Many commentators have contrasted the way that sociability is theorized in the writings of Mary Astell and Damaris Masham, emphasizing the extent to which Masham is more interested in embodied, worldly existence. I argue, by contrast, that Astell's own interest in imagining a constitutively relational individual emerges once we pay attention to her use of religious texts and tropes. To explore the relevance of Astell's Christianity, I emphasize both how Astell's Christianity shapes her view of the individual's relation to society and how Masham's contrasting views can be analyzed through the lens of her charge that Astell is an “enthusiast.” In late seventeenth-century England, “enthusiasm” was a term of abuse that, commentators have recently argued, could function polemically to dismiss those deemed either excessively social or antisocial. By accusing Astell of enthusiasm, I claim, Masham seeks to marginalize the relational self that Astell imagines and to promote a more instrumental view of social ties. I suggest some aspects of Astell's thought that may have struck contemporaries as “enthusiastic” and contrast her vision of the self with Masham's more hedonistic subject. I conclude that, although each woman differently configures the relation between self and society, they share a desire to imagine autonomy within a relational framework.
Monday, April 30, 2012
Chronic rhinosinusitis symptoms and computed tomography staging: improved correlation by incorporating radiographic density
Abstract
Background:
Traditional methods for staging of chronic rhinosinusitis (CRS) by computed tomography (CT) have not proven to be predictive of subjective reports of patients' symptoms. An objective measure of CRS severity that correlates well with patients' symptoms, particularly if available from CT data, would be a valuable tool in assessment of disease status and outcomes after surgery.
Methods:
Retrospective chart review of CRS patients with symptom data from the Rhinosinusitis Symptom Inventory (RSI) and objective data from a sinus CT scan. CRS disease severity on CT imaging was measured according to the traditional Lund-Mackay scoring, as well as by raw measures of the densities of sinus opacities (in Hounsfield units [HU]) and density-weighted Lund-Mackay scoring. These data were related to symptom severity scores using a multivariate regression model.
Results:
There was no significant correlation between either raw density values of sinus opacities or weighted Lund-Mackay scores with facial or total symptom scores. Oropharyngeal symptoms scores were negatively correlated with the sum of “average HU” values (p = 0.036, β = −1.120) but were positively correlated with the sum of “maximum HU” values (p = 0.047, β = 1.221). There was a significant negative correlation between the systemic symptoms score and mean of “average HU” values (p = 0.010, β = −0.272). Finally, there was a positive correlation between “maximum HU” value-weighted Lund-Mackay score with nasal symptom scores (p = 0.016, β = 0.241), systemic symptom scores (p = 0.008, β = 0.605), and total symptom scores (p = 0.078, β = 0.179).
Conclusion:
Incorporation of radiographic characteristics of sinus opacification with Lund-Mackay scores offers greater predictive power of patients' subjective symptom severity. © 2012 ARS-AAOA, LLC.
Toward a Postcolonial, Posthumanist Feminist Theory: Centralizing Race and Culture in Feminist Work on Nonhuman Animals
Posthumanist feminist theory has been instrumental in demonstrating the salience of gender and sexism in structuring human–animal relationships and in revealing the connections between the oppression of women and of nonhuman animals. Despite the richness of feminist posthumanist theorizations it has been suggested that their influence in contemporary animal ethics has been muted. This marginalization of feminist work—here, in its posthumanist version—is a systemic issue within theory and needs to be remedied. At the same time, the limits of posthumanist feminist theory must also be addressed. Although posthumanist feminist theory has generated a sophisticated body of work analyzing how gendered and sexist discourses and practices subordinate women and animals alike, its imprint in producing intersectional analyses of animal issues is considerably weaker. This leaves theorists vulnerable to charges of essentialism, ethnocentrism, and elitism despite best intentions to avoid such effects and despite commitments to uproot all forms of oppression. Gender-focused accounts also preclude understanding of the importance of race and culture in structuring species-based oppression. To counter these undesirable pragmatic and conceptual developments, posthumanist feminist theory needs to engender feminist accounts that centralize the structural axes of race and culture.
The Hospital's Role in Improving Survival of Patients With Out-of-Hospital Cardiac Arrest
Abstract
Out-of-hospital cardiac arrest (OHCA) is a major public health problem. Unfortunately, in spite of recurring updated guidelines, survival of patients with OHCA had been unchanged for decades. Recently, new approaches to patients with OHCA during the community and prehospital phases of therapy for cardiac arrest have resulted in a dramatic improvement in survival. Further improvement in survival has resulted from hospitals designated as Cardiac Receiving Centers. These centers are committed to the treatment of post-cardiac arrest syndrome by providing 24/7 therapeutic mild hypothermia, urgent cardiac catheterization and percutaneous coronary intervention, evidence-based termination of resuscitation protocols that limit premature withdrawal of care, protocol to address organ donation, commitment of cardiocerebral resuscitation training in their community, and a commitment and proven ability of data collection to assure that instituted changes result in improved survival. This newer aspect of hospital practice is an aspect that needs to be embraced by either becoming a Cardiac Receiving Center or partnering with other hospitals that can provide this critically important service. Clin. Cardiol. 2012 doi: 10.1002/clc.21992
The authors have no funding, financial relationships, or conflicts of interest to disclose.
Discovery, Synthesis, and in vitro Evaluation of West Nile Virus Protease Inhibitors Based on the 9,10-Dihydro-3H,4aH-1,3,9,10a-tetraazaphenanthren-4-one Scaffold
Abstract
West Nile virus (WNV), a member of the Flaviviridae family, is a mosquito-borne pathogen that causes a great number of human infections each year. Neither vaccines nor antiviral therapies are currently available for human use. In this study, a WNV NS2B–NS3 protease inhibitor with a 9,10-dihydro-3H,4aH-1,3,9,10a-tetraazaphenanthren-4-one scaffold was identified by screening a small library of non-peptidic compounds. This initial hit was optimized by solution-phase synthesis and screening of a focused library of compounds bearing this scaffold. This led to the identification of a novel, uncompetitive inhibitor (1a40, IC50=5.41±0.45 μM) of WNV NS2B–NS3 protease. Molecular docking of this chiral compound onto the WNV protease indicates that the S enantiomer of 1a40 appears to interfere with the productive interactions between the NS2B cofactor and the NS3 protease domain; (S)-1a40 is a preferred isomer for inhibition of WNV NS3 protease.
