging during culture and freezing has effects on gene expression and cell proliferation.

Methods

RASF were passaged for up to 8 passages. RNA was isolated after each passage and cDNA arrays were performed to evaluate the RNA expression pattern during passaging. In addition, doubling time of the cells was also measured.

Results

From passages 2-4, mRNA expression did not change significantly. Gene expression in RASF started to change in passages 5-6 with 7-10% differentially expressed genes. After passages 7-8, more than 10% of the genes were differentially expressed. The doubling rate was constant for up to 5 passages and decreased after passages 6-8. After freezing, gene expression of the second passage is comparable to gene expression prior to freezing.

Conclusions

The results of this study show, that experiments, which examine gene expression of RASF and shall reflect or imitate an in vivo situation, should be limited to early culture passages to avoid cell culture effects. It is not necessary to stop culturing SF after a few passages, but to keep the problems of cell culture in mind to avoid false positive results. Especially, when large-scale screening methods on mRNA level are used. Of note, freezing does not affect gene expression substantially.
Provision of preventive health care in systemic lupus erythematosus: data from a large observational cohort study
Authors: Yazdany Jinoos , Tonner Chris , Trupin Laura , Panopalis Pantelis , Gillis Joann Z , Hersh Aimee O , Julian Laura J , Katz Patricia P , Criswell Lindsey A , Yelin Edward H
Published: May 2010

Introduction

Cancer and infections are leading causes of mortality in systemic lupus erythematosus (SLE) after diseases of the circulatory system, and therefore preventing these complications is important. In this study, we examined two categories of preventive services in SLE: cancer surveillance (cervical, breast, and colon) and immunizations (influenza and pneumococcal). We compared the receipt of these services in SLE to the general population, and identified subgroups of patients who were less likely to receive these services.

Methods

We compared preventive services reported by insured women with SLE enrolled in the University of California, San Francisco Lupus Outcomes Study (n = 685) to two representative samples derived from a statewide health interview survey, a general population sample (n = 18,013) and a sample with non-rheumatic chronic conditions (n = 4,515). In addition, using data from the cohort in both men and women (n = 742), we applied multivariate regression analyses to determine whether characteristics of individuals (for example, sociodemographic and disease factors), health systems (for example, number of visits, involvement of generalists or rheumatologists in care, type of health insurance) or neighborhoods (neighborhood poverty) influenced the receipt of services.

Results

The receipt of preventive care in SLE was similar to both comparison samples. For cancer surveillance, 70% of eligible respondents reported receipt of cervical cancer screening and mammography, and 62% reported colon cancer screening. For immunizations, 59% of eligible respondents reported influenza immunization, and 60% reported pneumococcal immunization. In multivariate regression analyses, several factors were associated with a lower likelihood of receiving preventive services, including younger age and lower educational attainment. We did not observe any effects by neighborhood poverty. A higher number of physician visits and involvement of generalist providers in care was associated with a higher likelihood of receiving most services.

Conclusions

Although receipt of cancer screening procedures and immunizations in our cohort was comparable to the general population, we observed significant variability by sociodemographic factors such as age and educational attainment. Further research is needed to identify the physician, patient or health system factors contributing to this observed variation in order to develop effective quality improvement interventions.
Inhibition of phosphatidylcholine-specific phospholipase C downregulates HER2 overexpression on plasma membrane of breast cancer cells
Authors: Paris Luisa , Cecchetti Serena , Spadaro Francesca , Abalsamo Laura , Lugini Luana , Pisanu Maria Elena , Iorio Egidio , Natali Pier Giorgio , Ramoni Carlo , Podo Franca
Published: May 2010

Introduction

Overexpression on plasma membrane of human epidermal growth factor receptor 2 (HER2) is reported in 25% to 30% of breast cancers. Heterodimer formation with cognate members of the epidermal growth factor receptor (EGFR) family, such as HER3 and EGFR, activates abnormal cell-signalling cascades responsible for tumorigenesis and further transcriptional HER2 gene upregulation. Targeting the molecular mechanisms controlling HER2 overexpression and recycling may effectively deactivate this feedback-amplification loop. We recently showed that inactivation of phosphatidylcholine-specific phospholipase C (PC-PLC) may exert a pivotal role in selectively modulating the expression on the membrane of specific receptors or proteins relevant to cell function. In the present study, we investigated the capability of PC-PLC inhibition to target the molecular mechanisms controlling HER2 overexpression on the membrane of breast cancer cells by altering the rates of its endocytosis and lysosomal degradation.

