bluuebunny/crossref_metadata_2025 huggingface dataset:
MAL facilitates the incorporation of exocytic uroplakin-delivering vesicles into the apical membrane of urothelial umbrella cells
Authors: Zhou Ge , Liang Feng-Xia , Romih Rok , Wang Zefang , Liao Yi , Ghiso Jorge , Luque-Garcia Jose L. , Neubert Thomas A. , Kreibich Gert , Alonso Miguel A. , Schaeren-Wiemers Nicole , Sun Tung-Tien
Published: February 2012

The apical surface of mammalian bladder urothelium is covered by large (500–1000 nm) two-dimensional (2D) crystals of hexagonally packed 16-nm uroplakin particles (urothelial plaques), which play a role in permeability barrier function and uropathogenic bacterial binding. How the uroplakin proteins are delivered to the luminal surface is unknown. We show here that myelin-and-lymphocyte protein (MAL), a 17-kDa tetraspan protein suggested to be important for the apical sorting of membrane proteins, is coexpressed with uroplakins in differentiated urothelial cell layers. MAL depletion in Madin–Darby canine kidney cells did not affect, however, the apical sorting of uroplakins, but it decreased the rate by which uroplakins were inserted into the apical surface. Moreover, MAL knockout in vivo led to the accumulation of fusiform vesicles in mouse urothelial superficial umbrella cells, whereas MAL transgenic overexpression in vivo led to enhanced exocytosis and compensatory endocytosis, resulting in the accumulation of the uroplakin-degrading multivesicular bodies. Finally, although MAL and uroplakins cofloat in detergent-resistant raft fractions, they are associated with distinct plaque and hinge membrane subdomains, respectively. These data suggest a model in which 1) MAL does not play a role in the apical sorting of uroplakins; 2) the propensity of uroplakins to polymerize forming 16-nm particles and later large 2D crystals that behave as detergent-resistant (giant) rafts may drive their apical targeting; 3) the exclusion of MAL from the expanding 2D crystals of uroplakins explains the selective association of MAL with the hinge areas in the uroplakin-delivering fusiform vesicles, as well as at the apical surface; and 4) the hinge-associated MAL may play a role in facilitating the incorporation of the exocytic uroplakin vesicles into the corresponding hinge areas of the urothelial apical surface.
An Injectable Adipose Matrix for Soft-Tissue Reconstruction
Authors: Wu Iwen , Nahas Zayna , Kimmerling Kelly A. , Rosson Gedge D. , Elisseeff Jennifer H.
Published: February 2012

Background:

Soft-tissue repair is currently limited by the availability of autologous tissue sources and the absence of an ideal soft-tissue replacement comparable to native adipose tissue. Extracellular matrix–based biomaterials have demonstrated great potential as instructive scaffolds for regenerative medicine, mechanically and biochemically defined by the tissue of origin. As such, the distinctive high lipid content of adipose tissue requires unique processing conditions to generate a biocompatible scaffold for soft-tissue repair.

Methods:

Human adipose tissue was decellularized to obtain a matrix devoid of lipids and cells while preserving extracellular matrix architecture and bioactivity. To control degradation and volume persistence, the scaffold was cross-linked using hexamethylene diisocyanate and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide. In vitro studies with human adipose-derived stem cells were used to assess cell viability and adipogenic differentiation on the biomaterial. In vivo biocompatibility and volume persistence were evaluated by subcutaneous implantation over 12 weeks in a small-animal model.

Results:

The scaffold provided a biocompatible matrix supporting the growth and differentiation of adipose-derived stem cells in vitro. Cross-linking the matrix increased its resistance to enzymatic degradation. Subcutaneous implantation of the acellular adipose matrix in Sprague-Dawley rats showed minimal inflammatory reaction. Adipose tissue development and vascularization were observed in the implant, with host cells migrating into the matrix indicating the instructive potential of the matrix for guiding tissue remodeling and regeneration.