Running cofactor interference: In vitro assays with West Nile virus (WNV) NS2B–NS3 protease resulted in the discovery of 9,10-dihydro-3H,4aH-1,3,9,10a-tetraazaphenanthren-4-ones as a new class of inhibitors of this enzyme. Optimization of the lead compound led to an uncompetitive WNV NS2B–NS3 inhibitor with an IC50 value of 5.41±0.45 μM.
Brain-derived neurotrophic factor as a regulator of systemic and brain energy metabolism and cardiovascular health
Overweight sedentary individuals are at increased risk for cardiovascular disease, diabetes, and some neurological disorders. Beneficial effects of dietary energy restriction (DER) and exercise on brain structural plasticity and behaviors have been demonstrated in animal models of aging and acute (stroke and trauma) and chronic (Alzheimer's and Parkinson's diseases) neurological disorders. The findings described later, and evolutionary considerations, suggest brain-derived neurotrophic factor (BDNF) plays a critical role in the integration and optimization of behavioral and metabolic responses to environments with limited energy resources and intense competition. In particular, BDNF signaling mediates adaptive responses of the central, autonomic, and peripheral nervous systems from exercise and DER. In the hypothalamus, BDNF inhibits food intake and increases energy expenditure. By promoting synaptic plasticity and neurogenesis in the hippocampus, BDNF mediates exercise- and DER-induced improvements in cognitive function and neuroprotection. DER improves cardiovascular stress adaptation by a mechanism involving enhancement of brainstem cholinergic activity. Collectively, findings reviewed in this paper provide a rationale for targeting BDNF signaling for novel therapeutic interventions in a range of metabolic and neurological disorders.
Evidence-Based Postoperative Pain Management After Laparoscopic Colorectal Surgery
Abstract
Aim: The aim of this systematic review was to evaluate the available literature on the management of pain after laparoscopic colorectal surgery.
Method: Randomized studies, published in English between January 1995 and July 2011, assessing analgesic and anesthetic interventions in adults undergoing laparoscopic colorectal surgery, and reporting pain scores, were retrieved from the EMBASE and MEDLINE databases. Efficacy and adverse effects of analgesic techniques was assessed. The recommendations were based on procedure-specific evidence from a systematic review and supplementary transferable evidence from other relevant procedures.
Results: Of the 170 randomized studies identified, 12 studies were included. Overall, all approaches including ketorolac, methylprednisolone, intraperitoneal instillation of ropivacaine, intravenous lidocaine infusion, intrathecal morphine, and epidural analgesia improved pain relief, reduced opioid requirements and improved bowel function. However, there were significant differences in the study designs and the variables evaluated, precluding quantitative analysis. The L’abbe plots of the data from the epidural analgesia studies included in this review indicate that the pain scores in the non-epidural groups, although higher than those in the epidural groups, were within an acceptable level (i.e., <4/10).
Conclusion: Infiltration of surgical incisions with local anaesthetic at the end of surgery, systemic steroids, conventional nonsteroidal anti-inflammatory drugs or cyclooxygenase-2-selective inhibitors in combination with paracetamol with opioid used as rescue are recommended. Intravenous lidocaine infusion is recommended, but not as first line of therapy. However, neuraxial blocks (i.e., epidural analgesia and spinal morphine) are not necessary based on high risk:benefit ratio.
© 2012 The Authors Colorectal Disease © 2012 The Association of Coloproctology of Great Britain and Ireland
Septic shock in a patient infected with Rickettsia sibirica mongolitimonae, Spain
Clin Microbiol Infect
Abstract
In 1996, the first human case of infection by Rickettsia sibirica subsp. mongolitimonae was described in France. Subsequently, other human cases were reported in the same country. The acronym LAR (lymphangitis-associated rickettsiosis) has been proposed to designate this disease because lymphangitis is one of the main clinical manifestations. Later, a few more cases were described in Portugal, South Africa, Egypt, Greece and Spain. We report a case of R. sibirica mongolitimonae infection as a cause of septic shock in a Spanish patient living in La Rioja (northern Spain). In addition, the broad clinical spectrum of this tick-borne disease is discussed.
Clinical impact of HSV-1 detection in the lower respiratory tract from hospitalized adult patients
Clin Microbiol Infect
Abstract
The occurrence and clinical impact of herpes simplex virus (HSV) were evaluated in 342 bronchoalveolar lavage specimens from 237 patients. HSV-1 and HSV-2 were detected in 32.1% and <1% of patients, respectively. A significant difference of HSV-1 prevalence and load was found in relation to admission to intensive care unit, mechanical ventilation and mortality within 28 days; in particular, a viral load ≥105 copies/mL bronchoalveolar lavage fluid was significantly associated with critical features. No association was found with immune status or other characteristics. Nine of 21 (42.9%) cases of ventilator-associated pneumonia were positive for HSV-1, with poor outcome in six.
Changes in problem-based and routine-based healthcare attendance: a comparison of three national dental health surveys
Abstract
Background
Healthcare utilization either may be guided by a preventive orientation leading to regular visits to the doctor, or it may be triggered by impaired health. Using data from three German national surveys, we wanted to examine whether the effects of income on the utilization of dental health services increased over time owing to the considerable decrease in insurance coverage over the years and the increase in higher out-of-pocket costs from patients.
Methods
Data from three national dental health surveys (1989, 1997 and 2005) were used. The data of all respondents aged between 35 and 44 years were available, and the number of caries-free and unrestored healthy teeth was used as outcome.
Results
Over the years, the proportion of routine attenders increased considerably, and the dental health measure used indicates the improvement. The least educated respondents and those with the lowest income profited less than other groups. In spite of higher copayments, the effects of income on the utilization of dental care did not increase over time. Regarding the results of education, a significant effect was only found in the study from 2005. No clear differences between routine- and problem-oriented attenders emerged with respect to the dental health measure chosen.
