bluuebunny/crossref_metadata_2025 huggingface dataset:
Platelets from children are hyper‐responsive to activation by thrombin receptor activator peptide and adenosine diphosphate compared to platelets from adults
Authors: Yip Christina , Linden Matthew D. , Attard Chantal , Monagle Paul , Ignjatovic Vera
Published: September 2014

Platelets are crucial subcellular elements of haemostasis at sites of vascular injury and are also known to be immune mediators in pathological thrombosis. Despite the integral role of platelets in many disease processes, there is very little information available on platelet function and response to agonists in healthy children. We recently reported important differences in the interaction of platelets with monocytes in the circulation, including increased formation of monocyte‐platelet aggregates (MPAs) without concomitant increase in P‐selectin expression. Our current study investigates parameters of platelet activation (PAC‐1 binding and P‐selectin expression) and MPA formation in response to a range of physiologically relevant platelet agonists in healthy children compared to healthy adults. All parameters were significantly higher in children in response to sub‐maximal concentrations of thrombin receptor activator peptide and adenosine diphosphate, reflecting an age‐specific difference in agonist‐stimulated platelet reactivity in children. The results of our study challenge the general assumption that platelet reactivity in children is similar to adults. This finding is fundamental to investigating the role of platelets in diseases of childhood and pathogenesis of adult‐based diseases that have their origins in childhood. Our findings underscore the need for age‐specific reference ranges for platelet function in children rather than extrapolation from adult data.
Quantification of the effect of chemotherapy and steroids on risk of Pneumocystis jiroveci among hospitalized patients with adult T‐cell leukaemia
Authors: Maeda Toshiki , Babazono Akira , Nishi Takumi , Matsuda Shinya , Fushimi Kiyohide , Fujimori Kenji
Published: September 2014

This study aimed to quantify the risks of Pneumocystis pneumonia (PCP) among adult T‐cell leukaemia (ATL) patients without prophylaxis. We used hospital administrative data collected nationwide in Japan over 4 years. The research design was a retrospective cohort study. Subjects were 4369 patients diagnosed with ATL aged 18 years or older. The subjects were categorized into four treatment groups: no agent, chemotherapy, chemotherapy + steroids and steroids. We described the risks of PCP among ATL patients without prophylaxis. Risks of PCP were 3·2% for the no agent group, 9·7% for the chemotherapy group, 10·0% for the chemotherapy + steroids group and 16·6% for the steroids group. Logistic regression analyses showed that the chemotherapy, chemotherapy + steroids and steroids groups had significantly higher risk of PCP than did the no agent group [adjusted odds ratio (AOR) 3·30 (1·55–7·02), P = 0·002 for the chemotherapy group; AOR 3·35 (2·18–5·17), P < 0·001 for the chemotherapy + steroids group; AOR 6·12 (3·99–9·38), P < 0·001 for the steroids group]. In conclusion, the chemotherapy, chemotherapy + steroids and steroids groups had significantly higher risks of PCP. Prophylaxis for PCP among ATL patients being treated with chemotherapy, chemotherapy + steroids and steroids is highly recommended.
Autism spectrum disorders: perceptions of genetic etiology and recurrence risk among Taiwanese parents of affected children
Authors: Chen L.S. , Li C. , Wang C.H. , Amuta A. , Li M. , Huang T.Y. , Dhar S.U. , Talwar D. , Jung E.
Published: September 2014

In Taiwan, autism spectrum disorders (ASDs) are an emerging public health concern. The ongoing scientific progress for understanding the genetic etiology of ASD makes it increasingly important to examine how parents of children with ASD perceive the causes and recurrence risk of having another child with ASD. These perceptions may influence their family planning, attitudes toward genetic services, and willingness to take their children for ASD genetic testing. However, previous studies addressing this issue were conducted primarily in Western countries. As culture might shape an individual's views of genetic/genomic disorders, this first‐of‐its‐kind study examined the perceptions of the genetic etiology for ASD and the recurrence risk among Taiwanese parents of children affected with ASD. In‐depth, semi‐structured interviews were conducted among 39 parents having at least one child with ASD. Although the majority of participants believed that ASD has a genetic link, less than half perceived genetic factors as the cause of their own child's ASD. Moreover, most participants articulated their recurrence risk incorrectly. Some parents were concerned about their doctors' limited genomic competencies. To provide parents with better education, counseling, and support for making reproductive decisions, ASD‐related genomic education among Taiwanese physicians is needed.
Chronic adrenergic stimulation induces brown adipose tissue differentiation in visceral adipose tissue
Authors: Søndergaard E. , Gormsen L. C. , Christensen M. H. , Pedersen S. B. , Christiansen P. , Nielsen S. , Poulsen P. L. , Jessen N.
Published: September 2014

Background

Recruitment of brown adipose tissue is a promising strategy to treat obesity and Type 2 diabetes, but the physiological effects of a large amount of metabolically active brown adipose tissue in humans are unknown.

Case report

In the present paper, we report a case of massive brown adipose tissue infiltration of the visceral adipose tissue depot in a person with Type 2 diabetes with a catecholamine‐secreting paraganglioma. The patient was evaluated with [18F]‐fludeoxyglucose positron emission tomography/computed tomography on three occasions: pre‐therapy, during α‐blockade and postoperatively. During surgery, biopsies of visceral and subcutaneous adipose tissue were obtained and evaluated for brown adipose tissue. At diagnosis, brown adipose tissue glucose uptake, assessed by [18F]‐fludeoxyglucose‐positron emission tomography, was massively increased. [18F]‐fludeoxyglucose uptake was confined to known locations for brown adipose tissue, with additional uptake in the visceral adipose tissue. As a result of increased thermogenesis, resting energy expenditure was doubled. After surgical removal of the tumour, antidiabetic medicine was no longer needed, despite an 8.2‐kg weight gain.