Methods

Localization on the membrane and interaction of PC-PLC with HER2, EGFR, and HER3 were investigated on HER2-overexpressing and HER2-low breast cancer cell lines, by using confocal laser scanning microscopy, flow cytometry, cell-surface biotinylation, isolation of lipid rafts, and immunoprecipitation experiments. The effects of the PC-PLC inhibitor tricyclodecan-9-yl-potassium xanthate (D609) on HER2 expression on the membrane and on the levels of overall HER2, HER2-HER3, and HER2-EGFR contents were monitored in the HER2-overexpressing SKBr3 cells, after either transient or continuous receptor engagement with anti-HER2 monoclonal antibodies, including trastuzumab. Changes of HER2 expression and cell proliferation were examined in SKBr3, BT-474, and MDA-MB-453 cells continuously exposed to D609 alone or combined with trastuzumab.

Results

PC-PLC selectively accumulates on the plasma membrane of HER2-overexpressing cells, where it colocalizes and associates with HER2 in raft domains. PC-PLC inhibition resulted in enhanced HER2 internalization and lysosomal degradation, inducing downmodulation of HER2 expression on the membrane. Moreover, PC-PLC inhibition resulted in strong retardation of HER2 reexpression on the membrane and a decrease in the overall cellular contents of HER2, HER2-HER3, and HER2-EGFR heterodimers. The PC-PLC inhibitor also induced antiproliferative effects, especially in trastuzumab-resistant cells.

Conclusions

The results pointed to PC-PLC inhibition as a potential means to counteract the tumorigenic effects of HER2 amplification and complement the effectiveness of current HER2-targeting therapies.
Urinary cystatin C is diagnostic of acute kidney injury and sepsis, and predicts mortality in the intensive care unit
Authors: Nejat Maryam , Pickering John W , Walker Robert J , Westhuyzen Justin , Shaw Geoffrey M , Frampton Christopher M , Endre Zoltán H
Published: May 2010

Introduction

To evaluate the utility of urinary cystatin C (uCysC) as a diagnostic marker of acute kidney injury (AKI) and sepsis, and predictor of mortality in critically ill patients.

Methods

This was a two-center, prospective AKI observational study and post hoc sepsis subgroup analysis of 444 general intensive care unit (ICU) patients. uCysC and plasma creatinine were measured at entry to the ICU. AKI was defined as a 50% or 0.3-mg/dL increase in plasma creatinine above baseline. Sepsis was defined clinically. Mortality data were collected up to 30 days. The diagnostic and predictive performances of uCysC were assessed from the area under the receiver operator characteristic curve (AUC) and the odds ratio (OR). Multivariate logistic regression was used to adjust for covariates.

Results

Eighty-one (18%) patients had sepsis, 198 (45%) had AKI, and 64 (14%) died within 30 days. AUCs for diagnosis by using uCysC were as follows: sepsis, 0.80, (95% confidence interval (CI), 0.74 to 0.87); AKI, 0.70 (CI, 0.64 to 0.75); and death within 30 days, 0.64 (CI, 0.56 to 0.72). After adjustment for covariates, uCysC remained independently associated with sepsis, AKI, and mortality with odds ratios (CI) of 3.43 (2.46 to 4.78), 1.49 (1.14 to 1.95), and 1.60 (1.16 to 2.21), respectively. Concentrations of uCysC were significantly higher in the presence of sepsis (P < 0.0001) or AKI (P < 0.0001). No interaction was found between sepsis and AKI on the uCysC concentrations (P = 0.53).

Conclusions

Urinary cystatin C was independently associated with AKI, sepsis, and death within 30 days.

Trial registration

Australian New Zealand Clinical Trials Registry ACTRN012606000032550.
Beneficial effects of loxapine on agitation and breathing patterns during weaning from mechanical ventilation
Authors: Sztrymf Benjamin , Chevrel Guillaume , Bertrand Fabrice , Margetis Dimitri , Hurel Dominique , Ricard Jean-Damien , Dreyfuss Didier
Published: May 2010

Introduction

Interruption of sedation during weaning from mechanical ventilation often leads to patient agitation because of withdrawal syndrome. We tested the short-term efficacy and tolerance of loxapine in this situation.