Conclusions
Material conditions and education had effects on utilization behaviour. Contrary to expectation, increasing copayments did not yield higher effects of income on healthcare utilization.
Is the wait-for-patient-to-come approach suitable for African newcomers to Alberta, Canada?
Abstract
Objectives
A qualitative study was conducted to identify psychosocial barriers to providing and obtaining preventive dental care for preschool children among African recent immigrants.
Methods
Seven focus groups were conducted with 48 mothers of 3- to 5-year-old children from Ethiopian, Eritrean, and Somali communities in Edmonton. Participants had lived in Canada for 5 years or less. Three debriefing interviews were conducted with the community health workers who facilitated the focus groups in participants' first languages. Data analysis consisted of assigning codes, grouping codes into existing or new categories of barriers, grouping identified categories into domains, and organizing categories and domains around a general perspective of psychosocial barriers to prevention of caries.
Results
Barriers to prevention of early childhood caries (ECC) were associated with home-based prevention, early detection, and access to professional care. Barriers to parental prevention were related to health beliefs, knowledge, oral health approach, and skills. Barriers to early detection included perceived role of caregivers and dentists, perceived identity of ECC, ways of detecting cavities, and parental self-efficacy. Access barriers were related to parental knowledge of preventive services, attitudes toward dentists and dental services, English skills, and external constraints concerned dental insurance, social support, time, and transportation.
Conclusions
Preventive interventions should be aimed at assisting primary caregivers with providing and obtaining adequate dental care for their children through enhancing oral health literacy, developing new set of oral health–related skills, reducing environmental constraints, and strengthening their intention of obtaining professional preventive dental services.
Overexpression of RNA helicase p68 protein in cutaneous squamous cell carcinoma
Summary
Background. RNA helicase p68 is a prototypic DEAD-box RNA helicase. Recent studies indicate that p68 plays important role in cancer development and progression. However, the role of p68 protein expression in cutaneous squamous cell carcinoma (SCC) remains unknown.
Aim. To elucidate the expression of p68 protein in cutaneous SCC.
Methods. The level of p68 protein was examined by double immunofluorescent staining in 24 samples of human cutaneous SCC tissue specimens and their adjacent tissues and in 6 normal foreskin samples to compare the expression of p68 with that of Ki-67.
Results. Overexpression of p68 protein was seen in all 24 SCC cases (100%), whereas very low expression of p68 was detected in normal foreskin. Moreover, p68 protein expression was higher in cases of cutaneous SCC with metastasis than in cases without metastasis. Additionally, p68 had a similar expression pattern to that of Ki-67.
Conclusion. The high frequency of p68 expression in cutaneous SCC indicates that p68 might be involved in the development and progression of cutaneous SCC.
Orofacial granulomatosis: three case reports illustrating the spectrum of disease and overlap with Crohn's disease
Summary
We report three cases of orofacial granulomatosis (OFG) to illustrate the spectrum of this disease, and to discuss the appropriate management steps, consider its overlap with Crohn's disease (CD) and raise its awareness among paediatric dermatologists. The term ‘orofacial granulomatosis’ was first used in 1985 to describe granulomas in the orofacial region in the absence of any recognized systemic condition. It is uncommon but becoming increasingly recognized in children. The clinical features of the disease may vary greatly, and often present with subtle changes that can be missed. There is a debate about whether OFG exists as a separate condition or whether it is an oral feature of CD, as some patients go on to develop CD several years later. Identifying those most at risk is important, as ongoing investigations may be necessary. The three cases presented in this series illustrate the range of disease signs and symptoms, and the investigations required.
Characteristics of older and younger patients with suspected paracetamol toxicity
Aim: The aim of this study was to compare the characteristics of older and younger patients with suspected paracetamol toxicity.
Methods: A retrospective audit of the medical records of older (≥65 years, n= 25) and younger (20–30 years, n= 50) patients with a detectable paracetamol level at a Sydney hospital.
Results: Older patients showed a different clinical pattern of suspected paracetamol toxicity and were more likely than younger patients to have multifactorial elevation of liver function tests. Additionally, older age was more likely to be associated with chronic therapeutic paracetamol dosing (71% older, 6% younger, P < 0.001), or with accidental toxic exposure (90% older, 29% younger, P < 0.001), while younger patients were more likely to have a deliberate high-dose exposure (10% older, 71% younger, P < 0.001).
Conclusions: The age-related differences in paracetamol exposure, paracetamol levels and liver function tests described in this population should be considered when ordering and interpreting paracetamol levels.
Calciphylaxis with normal renal function: treated with intravenous sodium thiosulfate
Summary
Calciphylaxis is a rare and potentially life-threatening condition. It is thought to result from arterial calcification causing complete vascular occlusion and subsequent cutaneous infarction. Most often, it is a complication of end-stage renal failure or hyperparathyroidism; without either of these associated conditions, it is extremely rare. We report a case of calciphylaxis in a 58-year-old white British man, who had received long-term oral prednisolone for asthma control, with prophylactic calcium supplementation. There was no history of renal failure, and the patient’s parathyroid function was normal. He was found to be heterozygous for the Factor V Leiden mutation. The acute presentation was seemingly precipitated by an episode of trauma and subsequent compression bandaging. The patient responded promptly to intravenous sodium thiosulfate. To our knowledge, this is the first case with no history of renal failure and normal parathyroid function, precipitated by compression bandaging and with an associated Factor V Leiden mutation.
Pagetoid reticulosis in a prepubescent boy successfully treated with photodynamic therapy
Summary
Pagetoid reticulosis or Woringer–Kolopp disease (WKD) is a rare variant of mycosis fungoides, consisting of localized patches or plaques containing intraepidermal proliferations of neoplastic T cells in a pagetoid distribution (similar to that of the adenocarcinomatous cells found in Paget disease of the nipple), which typically affects middle-aged and elderly men. We report a trial of photodynamic therapy (PDT) with topical aminolaevulinic acid (ALA), carried out on a 10-year-old boy with a solitary lesion of WKD on his foot, to avoid the long-term problems associated with the typical treatments for WKD of surgery and/or local irradiation. The plaque progressively flattened during treatment, and after nine PDT sessions over 13 months, the patient was clinically free of disease. PDT may be a viable alternative to surgery and local irradiation for localized cutaneous T-cell lymphoma, including WKD, especially in younger patients.