Conclusion

These results show that human visceral adipose tissue holds an unprecedented potential for brown adipogenic differentiation; however, a detrimental effect on glucose metabolism persisted despite massive brown adipose tissue activity, with a doubling of resting energy expenditure.
Changes in cell density and morphology of selected cells of the ageing human dental pulp
Authors: Daud Sulinda , Nambiar Prabhakaran , Hossain M. Zakir , Rahman Mas Rizal Ab , Bakri Marina M.
Published: September 2014

Objectives

The aim of this study was to determine the changes in cell density and morphology of selected cells of the ageing human dental pulp.

Background

Changes in cell density and morphology of dental pulp cells over time may affect their capability to respond to tooth injury.

Materials and methods

One hundred thirty‐one extracted teeth were obtained from individuals between the ages of 6 and 80 years. The apical 1/3 of the root region was removed from all teeth prior to routine processing for producing histological slides. The histology slides were used to study the changes in cell density and morphology of selected pulp cells; odontoblasts, subodontoblasts and fibroblasts in the crown and root regions of the dental pulp. Student's t‐test and one‐way anova were used for statistical analyses.

Results

In all age groups, the cell density for all types of cells was found to be higher in the crown than in the root (p < 0.05). In general, the pulp cell density was found to decrease with age in both the crown and root regions. However, it was noted that the reduction of coronal odontoblasts occurred later in life (40–49 years) when compared to that of subodontoblasts or fibroblasts (30–39 years).

Conclusions

The density of the coronal pulp cells reduces and these cells undergo morphological changes with ageing of individuals and this may affect the pulp's ability to resist tooth injury.
Cutaneous sarcoidosis: clinicopathologic study of 76 patients from Lebanon
Authors: Ishak Rim , Kurban Mazen , Kibbi Abdul‐Ghani , Abbas Ossama
Published: September 2014

Background

Sarcoidosis is a multi‐system granulomatous disease of unknown etiology. The skin is involved in 25% of cases. Studies on cutaneous sarcoidosis from our region are lacking.

Objectives

This study was conducted to describe clinical and histopathologic findings in all patients diagnosed with cutaneous sarcoidosis at the American University of Beirut Medical Center between 1992 and 2010 and to compare findings with those published in the literature.

Methods

Clinical charts of patients with cutaneous sarcoidosis were retrospectively reviewed. Extracutaneous lesions were classified by organ involvement. Treatment was documented. Pathology specimens were reviewed.

Results

Cutaneous sarcoidosis was diagnosed in 76 Lebanese patients, 79% of whom were women. Mean age at diagnosis was 48 years. A total of 29% of patients had systemic disease that was commonly associated with lupus pernio lesions and subcutaneous sarcoidosis. The most common cutaneous lesions were sarcoidal plaques. The histopathologic features in our series did not differ from those described in the literature, except for the documented presence of a grenz zone. Interestingly, 23% of biopsy specimens contained perineural granulomas, raising the possibility of tuberculoid or borderline tuberculoid leprosy. Foreign bodies were detected in 10% of cases (all had systemic involvement), supporting the opinion that sarcoidosis and granulomatous foreign body reaction are not mutually exclusive.

Conclusions

The clinical and histopathologic features of cutaneous sarcoidosis patients in the present series are generally comparable with those published in the literature, with minor differences. Clinically, the most commonly seen lesion was plaque. Microscopically, cutaneous sarcoidosis may exhibit a grenz zone and may show perineural inflammation and foreign bodies.
Immunohistochemical expression of Bcl‐2 and Ki‐67 in oral lichen planus and leukoplakia with different degrees of dysplasia
Authors: Pigatti Fernanda Mombrini , Taveira Luís Antônio de Assis , Soares Cléverson Teixeira
Published: September 2014

Objectives

Oral lichen planus (OLP) is a chronic inflammatory disease of unknown cause. Malignant transformation in OLP lesions may be favored by changes in the expression of proteins that regulate cell proliferation and apoptosis. This study aimed to investigate these issues by immunohistochemical staining for Bcl‐2 and Ki‐67 and by correlating histopathological findings in samples from lesions of OLP and leukoplakia with epithelial dysplasia.

Methods

Data for patients with OLP or leukoplakia with moderate or severe epithelial dysplasia recorded during 2006–2011 were retrospectively reviewed. The study samples represented 37 subjects with OLP (n = 14), leukoplakia with moderate (n = 8) or severe (n = 6) epithelial dysplasia, and normal buccal mucosa (controls, n = 9). New sections were subjected to histological examination and immunohistochemistry for Bcl‐2 and Ki‐67 in the basal layer, suprabasal layer, and inflammatory infiltrate, respectively.