Methods

Nineteen mechanically ventilated patients with marked agitation after sedation withdrawal were included. Three agitation scales, the Richmond Agitation Sedation Scale (RASS), the Motor Activity Assessment Scale (MAAS), and the Ramsay and physiological variables (respiratory rate, airway occlusion pressure during the first 0.1 second of inspiration (P0.1), heart rate and systolic arterial blood pressure) were recorded before and after loxapine administration.

Results

Loxapine dramatically improved all agitation scores (RASS and MASS decreased from 2 ± 0 to -1.1 ± 2.3, and 5.4 ± 0.5 to 2.7 ± 1.6, respectively; Ramsay increased from 1.0 ± 0 to 3.5 ± 1.5, 60 minutes after loxapine administration, P < 0.05 for all scores) as well as P0.1 (6 ± 4.2 to 1.8 ± 1.8 cm H2O; P < 0.05) and respiratory rate (from 31.2 ± 7.2 to 23.4 ± 7.8; P < 0.05) without hemodynamic adverse events. No side effects occurred. Sixteen (84%) patients were successfully managed with loxapine, sedation was resumed in two others, and one patient self-extubated without having to be reintubated.

Conclusions

Loxapine was safe and effective in treating agitation in a small group of mechanically ventilated patients and improved respiratory physiologic parameters, enabling the weaning process to be pursued. A multicenter trial is under way to confirm these promising results.
Nucleosome rotational setting is associated with transcriptional regulation in promoters of tissue-specific human genes
Authors: Hebert Charles , Roest Crollius Hugues
Published: May 2010

Background

The position of a nucleosome, both translational along the DNA molecule and rotational between the histone core and the DNA, is controlled by many factors, including the regular occurrence of specific dinucleotides with a period of approximately 10 bp, important for the rotational setting of the DNA around the histone octamer.

Results

We show that such a 10 bp periodic signal of purine-purine dinucleotides occurs in phase with the transcription start site (TSS) of human genes and is centered on the position of the first (+1) nucleosome downstream of the TSS. These data support a direct link between transcription and the rotational setting of the nucleosome. The periodic signal is most prevalent in genes that contain CpG islands that are expressed at low levels in a tissue-specific manner and are involved in the control of transcription.

Conclusions

These results, together with several lines of evidence from the recent literature, support a new model whereby the +1 nucleosome could be more efficiently disassembled from gene promoters by H3K56 acetylation marks if the periodic signal specifies an optimal rotational setting.
Claudin-2, a component of the tight junction, forms a paracellular water channel
Authors: Rosenthal Rita , Milatz Susanne , Krug Susanne M. , Oelrich Beibei , Schulzke Jörg-Dieter , Amasheh Salah , Günzel Dorothee , Fromm Michael
Published: May 2010

Whether or not significant amounts of water pass the tight junction (TJ) of leaky epithelia is still unresolved, because it is difficult to separate transcellular water flux from TJ-controlled paracellular water flux. Using an approach without differentiating technically between the transcellular and paracellular route, we measured transepithelial water flux with and without selective molecular perturbation of the TJ to unequivocally attribute changes to the paracellular pathway. To this end, MDCK C7 cells were stably transfected with either claudin-2 or claudin-10b, two paracellular cation-channel-forming TJ proteins that are not endogenously expressed in this cell line. Claudin-2 is typical of leaky, water-transporting epithelia, such as the kidney proximal tubule, whereas claudin-10b is present in numerous epithelia, including water-impermeable segments of the loop of Henle. Neither transfection altered the expression of endogenous claudins or aquaporins. Water flux was induced by an osmotic gradient, a Na+ gradient or both. Under all conditions, water flux in claudin-2-transfected cells was elevated compared with vector controls, indicating claudin-2-mediated paracellular water permeability. Na+-driven water transport in the absence of an osmotic gradient indicates a single-file mechanism. By contrast, claudin-10b transfection did not alter water flux. We conclude that claudin-2, but not claudin-10b, forms a paracellular water channel and thus mediates paracellular water transport in leaky epithelia.
ADF/cofilin-driven actin dynamics in early events ofLeishmaniacell division
Authors: Tammana T. V. Satish , Sahasrabuddhe Amogh A. , Bajpai Virendra K. , Gupta Chhitar M.
Published: May 2010