Reaction to biological drugs: infliximab for the treatment of toxic epidermal necrolysis subsequently triggering erosive lichen planus
Summary
Toxic epidermal necrolysis (TEN) is a rare, life-threatening skin reaction for which there is currently has no standardized treatment, despite its significant mortality. Biological agents such as tumour necrosis factor (TNF)-α antagonists are emerging as a novel treatment for patients with TEN. We report a 32-year-old woman who developed TEN secondary to sulfasalazine, which was treated with infliximab. The infliximab treatment subsequently triggered erosive lichen planus (LP) involving the mouth and vulva. Clinicians should be aware that TNF-α antagonists can cause LP as a paradoxical complication of treatment.
Anti-neutrophil cytoplasmic antibody-positive neutrophilic dermatosis of the dorsal hands
Summary
Neutrophilic dermatosis of the hands is a localized variant of Sweet syndrome (SS). It was first reported in 1995, and is an uncommon condition, with < 100 cases reported to date. The female preponderance, morphological and histological features, and response to treatment are similar to SS, but it differs in its distribution on the body. There may also be a lack of systemic features and inconsistent laboratory findings. Significantly, about half of all cases are associated with haematological problems, i.e. myelodysplasia and leukaemia. Other cases may be associated with ulcerative colitis or solid tumours. We describe a case of a 71-year-old man with neutrophilic dermatoses of the hands, who also had involvement of the lips. There was an associated rise in his anti-neutrophil cytoplasmic antibody level, which corresponded with the activity of the disease.
Liquid chromatography–mass spectrometry method for the analysis of 1,4-dimethylpyridinium in rat plasma – application to pharmacokinetic studies
ABSTRACT
A sensitive and specific liquid chromatography electrospray ionization–mass spectrometry method for determination of 1,4-dimethylpyridinium (1,4-DMP) in rat plasma has been developed and validated. Chromatography was performed on an Aquasil C18 analytical column (4.6 × 150 mm, 5 µm, Thermo Scientific, Rockford, IL, USA) with isocratic elution using a mobile phase containing acetonitrile and water with an addition of 0.1% of formic acid. Detection was achieved by an Applied Biosystems MDS Sciex (Concord, Ontario, Canada) API 2000 triple quadrupole mass spectrometer. Electrospray ionization was used for ion production. The limit of detection in the single ion monitoring mode was found to be 10 ng/mL. The limit of quantification was 50 ng/mL. The precision and accuracy for both within-day and between-day determination of 1,4-dimethylpyridinium was 2.4–7.56 and 90.93–111.48%. The results of this analytical method validation allow pharmacokinetic studies to be carried out in rats. The method was used for the pilot study of the pharmacokinetic behavior of 1,4-DMP in rats after intravenous administration. Copyright © 2012 John Wiley & Sons, Ltd.
Behavioral symptoms in mild cognitive impairment as compared with Alzheimer's disease and healthy older adults
Background
Mild cognitive impairment (MCI) is a clinical concept that categorizes subjects who are in an intermediate cognitive state between normal aging and dementia. The aim of this study is to characterize behavior in MCI compared with Alzheimer's disease (AD) and healthy older patients.
Design
A cross-sectional analysis of baseline data from a prospective, longitudinal study on behavioral symptoms of dementia and MCI was performed. The study population consisted of 270 MCI, 402 AD patients, and 108 healthy controls. Behavioral assessment was performed by means of Middelheim Frontality Score, Behavioral Pathology in Alzheimer's Disease Rating Scale, Cohen-Mansfield Agitation Inventory, and Cornell Scale for Depression in Dementia.
Results
Moderate-to-severe behavioral symptoms were present in 13% of MCI patients, as compared with 39% in AD patients and 3% in controls (p < 0.001). The general severity of behavioral symptoms was intermediate between controls and AD patients.
The three most frequent symptoms in MCI patients were aggressiveness (49%), affective disturbance (45%), and anxiety (38%); in AD patients, the most frequent symptoms were aggressiveness (60%), activity disturbances (54%), and psychosis (40%).
The prevalence and severity of frontal lobe symptoms, aggressiveness, activity disturbances, and delusions was intermediate between normal aging and AD. In addition, the severity of physically non-aggressive and verbally agitated behavior and the severity of depressive symptoms were also intermediate.
Conclusions
The behavioral profile of MCI patients is characterized as an intermediate state between normal aging and AD for the prevalence and severity of certain behavioral symptoms. Follow-up is ongoing to test the hypothesis that behavioral disturbances in MCI predict progression to dementia. Copyright © 2012 John Wiley & Sons, Ltd.
Effect of Processing on Microstructure and Physical Properties of Three Nickel-Based Superalloys with Different Hardening Mechanisms
Abstract
The nickel-based superalloys Inconel alloy 600, Udimet alloy 720, and Inconel alloy 718 were produced by electron beam melting (EBM), casting, and directional solidification (DS). The distance between dendrites and the size of the precipitates indicated the difference in solidification rates between the three processes. In this study, the solidification rate was fastest with EBM, closely followed by casting, whereas it was much slower with DS. In the directional solidified materials the <100> direction was the fastest and thus, preferred growth direction. The EBM samples show a sharp (001)[100] texture in the building direction and in the two scanning directions of the electron beam. Macrosegregation was observed in some cast and directionally solidified samples, but not in the EBM samples. The melting temperatures are in good agreement with literature and the narrow melting interval of IN600 compare to UD720 and IN718 might reduce the risk of incipient melting during EBM processing. Porosity was observed in the EBM samples and the reasons are discussed. However, EBM seems to be a feasible process route to produce nickel-based superalloys with well-defined texture, no macrosegregation and a rapidly solidified microstructure.