Results

All basal layer sections stained either negative or positive in <10% of cells for Bcl‐2 in OLP (92.9% and 7.1%, respectively) and control (77.8% and 22.2%, respectively) samples. In leukoplakia, 85.7% of sections indicated positivity in <10% of cells, and 14.3% indicated positivity in 10–26% of cells. Most OLP (42.9%) and leukoplakia (64.3%) sections stained positive for Ki‐67 in >50% of cells. All suprabasal sections stained either negative or positive in <10% of cells for Bcl‐2 in OLP (92.9% and 7.1%, respectively), leukoplakia (42.9% and 57.1%, respectively), and control (88.9% and 11.1%, respectively) samples. Suprabasal staining for Ki‐67 was negative or positive in <10% of cells in OLP (14.3% and 85.7%, respectively), leukoplakia (7.1% and 92.9%, respectively), and controls (88.9% and 11.1%, respectively). Staining for Bcl‐2 in inflammatory infiltrate in OLP was positive in 92.9% of sections.

Conclusions

Expression of Bcl‐2 may play a dual role in tumor development and progression. Increased cell proliferation in the epithelium may present a predisposition to cancer in OLP. The expression of Ki‐67 can be considered as an adjunct marker for proliferative activity in lesions with malignant potential. The prognostic value of these immunomarkers in the evaluation of precancerous oral lesions requires further investigation.
Review of accessory tragus with highlights of its associated syndromes
Authors: Bahrani Bahar , Khachemoune Amor
Published: September 2014

Accessory tragus is a developmental defect involving malformation of part of the external ear. It is a moderately rare congenital condition reported in 1858 by Birkett for the first time. Histological features of accessory tragus include a thin layer of stratum corneum with a rugated epidermis, presence of eccrine glands, and irregular spatial positioning of vellus hair follicles accompanied by sebaceous glands. Accessory tragus is commonly a limited deformity; however, it can be a sign of associated congenital syndromes. It has been shown to be associated with Goldenhar syndrome, Townes–Brocks syndrome, Treacher‐Collins syndrome, VACTERL syndrome, and Wolf–Hirschhron syndrome. Surgical excision, the most common form of management of accessory tragus lesions, typically leads to a positive outcome. An extensive search was performed using pubmed.gov, Embase, MedLine, and Googlescholar.com using key words: accessory tragus, congenital malformations of ear, first branchial arch, and embryology. In this paper, we review the clinical and histological presentation, associated syndromes, management, and outcome of accessory tragus.
Membrane and soluble Toll‐like receptor 2 in patients with psoriasis treated by Goeckerman therapy
Authors: Kondelkova Katerina , Krejsek Jan , Borska Lenka , Fiala Zdenek , Hamakova Kveta , Ettler Karel , Andrys Ctirad
Published: September 2014

Background

Toll‐like receptor (TLR) 2 belongs to the large TLR receptor family comprised of at least 10 members with different roles in innate immunity. Psoriasis is recognized as a T‐cell driven immune‐mediated systemic inflammatory disease with a skin manifestation. An effective therapeutic approach to treat psoriasis is Goeckerman therapy (GT). The aim of this study was to assess both the kinetics of the expression of TLR2 on blood cells and the concentration of soluble (s)TLR2 in serum of patients with psoriasis and to examine the effect of GT on both TLR2 expression and sTLR2 level.

Methods

Both membrane and sTLR2 were determined in 20 patients and 20 healthy controls. sTLR2 was evaluated by enzyme‐linked immunosorbent assay. Flow cytometry method was used to determine the expression of membrane TLR2 of monocytes and granulocytes.

Results

The serum level of sTLR2 was significantly lower (P < 0.0001) in patients both before and after GT compared to the control group. Compared to the membrane expression of TLR2 on monocytes of healthy blood donors, TLR2 expression was significantly higher in patients both before and after GT (P = 0.0001). Similarly, TLR2 expression on granulocytes was significantly higher in patients both before (P = 0.0061) and after (P < 0.0001) therapy than in control.

Conclusions

Membrane and soluble TLR2 may be involved in the pathogenesis of psoriasis. Both remained unchanged by GT.
Treatment of pseudoepitheliomatous, keratotic, and micaceous balanitis with topical photodynamic therapy
Authors: Zhu Hui , Jiang Yong , Watts Matthew , Kong Fanrong
Published: September 2014

Background

Pseudoepitheliomatous, keratotic, and micaceous balanitis (PKMB) is an extremely rare condition occurring over the glans in older men who undergo circumcision late in life. Its exact etiology is unknown.

Objectives

We report a patient with PKMB that involved the meatus and led to urinary obstruction.

Methods

A 57‐year‐old, circumcised man presented with partial urinary obstruction caused by a thick, nail‐like covering on the skin of his glans penis. Based on histology, PKMB was diagnosed. There was no cytological atypia. The patient was treated successfully with topical 5‐aminolevulinic acid (ALA) photodynamic therapy (PDT).

Results

There was no recurrence after 18 months of follow‐up. Treatment with ALA–PDT seems to be effective and well tolerated in PKMB.