ADF/cofilin is an actin-dynamics-regulating protein that is required for several actin-based cellular processes such as cell motility and cytokinesis. A homologue of this protein has recently been identified in the protozoan parasite Leishmania, which has been shown to be essentially required in flagellum assembly and cell motility. However, the role of this protein in cytokinesis remains largely unknown. We show here that deletion of the gene encoding ADF/cofilin in these organisms results in several aberrations in the process of cell division. These aberrations include delay in basal body and kinetoplast separation, cleavage furrow progression and flagellar pocket division. In addition to these changes, the intracellular trafficking and actin dynamics are also adversely affected. All these abnormalities are, however, reversed by episomal complementation. Together, these results indicate that actin dynamics regulates early events in Leishmania cell division.
The Gender Gap in Secondary School Mathematics at High Achievement Levels: Evidence from the American Mathematics Competitions
Authors: Ellison Glenn , Swanson Ashley
Published: May 2010

This paper uses a new data source, American Mathematics Competitions, to examine the gender gap among high school students at very high achievement levels. The data bring out several new facts. There is a large gender gap that widens dramatically at percentiles above those that can be examined using standard data sources. An analysis of unobserved heterogeneity indicates that there is only moderate variation in the gender gap across schools. The highest achieving girls in the U.S. are concentrated in a very small set of elite schools, suggesting that almost all girls with the ability to reach high math achievement levels are not doing so.
But Economics Is Not an Experimental Science
Authors: Sims Christopher A
Published: May 2010

The fact is, economics is not an experimental science and cannot be. “Natural” experiments and “quasi” experiments are not in fact experiments. They are rhetorical devices that are often invoked to avoid having to confront real econometric difficulties. Natural, quasi-, and computational experiments, as well as regression discontinuity design, can all, when well applied, be useful, but none are panaceas. The essay by Angrist and Pischke, in its enthusiasm for some real accomplishments in certain subfields of economics, makes overbroad claims for its favored methodologies. What the essay says about macroeconomics is mainly nonsense. Consequently, I devote the central part of my comment to describing the main developments that have helped take some of the con out of macroeconomics. Recent enthusiasm for single-equation, linear, instrumental variables approaches in applied microeconomics has led many in these fields to avoid undertaking research that would require them to think formally and carefully about the central issues of nonexperimental inference—what I see and many see as the core of econometrics. Providing empirically grounded policy advice necessarily involves confronting these difficult central issues.
The influence of rape myth acceptance, sexual attitudes, and belief in a just world on attributions of responsibility in a date rape scenario
Authors: Hammond Elizabeth M. , Berry Melissa A. , Rodriguez Dario N.
Published: May 2010

Purpose. The purpose of this study was to examine the influence of rape myth acceptance, belief in a just world, and sexual attitudes on attributions of responsibility in a date rape scenario. We predicted that people higher in rape myth acceptance and those who more strongly believed in a just world, as well as those who held more conservative sexual attitudes, would attribute greater blame to the accuser than to the accused.

Methods. One hundred seventy‐two undergraduates from a medium‐sized, Catholic university in the USA read a hypothetical date rape scenario and completed the Rape Myth Acceptance Scale, the Just World Scale, the Sexual Attitudes Scale, and a Judgment Questionnaire constructed for the current study.

Results. Rape myth acceptance mediated the relationship between gender and judgments of responsibility for the accused and the accuser. Men were more likely to endorse rape myths and, consequently, assign less responsibility to the accused and more responsibility to the accuser than women.

Conclusions. Pre‐existing beliefs regarding the nature of rape and the circumstances surrounding it may bias attributions of responsibility in date rape cases. There may be utility in addressing whether jurors hold such beliefs prior to the start of a trial.
Illusions of transcendence: Laurent Chevallier's Circus Baobab and the volatile charms of Guinean youth performance arts
Authors: Straker Jay
Published: May 2010