The nickel-based superalloys Inconel alloy 600, Udimet alloy 720, and Inconel alloy 718 are produced by electron beam melting (EBM), casting, and directional solidification. Material differences due to the different processing routes are investigated. EBM seems to be a feasible way to produce superalloys with well-defined texture, no macrosegregation and a rapidly solidified microstructure.
The LINA cohort: indoor chemical exposure, circulating eosinophil/basophil (Eo/B) progenitors and early life skin manifestations
Abstract
Background
Hematopoietic progenitor cells, especially those committed to the Eo/B lineage, are known to contribute to allergic inflammation.
Objective
The aim of the present study was to investigate whether environmental factors are associated with changes in numbers of circulating Eo/B progenitors at one year of age.
Methods
Peripheral blood from 60 one-year old children enrolled in the LINA (Lifestyle and environmental factors and their Influence on Newborns Allergy risk) birth cohort was assessed for Eo/B progenitor cells (Eo/B CFU) by standardized and validated methylcellulose assays. Frozen peripheral blood mononuclear cells (PBMC) were cultured in the presence of IL-3, IL-5 or GM-CSF, and Eo/B CFUs enumerated. Clinical outcomes and exposure to environmental tobacco smoke (ETS) were documented by standardized questionnaires, and indoor volatile organic compound (VOC) concentrations were assessed by passive sampling.
Results
Children with skin manifestations (atopic dermatitis or cradle cap) within the first year of life had higher numbers of circulating IL-3-, IL-5- or GM-CSF-stimulated Eo/B CFUs (p<0.05) at one year. In children with cradle cap, a positive correlation was found between Eo/B CFUs and exposure to ETS-related VOCs during pregnancy or at one year of age (p<0.05).
Conclusions And Clinical Relevance
This is the first demonstration that environmental exposures are positively associated with levels of circulating Eo/B progenitors. The recruitment and differentiation of Eo/B progenitors in response to environmental triggers may play a role in the development of skin manifestations during the first year of life.
© 2012 Blackwell Publishing Ltd
QUALITY OF LIFE AND CONTROL OF ALLERGIC RHINITIS IN PATIENTS FROM REGIONS BEYOND WESTERN EUROPE AND THE USA
Abstract
There is comparatively little information on health-related quality of life (HRQoL) in subjects with allergic rhinitis (AR) or allergic rhinoconjunctivitis (AR/C) in countries beyond western-Europe and North America. The primary aim of this investigation was therefore to review and assess the information in the public domain on HRQoL in AR/C patients from diverse regions of the world, represented by different countries; including Argentina, Australia, Brazil, Russia, Singapore, South Africa and Turkey. Secondly, in view of the absence of a standardised definition for “AR control”, the review aimed to determine whether a working definition of AR/C can be inferred from validated tests or other instruments documented to date. Despite the comparatively low number of studies, this review demonstrated that overall the symptoms of AR/C impair the HRQoL of patients in these regions by adversely impacting sleep, daily activities, physical and mental status and social functioning, similar to that demonstrated in much larger numbers of studies of AR/C patients in Europe and the US. Furthermore, the findings of the review suggest that “overall” control of the disease should encompass reduction of nasal and ocular symptoms, as well as improvements in HRQoL, comorbid conditions, and cognition. Although some instruments are currently available for measuring control of AR none are capable of assessing all these aspects, emphasizing the need to develop appropriate new instruments.
© 2012 Blackwell Publishing Ltd
Why are defensive toxins so variable? An evolutionary perspective
Defensive toxins are widely used by animals, plants and micro-organisms to deter natural enemies. An important characteristic of such defences is diversity both in the quantity of toxins and the profile of specific defensive chemicals present. Here we evaluate evolutionary and ecological explanations for the persistence of toxin diversity within prey populations, drawing together a range of explanations from the literature, and adding new hypotheses. We consider toxin diversity in three ways: (1) the absence of toxicity in a proportion of individuals in an otherwise toxic prey population (automimicry); (2) broad variation in quantities of toxin within individuals in the same population; (3) variation in the chemical constituents of chemical defence. For each of these phenomena we identify alternative evolutionary explanations for the persistence of variation. One important general explanation is diversifying (frequency- or density-dependent) selection in which either costs of toxicity increase or their benefits decrease with increases in the absolute or relative abundance of toxicity in a prey population. A second major class of explanation is that variation in toxicity profiles is itself nonadaptive. One application of this explanation requires that predator behaviour is not affected by variation in levels or profiles of chemical defence within a prey population, and that there are no cost differences between different quantities or forms of toxins found within a population. Finally, the ecology and life history of the animal may enable some general predictions about toxin variation. For example, in animals which only gain their toxins in their immature forms (e.g. caterpillars on host plants) we may expect a decline in toxicity during adult life (or at least no change). By contrast, when toxins are also acquired during the adult form, we may for example expect the converse, in which young adults have less time to acquire toxicity than older adults. One major conclusion that we draw is that there are good reasons to consider within-species variation in defensive toxins as more than mere ecological noise. Rather there are a number of compelling evolutionary hypotheses which can explain and predict variation in prey toxicity.
Investigation of the metabolic biotransformation of substance P in liver microsomes by liquid chromatography quadrupole ion trap mass spectrometry
ABSTRACT
Substance P (SP) belongs to the tachykinin family and plays an essential role in pain transmission and in neurogenic inflammation. It can be detected in the central and peripheral nervous systems. The objectives of this study were to establish SP metabolic stability in liver microsomes in three species (rat, mouse and human), and identify and characterize SP metabolites by LC-MS/MS. Endogenous peptide metabolism is not well documented and this is particularly true for neuropeptides participating in neurogenic inflammation. In vitro, T1/2 results in pooled liver microsomes were 9.2, 5.6 and 18.6 min for rat, mouse and human liver microsomes, respectively. Five major SP metabolites were identified and quantified, including C-terminal SP fragments SP3–11, SP5–11, SP6–11, SP8–11 as well as N-terminal fragment SP1–7. The results suggest significant differences between species in SP metabolite concentrations. Consequently, the metabolic profile of each species is distinctive and may have a significant impact on biomolecular mechanisms involved in specific pathophysiological changes. Copyright © 2012 John Wiley & Sons, Ltd.