Conclusions

This case indicates that ALA–PDT may be an effective treatment option for plaque‐stage PKMB and thus warrants further investigation.
Microstructure and Electric Properties of CaCu3Ti4O12 Multilayer Capacitors
Authors: Löhnert Romy , Bartsch Heike , Schmidt Rainer , Capraro Beate , Töpfer Jörg
Published: September 2014

In a three‐step development process CaCu3Ti4O12‐based bulk ceramic pellets, tape‐casted multilayer ceramic laminates, and multilayer ceramic capacitors with cofired electrodes were fabricated. The sintering behavior, microstructure, electrical resistivity, and dielectric properties were studied. At a firing temperature of 1050°C, an effective permittivity of about ε′ = 60 000 and 10 000 was observed for sintered pellets and multilayer laminates, respectively. The typical grain growth observed in pellets is suppressed in multilayer laminates. Impedance spectroscopy was employed to show that the bulk grain resistivity is similar in pellets and multilayer laminates, but the grain‐boundary resistivity is higher in pellets. Tapes were processed into multilayer capacitors with Ag/Pd electrodes and cofired at 1050°C. All three types of samples, pellets, laminates, and capacitors were also processed with a glass additive, in which case they can be cofired at a lower temperature of 900°C. In glass‐containing pellets, the temperature dependence of permittivity is weak and exhibits X7R characteristics for frequencies below ≈ 60 kHz. Our results demonstrate the high potential of CaCu3Ti4O12 for application in monolithic as well as in integrated multilayer capacitors.
Measuring Preparedness for Mammography in Women with Intellectual Disabilities: A Validation Study of the Mammography Preparedness Measure
Authors: Wang Claire Tienwey , Greenwood Nechama , White Laura F. , Wilkinson Joanne
Published: September 2014

Background

Women with intellectual disabilities have similar breast cancer rates as the general population, but lower rates of regular mammography and higher breast cancer mortality rates. Although prior qualitative work demonstrates that women with intellectual disabilities face unique, disability‐specific barriers to mammography, the present authors lack standardized, validated instruments for measuring knowledge of breast cancer screening in this population. In addition, much research related to adults with intellectual disabilities focuses on family or carer perspectives, rather than involving women with intellectual disabilities, themselves.

Methods

The present authors first pilot tested a general population instrument measuring breast cancer knowledge, and found that it did not perform adequately in women with intellectual disabilities. In response, the present authors developed the Mammography Preparedness Measure (MPM), a direct short interview tool to measure knowledge and preparedness in women with intellectual disabilities, themselves, rather than relying on caregiver or other reports, and using inclusive methodology. The present authors validated the MPM by assessing test–retest reliability.

Results

Average test–retest per cent agreement of 84%, ranging from 74 to 91% agreement per item, with an overall kappa of 0.59.

Conclusion

The MPM appears to be a valid instrument appropriate for measuring mammography preparedness in women with intellectual disabilities. The success of this innovative tool suggests that direct, rather than informant‐directed tools can be developed to measure health knowledge and cancer screening readiness in adults with intellectual disabilities, an important measure in studying and reducing disparities.
Of peaks and valleys: testing the roles of orogeny and habitat heterogeneity in driving allopatry in mid‐elevation frogs (Aromobatidae: Rheobates) of the northern Andes
Authors: Muñoz‐Ortiz Astrid , Velásquez‐Álvarez Álvaro Andrés , Guarnizo Carlos E. , Crawford Andrew J.
Published: September 2014

Aim

The frog genus Rheobates (Anura: Aromobatidae) is endemic to mid‐elevations in the Colombian Andes. Our aim was to evaluate the role of the northern Andean high peaks and the low Magdalena Valley in creating barriers to dispersal and promoting vicariance within Rheobates.

Location

Three disjunct mid‐elevation flanks of the northern Colombian Andes: the eastern and western flanks of the Eastern Cordillera, separated by high mountain peaks, and the eastern flank of the Central Cordillera, separated from the Eastern Cordillera by the arid Magdalena Valley.

Methods

We analysed mitochondrial and nuclear DNA sequences from 37 individuals of Rheobates to infer their phylogenetic relationships, divergence times and ancestral areas. We used species distribution models to test the role of climatic variables in determining the present geographical boundaries of the species.

Results

The phylogeny of Rheobates is largely predicted by geography, with one population from the eastern flank of the Eastern Cordillera sharing a most recent common ancestor with all other Rheobates 21 million years ago (Ma; 95% credible interval 31–10 Ma). Populations in the Central Cordillera were monophyletic, isolated across the Magdalena Valley with a divergence time estimated at 13 Ma (19–7 Ma). We also detected one recent crossing of the Eastern Cordillera, along with unanticipated latitudinal phylogeographical structure within the western flank of the Eastern Cordillera. Environmental niche tests indicated that the Magdalena Valley and the high peaks of the Eastern Cordillera are significant environmental barriers for Rheobates populations.

Main conclusions

Diversification in Rheobates coincided with the early Miocene uplift of Colombia's Eastern Cordillera and the hypothesized onset of aridity in the Magdalena Valley during the middle Miocene. Our study offers broad support for the classic mountain orogeny model of vicariant divergence, but suggests that lowland habitat heterogeneity also played a long‐term role in promoting vicariance, despite a long history of palaeoclimatic fluctuations.
Mechanotransduction in intervertebral discs
Authors: Tsai Tsung‐Ting , Cheng Chao‐Min , Chen Chien‐Fu , Lai Po‐Liang
Published: September 2014

Mechanotransduction plays a critical role in intracellular functioning—it allows cells to translate external physical forces into internal biochemical activities, thereby affecting processes ranging from proliferation and apoptosis to gene expression and protein synthesis in a complex web of interactions and reactions. Accordingly, aberrant mechanotransduction can either lead to, or be a result of, a variety of diseases or degenerative states. In this review, we provide an overview of mechanotransduction in the context of intervertebral discs, with a focus on the latest methods of investigating mechanotransduction and the most recent findings regarding the means and effects of mechanotransduction in healthy and degenerative discs. We also provide some discussion of potential directions for future research and treatments.
Association of the variants in the PPARG gene and serum lipid levels: a meta‐analysis of 74 studies
Authors: Li Qing , Chen Rong , Bie Lizhan , Zhao Dandan , Huang Chunkai , Hong Jiang
Published: September 2014