Shot in a distinctively lyrical, experimental style, Laurent Chevallier's documentary Circus Baobab (2001) chronicled the pioneering tour of le premier cirque acrobatique arien d'Afrique across the Republic of Guinea. The film evinced a reverence for Guinea's cultural patrimonies,
the sociological and environmental attributes of its interior regions and the spellbinding dance and acrobatic talents of the local youths who were the stars of the travelling spectacle. Despite these romantic elements, Chevallier's venture proved in significant respects a complicated reflection
of colonial and postcolonial cultural politics and conflicts. This article explores some of the complex dynamics that shaped Chevallier's multifaceted project, as well as the disjunctive meanings and values ascribed to it by metropolitan and Guinean spectators. In its emphasis on the political
volatility of Guinean youth performance arts over time, it hopes to expand the domains of interest and interpretive frameworks shaping cultural studies of Francophone West Africa.
Baroque practices in postcolonial African literature and theory: from Achille Mbembe's On the Postcolony
Authors: Joslin Isaac V
Published: May 2010

This article aims to elucidate a baroque aesthetic practice in the political and literary spheres of postcolonial Francophone Africa, which extends beyond the binary oppositions of power and powerlessness in a relational dynamic of subversive complicity. The baroque character and correlative
baroque practices in the politics of the Postcolony identified by Achille Mbembe are depicted, embodied and transmitted in the literary production of postcolonial African writers. This baroque reorientation opens new ways of reading stylistic innovations and political encoding in a framework
that blurs the line between reality and representation, which is exemplified in the novelistic practice of Henri Lopes and Sony Labou Tansi, among others. Accordingly, the baroque as a theoretical approach to reading postcolonial Francophone literature and its socio-political context engenders
an understanding of how art and literature can represent and embody, in a certain sense, different forms of what douard Glissant depicts as baroque: being-in-the-world.
SKML-Quality Mark for point-of-care test (POCT) glucose meters and glucose meters for home-use
Authors: Jansen Rob T.P. , Slingerland Robbert J.
Published: May 2010

Background: Point-of-care glucose meters are used increasingly in semi- and non-professional context. The quality of glucose measurements depends on the quality of the equipment, the quality of use, and the pre-analytical conditions. In this article, a External Quality Assessment Scheme (SKML)-Quality Mark for point-of-care test (POCT) and self-test glucose meters is proposed, assessing analytical quality and technical quality. The analytical requirements are based on the biological variation concept, and a system to assess meters for the SKML-Quality Mark is described. Using the proposed system as an example, 14 meters were tested.

Methods: The analytical quality of the POCT and self-test equipment was assessed for plasma calibrated glucose values by comparison with a trueness verified method traceable to the IFCC reference method in an accredited clinical laboratory. The concept is based on the biological variation system. The SKML-Quality Mark comprises the following criteria for blood glucose equipment: 1) Fulfilment of compliance with ISO 15197 and/or TNO guideline criterion; 2) Fulfilment of the total allowable error (TAE) criterion; 3) Fulfilment of the total allowable linearity bias criterion; 4) Fulfilment of the total allowable interfering substances bias criterion; and 5) Fulfilment of the haematocrit criterion.

Results: The proposed SKML-Quality Mark system was tested on 14 commercial home-use meters. The TAE criterion is violated by two meters. The main reason for the violation is bias. For the majority of meters, the Passing and Bablok regression confidence interval does not include the intercept of 0.0 and slope of 1.0. In addition, Syx indicates dispersion around the line or non-linearity. The bias and total error at three different concentrations were investigated as part of the quality mark, resulting in disapproval of the Dicomed Sensocard Plus meter. The bias was significant for the Wellion Linus. With respect to interfering substances, bias of the same magnitude and sign as the bias without additive was seen for all meters for acetaminophen, indicating no additional interference. For ascorbic acid, an additional bias was seen for several meters. However, significant bias was demonstrated for the Sensocard Plus and Glucocard X-meter.

Conclusions: The biological variation concept offers a scientific basis for assessment of acceptable deviation. The concept is extended in the SKML-Quality Mark correcting for the limited number of measurements that can be performed while assessing home-use or POCT meters. The results show that three out of 14 meters fail the proposed quality mark.