Simultaneous determination of sitagliptin and simvastatin in human plasma by LC-MS/MS and its application to a human pharmacokinetic study
ABSTRACT
A simple, rapid and sensitive liquid chromatography–tandem mass spectrometric (LC-MS/MS) assay method has been developed and validated for simultaneous quantification of sitagliptin and simvastatin in human plasma. Carbamazepine was used as an internal standard (IS). The analytes and IS were extracted from the human plasma by liquid–liquid extraction technique. The reconstituted samples were chromatographed on an Alltima HP C18 column using an isocratic solvent mixture [acetonitrile–5 m m ammonium acetate (pH 4.5), 85:15 (v/v)] at a flow rate of 1.0 mL/min. Method validation was performed as per Food and Drug Administration guidelines and the results met the acceptance criteria. The calibration curves obtained were linear (r2 ≥ 0.99) over the concentration range of 0.10–501 and 0.05–105 ng/mL for sitagliptin and simvastatin, respectively. The results of the intra- and inter-day precision and accuracy studies were well within the acceptable limits. Both the analytes were found to be stable in a battery of stability studies. The method is precise and sensitive enough for its intended purpose. A run time of 3.0 min for each sample made it possible to analyze more than 300 plasma samples per day. The developed assay was successfully applied to a pharmacokinetic study in human volunteers. Copyright © 2012 John Wiley & Sons, Ltd.
Phospholipid profiling of 57 soybean (Glycine max) varieties by high-performance liquid chromatography–tandem mass spectrometry and principal component analysis to classify Korean soybean germplasm
ABSTRACT
Phospholipids (PLs) in 57 varieties of soybeans were profiled by high-performance liquid chromatography–electrospray ionization-tandem mass spectrometry and principal component analysis (PCA) to discriminate PL-rich soybeans. The PL calibration curves showed linearity with correlation coefficients >0.9964. The recoveries at 5 mg/L spiked level ranged from 72.8 to 86.7% and those at 12.5 mg/L from 78.2 to 85.1%. The repeatability at a 5 mg/L spiked level ranged from 2.5 to 7.0% and those at 12.5 mg/L from 1.2 to 3.9%. The average total PL content in the 57 soybean varieties was about 35.3 mg/kg. The total PL content was the highest in Aodaiz (35, 48.7 ± 1.4 mg/kg) and the lowest in Poongsannamul (56, 16.0 ± 0.7 mg/kg). The PCA showed that RS-78sun (42), Gyeongsang #1 (3) and Aodaiz (35) are the most improved varieties of the investigated 57 varieties from the viewpoint of PL content. Copyright © 2012 John Wiley & Sons, Ltd.
Sunday, April 29, 2012
Gingivitis and plaque scores of 8- to 11-year-old Burmese children following participation in a 2-year school-based toothbrushing programme
To cite this article: Int J Dent Hygiene10, 2012; 163–168 DOI: 10.1111/j.1601-5037.2012.00553.x Rosema NAM, van Palenstein Helderman WH, van der Weijden GA. Gingivitis and plaque scores of 8- to 11-year-old Burmese children following participation in a 2-year school-based toothbrushing (SBTB) programme.
Abstract:
Aim: The present study assessed whether gingivitis and plaque scores of 8- to 11-year-old school children who participated in a SBTB programme for 2 years were lower than those of children who did not participate in the programme.
Material and methods: The present study was performed using an examiner-blind, parallel group design and was performed in Burma (Myanmar) in 2006. Three of the five schools where daily SBTB programmes took place after lunch and which were performed under teacher supervision were randomly selected; three non-participating schools (non-SBTB) from the same area were assigned as controls. Twenty-five children per school were examined for gingivitis (bleeding on marginal probing) and plaque (Quigley & Hein).
Results: In total, 150 8- to 11-year-old children participated, with 75 children in either group. The test group (SBTB) exhibited an overall mean bleeding score of 0.76. For the control group (non-SBTB), this score was 0.83. With respect to the overall mean plaque scores, the test group exhibited a score of 2.93, whereas the control group exhibited a score of 2.91. No statistically significant differences between the test and the control group were observed.
Conclusion: The present study did not reveal a statistically significant effect of daily SBTB programmes in 8- to 11-year-old school children with respect to gingivitis and plaque scores.
Conformational Flexibility and Absolute Stereochemistry of (3R)-3-hydroxy-4-aryl-β-lactams Investigated by Chiroptical Properties and TD-DFT Calculations
ABSTRACT
The effect of conformational flexibility on the chiroptical properties of a series of synthetic (3R)-3-hydroxy-4-aryl-β-lactams of known stereochemistry (1–6) was investigated by means of electronic circular dichroism (ECD) measurements and time-dependent density functional theory (TD-DFT) calculations. The application of the β-lactam sector rules allowed a correct stereochemical characterization of these compounds, with the exception of a thienyl-substituted derivative (cis-6). TD-DFT calculations yielded accurate predictions of experimental ECD spectra and [α]D values, allowing us to assign the correct absolute configuration to all the investigated compounds. A detailed analysis of the β-lactam ring equilibrium geometry on optimized conformers identified regular patterns for the arrangement of atoms around the amide chromophore, confirming the validity of the β-lactam sector rules. However, relevant variations in theoretical chiroptical properties were found for compounds bearing a heterocyclic substituent at C4 or a phenyl substituent at C3, whose conformers deviate from these regular geometric patterns. This behavior explains the failure of the β-lactam sector rules in cis-6. This study showed the importance of conformational flexibility for the determination of chiroptical properties and highlighted the strengths and weaknesses of the different methods for the stereochemical characterization of chiral molecules in solution. Chirality 00:000-000, 2012. © 2012 Wiley Periodicals, Inc.
Molecular Structure Determination Using Chiroptical Spectroscopy: Where We May Go Wrong?