Considerable studies have been carried out to investigate the relationship between the polymorphisms of PPARG (Pro12Ala, C161T and C1431T) and serum lipid levels, but the results were inconclusive. Hence, we conducted a meta‐analysis to clarify the association. MEDLINE, EMBASE and the Cochrane Library databases were searched systematically. The subgroup analysis was performed based on ethnicity. Seventy‐four studies with 54,953 subjects were included in this meta‐analysis. In Pro12Ala, the group with the ‘PP’ (C/C genotype) genotype group had lower levels of total cholesterol (TC) (mean difference, MD: −0.02, P < 0.00001; I2 = 28%), low‐density lipoprotein cholesterol (LDL‐C) (MD: −0.02, P < 0.00001; I2 = 30%) and higher levels of triglyceride (TG) (MD: 0.06, P < 0.00001; I2 = 30%) than the combined ‘PA+AA’ (PA = C/G genotype, AA = G/G genotype) genotype group in Asian population, and the group with the ‘PP’ genotype had higher levels of TG (MD: 0.07, P < 0.02; I2 = 67%) than the combined ‘PA+AA’ genotype group in non‐Asian population. No statistically significant differences in the levels of TC, TG, high‐density lipoprotein cholesterol, LDL‐C were detected between different genotypes in C161T(Asian or non‐Asian) and C1431T(Asian) polymorphisms. This meta‐analysis was a renewed and confirmed study to assess the association between PPARG polymorphisms and serum lipid levels in Asian and non‐Asian populations. There is a prominent association between Pro12Ala polymorphism and the levels of TC, LDL‐C and TG in Asian population. No statistically significant differences in serum lipid levels were detected between different genotypes in C161T and C1431T polymorphisms.
Consensus on performing skin biopsies, laboratory workup, evaluation of tissue samples and reporting of the results in patients with suspected cutaneous graft‐versus‐host disease
Authors: Hillen U. , Häusermann P. , Massi D. , Janin A. , Wolff D. , Lawitschka A. , Greinix H. , Meyer R. , Ziemer M.
Published: September 2014

Background

Histopathological diagnosis including selection of lesions, the determination of the best point of time for biopsy and workup is not trivial in cutaneous graft‐versus‐host disease (GvHD).

Objectives

To develop interdisciplinary recommendations on performing, the laboratory work up and reporting of the results of skin biopsies in patients with suspected cutaneous GvHD.

Methods

A working group consisting of dermatopathologists, dermatologists, transplant‐physicians and transplant‐pathologists prepared recommendations for performing skin biopsies, laboratory workup and evaluation of tissue samples, and reporting of the results in patients with cutaneous GvHD. After achieving a consensus within the working group, a survey that comprised the core issues of the recommendations was electronically sent out to 72 alloHSCT centres within Germany, Austria, and Switzerland and their Departments of Pathology. The answers were discussed in a Consensus Conference and final recommendations were established.

Results

Twenty‐five centres responded to the clinical and 17 centres to the histopathological survey. Questions addressed to the clinicians comprised the indication for skin biopsy in chronic GvHD (cGvHD) and acute GvHD (aGvHD) and the appropriate point of time for skin biopsy. Eighty‐eight per cent agreed that the skin biopsy is generally indicated in patients with suspected cGvHD lacking diagnostic features. In contrast, with suspected aGvHD, only 62% of respondents felt that skin biopsy was necessary even if GvHD had not been confirmed in another organ. Although restricted due to the fact that immunosuppression is often applied in an emergency setting most centres supported skin biopsies before initiation of topical or systemic immunosuppression. The majority of pathologists agreed that in non‐sclerotic GvHD a punch biopsy is adequate, whereas in sclerotic GvHD a scalpel biopsy is preferred.

Conclusion

While a consensus on the need for biopsies in cGvHD was reached the value of skin biopsies in aGvHD and subsequent biopsies during therapy requires further evaluation.
An improved Peltier effect‐based instrument for critical temperature threshold measurement in cold‐ and heat‐induced urticaria
Authors: Magerl M. , Abajian M. , Krause K. , Altrichter S. , Siebenhaar F. , Church M.K.
Published: September 2014

Background

Cold‐ and heat‐induced urticaria are chronic physical urticaria conditions in which wheals, angioedema or both are evoked by skin exposure to cold and heat respectively. The diagnostic work up of both conditions should include skin provocation tests and accurate determination of critical temperature thresholds (CTT) for producing symptoms in order to be able to predict the potential risk that each individual patient faces and how this may be ameliorated by therapy.

Objective

To develop and validate TempTest® 4, a simple and relatively inexpensive instrument for the accurate determination of CTT which may be used in clinical practice.

Methods

TempTest® 4 has a single 2 mm wide 350 mm U‐shaped Peltier element generating a temperature gradient from 4 °C to 44 °C along its length. Using a clear plastic guide placed over the skin after provocation, CTT values may be determined with an accuracy of ±1 °C. Here, TempTest® 4 was compared with its much more expensive predecessor, TempTest® 3, in inducing wheals in 30 cold urticaria patients.

Results

Both TempTest® 4 and TempTest® 3 induced wheals in all 30 patients between 8 ° and 28 °C. There was a highly significant (P < 0.0001) correlation between the instruments in the CTT values in individual patients.