Clin Chem Lab Med 2010;48:1021–7.
Human Medial Temporal Lobe Damage Can Disrupt the Perception of Single Objects
Authors: Lee Andy C. H. , Rudebeck Sarah R.
Published: May 2010

The idea that the medial temporal lobe (MTL), traditionally viewed as an exclusive memory system, may also subserve higher-order perception has been debated fiercely. To support this suggestion, monkey and human lesion studies have demonstrated that perirhinal cortex damage impairs complex object discrimination. The interpretation of these findings has, however, been disputed because these impairments may reflect a primary deficit in MTL-mediated working memory processes or, in the case of human patients, undetected damage to visual processing regions beyond the MTL. To address these issues, this study investigated object perception in two human amnesic patients who were chosen on the basis of their lesion locations and suitability for detailed neuroimaging investigation. A neuropsychological task with minimal working memory demands was administered in which participants assessed the structural coherency of single novel objects. Critically, only the patient with perirhinal atrophy was impaired. Moreover, volumetric and functional neuroimaging data demonstrated that this deficit cannot be attributed to the dysfunction of visual cortical areas. Additional analyses of eye-movement patterns during the perceptual task revealed an inability of this patient to detect structural incoherency consistently. This study uses a combination of techniques to provide strong evidence that the perirhinal cortex subserves perception and suggests that the MTL perceptual-mnemonic debate cannot be dismissed on the basis of anatomy or a working memory impairment.
Enteric Glia Are Targets of the Sympathetic Innervation of the Myenteric Plexus in the Guinea Pig Distal Colon
Authors: Gulbransen Brian D. , Bains Jaideep S. , Sharkey Keith A.
Published: May 2010

Astrocytes respond to synaptic activity in the CNS. Astrocytic responses are synapse specific and precisely regulate synaptic activity. Glia in the peripheral nervous system also respond to neuronal activity, but it is unknown whether glial responses are synapse specific. We addressed this issue by examining the activation of enteric glia by distinct neuronal subpopulations in the enteric nervous system. Enteric glia are unique peripheral glia that surround enteric neurons and respond to neuronally released ATP with increases in intracellular calcium ([Ca2+]i). Autonomic control of colonic function is mediated by intrinsic (enteric) and extrinsic (sympathetic, parasympathetic, primary afferent) neural pathways. Here we test the hypothesis that a defined population of neurons activates enteric glia using a variety of techniques to ablate or stimulate components of the autonomic innervation of the colon. Our findings demonstrate that, in the male guinea pig colon, activation of intrinsic neurons does not stimulate glial [Ca2+]iresponses and fast enteric neurotransmission is not necessary to initiate glial responses. However, ablating extrinsic innervation significantly reduces glial responses to neuronal activation. Activation of primary afferent fibers does not activate glial [Ca2+]iresponses. Selectively ablating sympathetic fibers reduces glial activation to a similar extent as total extrinsic denervation. Neuronal activation of glia follows the same frequency dependence as sympathetic neurotransmitter release, but the only sympathetic neurotransmitter that activates glial [Ca2+]iresponses is ATP, suggesting that sympathetic fibers release ATP to activate enteric glia. Therefore, enteric glia discern activity in adjacent synaptic pathways and selectively respond to sympathetic activation.
Interactive Effects of Stress and Aging on Structural Plasticity in the Prefrontal Cortex
Authors: Bloss Erik B. , Janssen William G. , McEwen Bruce S. , Morrison John H.
Published: May 2010

Neuronal networks in the prefrontal cortex mediate the highest levels of cognitive processing and decision making, and the capacity to perform these functions is among the cognitive features most vulnerable to aging. Despite much research, the neurobiological basis of age-related compromised prefrontal function remains elusive. Many investigators have hypothesized that exposure to stress may accelerate cognitive aging, though few studies have directly tested this hypothesis and even fewer have investigated a neuronal basis for such effects. It is known that in young animals, stress causes morphological remodeling of prefrontal pyramidal neurons that is reversible. The present studies sought to determine whether age influences the reversibility of stress-induced morphological plasticity in rat prefrontal neurons. We hypothesized that neocortical structural resilience is compromised in normal aging. To directly test this hypothesis we used a well characterized chronic restraint stress paradigm, with an additional group allowed to recover from the stress paradigm, in 3-, 12-, and 20-month-old male rats. In young animals, stress induced reductions of apical dendritic length and branch number, which were reversed with recovery; in contrast, middle-aged and aged rats failed to show reversible morphological remodeling when subjected to the same stress and recovery paradigm. The data presented here provide evidence that aging is accompanied by selective impairments in long-term neocortical morphological plasticity.