ABSTRACT
Chiroptical spectroscopy is being widely used for determining the three-dimensional molecular structures (i.e., absolute configurations and conformations) of chiral molecules. The general procedure used with any of the chiroptical spectroscopic methods is to analyze the experimental data using corresponding quantum chemical predictions. Such analysis involves multiple steps, including consideration of conformations, solvent effects, electronic transitions, stereoisomers, and experimental artifacts, each of which possesses certain limitations. These limitations, when not recognized or properly taken into account, may lead to incorrect conclusions. This review emphasizes on selected examples that illustrate the potential limitations in utilizing the chiroptical spectroscopic methods. The examples used include hibiscus acid dimethylester, hibiscus acid disodium salt, 3,3′-diphenyl-[2,2′-binaphthalene]-1,1′-diol, tartaric acid esters, and 6,6′-dibromo-[1,1′-binaphthalene]-2,2′-diol. Chirality 00:000-000, 2012. © 2012 Wiley Periodicals, Inc.
Analysis of Chirality by Femtosecond Laser Ionization Mass Spectrometry
ABSTRACT
Recent progress in the field of chirality analysis employing laser ionization mass spectrometry is reviewed. Emphasis is given to femtosecond (fs) laser ionization work from the author's group. We begin by reviewing fundamental aspects of determining circular dichroism (CD) in fs-laser ionization mass spectrometry (fs-LIMS) discussing an example from the literature (resonant fs-LIMS of 3-methylcyclopentanone). Second, we present new data indicating CD in non-resonant fs-LIMS of propylene oxide. Chirality 00:000–000, 2012. © 2012 Wiley Periodicals, Inc.
A questionnaire survey of patient experience with the Rheumatology Monitoring Clinic in Singapore
Abstract
Aim
The concept of a pharmacist/advanced practice nurse (APN)-led Rheumatology Monitoring Clinic (RMC) is a novel service in Singapore; we therefore conducted a questionnaire survey of patient experience.
Methods
Patients attending the RMC were provided with a set of questionnaires. As a substudy, a separate questionnaire was given to the rheumatologists and therapists conducting the RMC.
Results
Of the 105 patients surveyed, a total of 97 (92.4%) patients were satisfied/strongly satisfied with the overall service, and none were dissatisfied; 96% felt that the pharmacists/APNs provided clear, detailed information about their disease and medication, while 92% of patients were confident they knew what side-effects were possible. Ninety-two percent and 93% of patients were more likely to adhere to treatment, and were willing to come back for follow-up at the RMC, respectively. There was no difference in patient satisfaction in the average Likert summed scores, between the pharmacists and APNs. Age, gender, ethnicity and underlying disease did not exert any influence on the responses. All the rheumatologists surveyed were satisfied with the patients' management and the professionalism of the therapists. They opined that the RMC freed up time for them to see more complex cases. All the pharmacists/APNs concurred that the referrals were appropriately selected.
Conclusions
We established the acceptability of a non-physician-led clinic in our local setting and highlighted the usefulness of having a routine clinic for monitoring medication toxicity and patient education. The RMC received positive feedback from patients, rheumatologists and allied health therapists, with a high degree of satisfaction among the respondents.
A multicenter study of clinical and laboratory findings of palindromic rheumatism in Iran
Abstract
Objective
Considering demographic, clinical and laboratory characteristics of palindromic rheumatism and finding out the difference between rheumatoid factor and anti-cyclic citrullinated peptide positive and negative cases of palindromic rheumatism in Iran.
Methods
In this cross-sectional and multicenter study, patients with intermittent arthritis were evaluated by a rheumatologist for palindromic rheumatism. Diagnosis of palindromic rheumatism was made after ruling out other causes of recurrent arthritis, and the fulfillment of the Pasero and Barbieri criteria. Then the demographic and clinical characteristics were recorded and compared in rheumatoid factor and anti-cyclic citrullinated peptide positive and negative patients.
Results
Of the 69 patients with palindromic rheumatism, 35 were men and 34 were women. The mean ages of the patients at the time of diagnosis were 38.5 ± 14.6 years. The mean attack intervals and duration of the attacks were 66.3 ± 38.4 days and 3.9 ± 3.3 days, respectively. The most commonly involved joints were knees, metacarpophalangeals and proximal interphalangeals. Rheumatoid factor in 46.4% and anti-cyclic citrullinated peptide in 42% of the cases were positive. Palindromic patients with positive anti-cyclic citrullinated peptide had higher age, shorter duration of disease, shorter duration of attacks, more frequent attacks and more metacarpophalangeal joints involvement.
Conclusions
Rheumatoid factor and anti-cyclic citrullinated peptides were found in a high proportion of patients with palindromic rheumatism. The clinical features of the disease in our study were different in rheumatoid factor and anti-cyclic citrullinated peptide positive and negative patients.
Frequency of iridocyclitis in patients with early psoriatic arthritis: a prospective, follow up study
Abstract
Objective
The occurrence of iridocyclitis (IC) in early psoriatic arthritis (PsA) has been rarely assessed. The primary end-point of this study was to evaluate the frequency of IC at onset in patients with early PsA.
Methods
We evaluated the frequency of IC in a clinical series of consecutive, new outpatients with early PsA observed between January 2000 and December 2009. All patients met the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria for PsA and had a disease duration ≤12 months. The following clinical patterns were considered: peripheral PsA (oligoarthritis ≤4 and polyarthritis ≥5 involved joints), axial PsA and mixed. IC diagnosis was made by the ophthalmologist. Follow-up visits were scheduled at baseline and every 4 months with interval shortening in the case of urgent clinical problems.
Results
Two hundred and forty-two patients, 137 (57%) women and 105 (43%) men (mean age 50.33 ± 11.7 years; mean symptom duration 9.38 ± 3.1 months) were studied. One hundred and thirty-two (51%) patients had peripheral PsA, 41 (17%) axial and 69 (28%) mixed. Twenty-six episodes of IC were recorded at diagnosis in 22 (9%) patients, 17 (77.3%) female and five (22.7%) male; 11 (50%) patients had peripheral PsA, two (9.1%) axial, and nine (40.9%) mixed; 5/22 (22.7%) patients were B27-positive. IC recurred in 2/22 (9%) patients over the follow-up period. Mean follow-up duration was 51 ± 23.2 months. Dactylitis was significantly more frequent in patients with IC compared to those without this feature (P = 0.032).