Conclusion

The TempTest® 4 is a simple, easy to use, licensed, commercially available and affordable instrument for the determination of CTTs in both cold‐ and heat‐induced urticaria.
Combining propensity score‐based stratification and weighting to improve causal inference in the evaluation of health care interventions
Authors: Linden Ariel
Published: September 2014

When a randomized controlled trial is not feasible, a key strategy in observational studies is to ensure that intervention and control groups are comparable on observed characteristics and assume that the remaining unmeasured characteristics will not bias the results. In the past few years, propensity score‐based techniques such as matching, stratification and weighting have become increasingly popular for evaluating health care interventions. Recently, marginal mean weighting through stratification (MMWS) has been introduced as a flexible pre‐processing approach that combines the salient features of propensity score stratification and weighting to remove imbalances of pre‐intervention characteristics between two or more groups under study. The weight is then used within the appropriate outcome model to provide unbiased estimates of treatment effects. In this paper, the MMWS technique is introduced by illustrating its implementation in three typical experimental conditions: a binary treatment (treatment versus control), an ordinal level treatment (varying doses) and nominal treatments (multiple independent arms). These methods are demonstrated in the context of health care evaluations by examining the pre‐post difference in hospitalizations following the implementation of a disease management program for patients with congestive heart failure. Because of the flexibility and wide application of MMWS, it should be considered as an alternative procedure for use with observational data to evaluate the effectiveness of health care interventions.
Interpreting zirconium‐in‐rutile thermometric results
Authors: Taylor‐Jones K. , Powell R.
Published: September 2014

At first sight, experimental results and observations on rocks suggest that the Zr content in rutile, where equilibrated with quartz and zircon, should be a useful thermometer for metamorphic rocks. However, diffusion data for Zr in rutile imply that thermometry should not, for plausible rates of cooling, give the high temperatures commonly observed in high‐grade metamorphic rocks. It is suggested here that such observations can be accounted for by high‐T diffusive closure of Si in rutile, causing the interior of rutile grains to become insensitive to the thermometer equilibrium well above the temperature of Zr diffusive closure. Paired with comparatively slow grain boundary diffusion and problematic zircon nucleation, this allows for cases of Zr retention in rutile through temperatures where Zr is still diffusively mobile within rutile grains. Other observations that may be accounted for in this context are large inter‐grain ranges of rutile Zr contents uncorrelated with rutile grain size, and flat Zr profiles across individual rutile grains, counter to what would be expected from diffusive closure. A consequence is that it is unlikely that Zr‐in‐rutile thermometry will be useful for estimating rock cooling rates.
Childhood nephrotic syndrome in the 21st century: What's new?
Authors: Metz David Kieran , Kausman Joshua Yehuda
Published: September 2014

Childhood nephrotic syndrome is a condition managed by general paediatricians and paediatric nephrologists. Whether treating a first presentation or a relapse, the clinician requires expertise in order to minimise the risk of serious complications and optimise long‐term care. Indeed, many children suffer a difficult relapsing course in their disease, warranting consideration of second‐line therapies. The last two decades have witnessed a growing knowledge of the condition and increased complexity of diagnostic and therapeutic options, which poses a challenge for the general paediatrician, given the condition's relative rarity in daily practice. This review aims to familiarise the reader with some of the most important recent developments and particularly to provide an insight into what management options are available and when it may be appropriate to seek advice from a nephrologist.
Effect of GABA on oxidative stress in the skeletal muscles and plasma free amino acids in mice fed high‐fat diet
Authors: Xie Z.X. , Xia S.F. , Qiao Y. , Shi Y.H. , Le G.W.
Published: September 2014

Increased levels of plasma free amino acids (pFAAs) can disturb the blood glucose levels in patients with obesity, diabetes mellitus and metabolic syndrome (MS) and are associated with enhanced protein oxidation. Oxidation of proteins, especially in the muscles, can promote protein degradation and elevate the levels of pFAAs. Gamma‐aminobutyric acid (GABA), a food additive, can reduce high‐fat diet (HFD)‐induced hyperglycaemia; however, the mechanisms remain unclear. The aim of this study was to evaluate the effects of GABA on protein oxidation and pFAAs changes. One hundred male C57BL/6 mice were randomly divided into five groups that were fed with control diet, HFD and HFD supplied with 0.2%, 0.12% and 0.06% GABA in drinking water for 20 weeks respectively. HFD feeding led to muscular oxidative stress, protein oxidation, pFAA disorders, hyperglycaemia and augmented plasma GABA levels. Treatment with GABA restored normally fasting blood glucose level and dose‐dependently inhibited body weight gains, muscular oxidation and protein degradation. While medium and low doses of GABA mitigated HFD‐induced pFAA disorders, the high dose of GABA deteriorated the pFAA disorders. Medium dose of GABA increased the levels of GABA, but high dose of GABA reduced the levels of plasma GABA and increased the activity of succinic semialdehyde dehydrogenase in the liver. Therefore, treatment with GABA mitigated HFD‐induced hyperglycaemia probably by repairing HFD‐induced muscular oxidative stress and pFAA disorders in mice. Our data also suggest that an optimal dose of GABA is crucial for the prevention of excess GABA‐related decrease in the levels of pFAA and GABA as well as obesity.
Interleukin‐33 could play an important role in the pathogenesis of periodontitis
Authors: Köseoğlu S. , Hatipoğlu M. , Sağlam M. , Enhoş Ş. , Esen H. H.
Published: September 2014

Background and Objective

Interleukin‐33 (IL‐33) controls T‐helper type 2 (Th2) cytokines and the development of mast cells. This study aimed to investigate the expression of IL‐33 and its association with RANKL and osteoprotegerin (OPG) in periodontal health and experimental periodontitis.

Material and Methods

Eighteen Wistar rats were assigned to two study groups of nine animals each: ligature only (LO) and nonligated (NL). Silk sutures were placed subgingivally, surrounding the right lower first molars. The animals were killed on day 11 after ligature placement, and the alveolar bone loss at the first molars was determined histometrically. Periodontal tissues were examined histopathologically to evaluate the differences between the groups. The expression of IL‐33, RANKL and OPG was detected immunohistochemically.

Results

The LO group showed significantly greater alveolar bone loss compared with the NL group (p < 0.05). The numbers of osteoclasts, osteoblasts and inflammatory cells were significantly higher in the LO group compared with the NL group (p < 0.05). Osteoblastic activity was significantly lower in the LO group than in the NL group (p < 0.05). There was significantly higher expression of IL‐33 and RANKL and a greater number of OPG‐positive cells in the LO group (p < 0.05). IL‐33 expression showed a positive correlation with RANKL expression and with the number of mast cells (p < 0.05).

Conclusion

The experimental periodontitis group exhibited increased expression of IL‐33 and RANKL compared with the healthy group. Additionally, there was a positive correlation between these expressions. According to these results, IL‐33 could be associated with the pathogenesis of periodontal disease.
Wireless Ambulatory Esophageal pH Monitoring in Dogs with Clinical Signs Interpreted as Gastroesophageal Reflux
Authors: Kook P.H. , Kempf J. , Ruetten M. , Reusch C.E.
Published: September 2014

Background

Although gastroesophageal reflux (GER) often is assumed to be causative for upper gastrointestinal and respiratory signs in dogs, no attempts have been made to verify this assumption.

Objectives

To monitor esophageal pH with the Bravo pH system in healthy dogs and client‐owned dogs displaying signs commonly attributed to GER.

Animals

Seven healthy and 22 client‐owned dogs.

Methods

After routine esophagogastroduodenoscopy, radiotelemetric pH capsules were placed in distal esophagus for continuous pH recording. Reflux was defined as single pH measurement <4. At discharge, owners were instructed to press individually predefined clinical sign‐buttons on the receiver whenever indicated. Results between groups were compared using Mann–Whitney U‐test.

Results

The median (range) number of refluxes in client‐owned and healthy dogs, respectively, was 17 (1–205) and 10 (1–65), the number of refluxes >5 minutes in duration was 1 (0–14), and 1 (0–4), duration of longest reflux (min) was 10 (0–65) and 8 (0–27), and fractional time pH <4 (%) was 0.76% (0.01–6.28), and 0.3% (0–3.1). No differences were found between groups. The median of 7 (1–35) clinical sign‐button pushes were recorded in 21 dogs. Median of 12.5% (2.8% [1/35]–50% [2/4]) reflux‐positive clinical sign‐button pushes was found in 10 dogs with reflux‐positive pushes. Five (22.7%) dogs had increased esophageal acid exposure, and mild esophagitis was noted in 1 dog.

Conclusion and Clinical Importance

Despite evidence of increased GER in some dogs, the clinical sign‐reflux association remained poor. Future investigation should focus on dogs with esophagitis.
A comparison of key aspects of gene regulation in Streptomyces coelicolor and Escherichia coli using nucleotide‐resolution transcription maps produced in parallel by global and differential RNA sequencing
Authors: Romero David A. , Hasan Ayad H. , Lin Yu‐fei , Kime Louise , Ruiz‐Larrabeiti Olatz , Urem Mia , Bucca Giselda , Mamanova Lira , Laing Emma E. , van Wezel Gilles P. , Smith Colin P. , Kaberdin Vladimir R. , McDowall Kenneth J.
Published: September 2014

Streptomyces coelicolor is a model for studying bacteria renowned as the foremost source of natural products used clinically. Post‐genomic studies have revealed complex patterns of gene expression and links to growth, morphological development and individual genes. However, the underlying regulation remains largely obscure, but undoubtedly involves steps after transcription initiation. Here we identify sites involved in RNA processing and degradation as well as transcription within a nucleotide‐resolution map of the transcriptional landscape. This was achieved by combining RNA‐sequencing approaches suited to the analysis of GC‐rich organisms. Escherichia coli was analysed in parallel to validate the methodology and allow comparison. Previously, sites of RNA processing and degradation had not been mapped on a transcriptome‐wide scale for E. coli. Through examples, we show the value of our approach and data sets. This includes the identification of new layers of transcriptional complexity associated with several key regulators of secondary metabolism and morphological development in S. coelicolor and the identification of host‐encoded leaderless mRNA and rRNA processing associated with the generation of specialized ribosomes in E. coli. New regulatory small RNAs were identified for both organisms. Overall the results illustrate the diversity in mechanisms used by different bacterial groups to facilitate and regulate gene expression.
A Caulobacter MreB mutant with irregular cell shape exhibits compensatory widening to maintain a preferred surface area to volume ratio
Authors: Harris Leigh K. , Dye Natalie A. , Theriot Julie A.
Published: September 2014