Conclusion
IC occurred in 9% of 242 patients with early PsA with no association with the clinical pattern and B27 positivity. This frequency is higher than previously reported.
Validation of the scleroderma health assessment questionnaire and quality of life in English and Chinese-speaking patients with systemic sclerosis
Abstract
Aims
To perform cross-cultural adaptation and validation of the Scleroderma Health Assessment Questionnaire (S-HAQ) and Systemic Sclerosis Quality of Life scale (SSc-QoL) in English and Chinese-speaking patients with SSc.
Methods
In this Institutional Review Board approved study, patients seen at the rheumatology outpatient clinics were consecutively recruited over a 10-month period. We evaluated: (i) test–retest reliability using the intraclass correlation coefficient (ICC); (ii) known-groups construct validity by stratifying patients according to organ involvement and symptom severity; and (iii) convergent validity using Spearman's correlation with Short Form 36 version 2 (SF36v2).
Results
Forty-nine SSc patients completed the questionnaires: 26 Chinese, 23 English; 30 self-administered, 19 interviewer-administered, of which 35 responded to the retest. The SSc-QoL, HAQ Disability Index, intestinal Visual Analogue Scale (VAS), breathing VAS and overall disease severity VAS demonstrated high reliability (ICCs 0.71–0.93). The intestinal, finger ulcer and breathing S-HAQ VASs were able to differentiate patients according to their respective organ involvement. As hypothesized, the S-HAQ correlated better with the Physical Summary Component (PCS) than the Mental Summary Component (MCS) scores of the SF36v2. The SSc-QoL also demonstrated good convergent validity with the SF36v2 scales.
Conclusion
In this pilot study, we provided preliminary evidence to demonstrate the good test–retest reliability and reasonable construct validity of S-HAQ and SSc-QoL for use in English and Chinese-speaking SSc patients. This forms the basis for future studies to assess more extensively their psychometric properties.
Kinetics of the brominated alkyl radical (CHBr2, CH3CHBr) reactions with NO2 in the temperature range 250–480 K
Abstract
The gas-phase kinetics of CHBr2 + NO2 and CH3CHBr + NO2 reactions have been studied in direct time resolved measurements using a tubular flow reactor coupled to a photoionization mass spectrometer. The radicals were generated by pulsed laser photolysis of bromoform and 1,1-dibromoethane at 248 nm. The subsequent decays of the radical concentrations were monitored as a function of [NO2] under pseudo–first-order conditions. The rate coefficients of both reactions are independent of bath gas (He) pressure and display negative temperature dependence under the conditions of 2–6 Torr pressure (He) and 250–480 K. The obtained bimolecular rate coefficients are k(CHBr2 + NO2) = (9.8 ± 0.4) × 10−12 (T/300 K)−1.65 ± 0.18 cm3 s−1 (288–483 K) and k(CH3CHBr + NO2) = (2.27 ± 0.06) × 10−11 (T/300 K)−1.28 ± 0.11 cm3 s−1 (250–483 K), with the uncertainties given as one standard error. Estimated overall uncertainties in the measured bimolecular reaction rate coefficients are ±25%. The reaction products identified were CBr2O for the CHBr2 + NO2 reaction and CHBrO and CH3CHO with minor amounts of CH3 for the CH3CHBr + NO2 reaction, respectively. © 2012 Wiley Periodicals, Inc. Int J Chem Kinet 1–11, 2012
Saturday, April 28, 2012
Supramolecular Photochirogenesis with Novel Cyclic Tetrasaccharide: Enantiodifferentiating Photoisomerization of (Z)-Cyclooctene with Cyclic Nigerosylnigerose-Based Sensitizers
ABSTRACT
Isophthalic and terephthalic acid monoesters of cyclic nigerosyl-(1→6)-nigerose (CNN), a cyclic tetrasaccharide composed of four d-glucopyranosyl residues connected by alternating α-1,3- and α-1,6-linkages, were synthesized as novel chiral supramolecular sensitizers for enantiodifferentiating photoisomerization of (Z)-cyclooctene (1Z) to planar chiral (E)-isomer (1E). Despite the saucer-shaped shallow cavity of CNN that does not immediately guarantee strong ground-state interactions with 1Z, the sensitizer-appended CNNs afforded optically active 1E in such enantiomeric excesses that are much improved than those obtained with an α-cyclodextrin analog and comparable with those obtained with a β-cyclodextrin analog. Interestingly, the enantiomeric excess values obtained were a critical function of temperature and solvent to show an inversion of the product chirality by changing the environmental variants. Nevertheless, all of the differential activation parameters calculated from the temperature-dependent enantiomeric excesses gave an excellent compensatory enthalpy–entropy relationship, indicating an operation of a single enantiodifferentiating mechanism in the present chiral photosensitization with modified CNNs. Chirality 00:000–000, 2012. © 2012 Wiley Periodicals, Inc.
Friday, April 27, 2012
Pollinating fig wasp Ceratosolen solmsi adjusts the offspring sex ratio to other foundresses
Abstract Local mate competition theory predicts that offspring sex ratio in pollinating fig wasps is female-biased when there is only one foundress, and increased foundress density results in increased offspring sex ratio. Information of other foundresses and clutch size have been suggested to be the main proximate explanations for sex ratio adjustment under local mate competition. Our focus was to show the mechanism of sex ratio adjustment in a pollinating fig wasp, Ceratosolen solmsi Mayr, an obligate pollinator of the functionally dioecious fig, Ficus hispida Linn., with controlled experiments in the field. First, we obtained offspring from one pollinator and offspring at different oviposition sequences, and found that offspring sex ratio decreased with clutch size, and pollinators produced most of their male offspring at the start of bouts, followed by mostly females. Second, we found that offspring sex ratio increased with foundress density, and pollinators did adjust their offspring sex ratio to other females in the oviposition patches. We suggest that when oviposition sites are not limited, pollinators will mainly adjust their offspring sex ratio to other foundresses independent of clutch size changes, whereas adjusting clutch size may be used to adjust sex ratio when oviposition sites are limited.