Rod‐shaped bacteria typically elongate at a uniform width. To investigate the genetic and physiological determinants involved in this process, we studied a mutation in the morphogenetic protein MreB in Caulobacter crescentus that gives rise to cells with a variable‐width phenotype, where cells have regions that are both thinner and wider than wild‐type. During growth, individual cells develop a balance of wide and thin regions, and mutant MreB dynamically localizes to poles and thin regions. Surprisingly, the surface area to volume ratio of these irregularly shaped cells is, on average, very similar to wild‐type. We propose that, while mutant MreB localizes to thin regions and promotes rod‐like growth there, wide regions develop as a compensatory mechanism, allowing cells to maintain a wild‐type‐like surface area to volume ratio. To support this model, we have shown that cell widening is abrogated in growth conditions that promote higher surface area to volume ratios, and we have observed individual cells with high ratios return to wild‐type levels over several hours by developing wide regions, suggesting that compensation can take place at the level of individual cells.
Species boundaries and nomenclature of Rhizopus arrhizus (syn. R. oryzae)
Authors: Dolatabadi Somayeh , de Hoog G. Sybren , Meis Jacques F. , Walther Grit
Published: September 2014

Rhizopus arrhizus (Mucorales, Mucoromycotina) is the prevalent opportunist worldwide among the mucoralean species causing human infections. On the other hand the species has been used since ancient times to ferment African and Asian traditional foods and condiments based on ground soybeans. As producer of organic acids and hydrolytic enzymes it is widely applied in food industry and biotechnology. Using a set of 82 strains we studied phylogenetic and biological species boundaries within Rhizopus arrhizus s.l. to test the taxonomic status of R. delemar that was recently separated from R. arrhizus. Sequence analyses based on the internal transcribed spacer region, the gene of the largest subunit of the RNA polymerase II, a part of the actin gene, and the translation elongation factor 1‐α as well as amplified fragment length polymorphism analysis were performed. Phenotypic characters such as enzyme profiles and growth kinetics were examined and the mating behavior was tested. Molecular analyses supported the existence of two phylogenetic species. However, the results of the mating test suggest that the mating barrier is still not complete. No physiological, ecological or epidemiological distinction could be found beside the difference in the production of organic acids. Consequently the status of varieties is proposed for the two phylogenetic species. Because the description of the first described R. arrhizus is considered to be conclusive we recommend the use of Rhizopus arrhizus var. arrhizus and var. delemar.
Multiple environmental changes interact to modify species dynamics and invasion rates
Authors: Griffiths Jason I. , Warren Philip H. , Childs Dylan Z.
Published: September 2014

Multiple aspects of the environment often change at the same time, influencing populations directly by modifying their physiology, but also indirectly by influencing other interacting species. The impacts of each environmental change upon population dynamics are usually assumed be independent of the state of other aspects of the environment, despite evidence at the individual level indicating that the combined impacts are often non‐additive. The importance of indirect effects mediated through community interactions also has high uncertainty. We used experimental microcosms to determine whether environmental factors interact to affect species dynamics and the relative importance of direct and indirect effects on species dynamics.

We factorially manipulated three aspects of the environment (temperature, food availability and salinity) and examined reciprocal invasions of competing protist species under each environment. Experimental observations were used to parameterize a dynamic model of the system. Using this model and a novel variance decomposition method, we examined the mechanisms by which environmental changes altered species invasion rates.

The three environmental factors interacted when modifying species growth rates, intra‐ and interspecific competition, causing the impact of each environmental change on species dynamics to depend crucially on the state of other aspects of the environment. Indirect changes in the abundance of the resident competitor and its interspecific competitive ability were the main cause of environmental driven variation in invasion rates, whilst direct effects on species intrinsic growth rates were relatively unimportant. This indicates that, to understand and ultimately predict species and community responses to multiple environmental changes, we should consider their joint impacts and the mechanisms by which they interact to modify key ecological processes such as competition.
Evaluation of the minimum volume of salvage blood required for the successful use of two different autotransfusion devices
Authors: Baumann Cyrille , Lamesic Goran , Weiss Markus , Cushing Melissa M. , Haas Thorsten
Published: September 2014

Background

Autotransfusion in pediatric anesthesia is beneficial in several clinical settings; however, more frequent usage is deterred by process‐related costs and the fact that the absolute volume of blood returned may be minimal.

Objective

Two autotransfusion devices (CATS, Fresenius Kabi AG, and Sorin Xtra, Sorin GmbH) with different technologies were evaluated to determine the minimum volume necessary to efficiently process salvage blood.

Methods

Banked blood was diluted to simulate different clinical scenarios. Volume and red cell mass in returned blood were analyzed as a function of initial volume and red cell mass in the collection reservoir using incremental increases in the volume of blood added to the reservoir.

Results

The volume of the returned processed blood for infusion was dependent on degree of dilution and blood volume in the reservoir. The CATS required a smaller initial minimum volume to process and successfully return; however, the Xtra provided a more efficient recovery at low initial collected volumes. Using test blood of various degrees of dilution, the CATS and Xtra were able to return blood for retransfusion after a mean initial red cell mass of 48.7 ml (±4.9 ml) and 53.7 ml (±5.0 ml) were processed, respectively.

Conclusions

Red cell mass rather than salvaged blood volume represents a reliable predictor of the successful use of an autotransfusion device. Measuring the hematocrit of the salvaged blood could improve the use of the devices. The investigated devices are likely to be roughly equivalent in effectiveness.