Conclusions:

With its unique biological and mechanical properties, decellularized adipose extracellular matrix is a promising biomaterial scaffold that can potentially be used allogenically for the correction of soft-tissue defects.
Prophylactic Muscle Flaps in Vascular Surgery
Authors: Fischer John P. , Nelson Jonas A. , Rohrbach Jeff I. , Wu Liza C. , Woo Edward Y. , Kovach Stephen J. , Low David W. , Serletti Joseph M. , Kanchwala Suhail
Published: February 2012

Background:

High-risk patients undergoing vascular procedures through inguinal incisions experience significant benefit from undergoing prophylactic muscle flaps. The authors present a risk assessment tool, an evidence-based algorithm for using prophylactic muscle flaps, and a comprehensive cost analysis.

Methods:

Data derived from the authors' previously performed retrospective cohort study of patients undergoing open vascular groin surgery were used to construct an evidence-based risk assessment tool. A multivariate regression analysis identified significant, independent predictors of complications, which were used to construct a scoring system. An institutional cost analysis and preoperative assessment algorithm were derived based on patient risk stratification and statistical analyses.

Results:

Sixty-eight prophylactic flaps in 53 patients were compared with 195 open femoral access procedures without flaps in 178 patients. Multivariate regression demonstrated that obesity, smoking, reoperation, and prosthetic graft reconstruction are significant predictors of complications. A weighted risk factor score (0 to 7) was devised: obesity, for a value of 1; smoking, 2; reoperation for open groin surgery, 2; and prosthetic graft material, 2. Patients with higher scores had significantly more complications, infections, and more frequently required secondary salvage flap procedures. Using study data, the authors constructed an algorithm to guide preoperative groin assessment and use of prophylactic muscle flaps.

Conclusions:

The authors provide an assessment tool, called the Penn Groin Assessment Scale, that accurately predicts groin complications. They also describe a simple algorithm to assess for prophylactic muscle coverage. Their results suggest that patients with two or more risk factors will benefit from prophylactic muscle flaps.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, II.
Gender, Culture and Intervention: Exploring Differences between Aboriginal and Non‐Aboriginal Children’s Responses to an Early Intervention Programme
Authors: Robinson Gary W. , Tyler William B. , Silburn Sven R. , Zubrick Stephen R.
Published: February 2012

Evaluation of a group parenting programme in the Northern Territory of Australia showed significant differences in benefits for Aboriginal and non‐Aboriginal boys and girls. The analysis considers whether boys and girls from different cultural backgrounds present with different problems; whether parental expectations for boys and girls differ and whether the intervention activates different responses in different settings. Conclusions suggest that there is a need to closely examine the ‘cultural logic’ of interventions, the appropriateness of their assumptions about child development and hypothesised mechanisms of change in different settings.
Soil CO2 concentration and efflux as affected by heavy traffic in forest in northeast France
Authors: Goutal N. , Parent F. , Bonnaud P. , Demaison J. , Nourrisson G. , Epron D. , Ranger J.
Published: February 2012

An experimental site was set up in northeast France on a Luvisol (ruptic) soil to examine the duration of physical, chemical and biological disturbances in the soil following mechanized forest harvesting. Soil carbon dioxide (CO2) efflux (SE) and concentration ([CO2]) in the silt loam layer (0–50 cm) were measured from March 2008 to March 2010 in the trafficked (T) and control (C) plots of this site. This study aimed to validate these two measurements as indicators for long‐term soil monitoring following disturbance by heavy traffic in 2007. Throughout the sampling period, SE in the T‐treatment was significantly reduced relative to that in the C‐treatment. The response of [CO2] to traffic depended on the season; it decreased during summer and increased during winter and spring. The combination of the two measurements indicated an increase in the frequency and duration of anoxic conditions resulting from poor gas diffusion after heavy forest traffic. The relationships between soil climatic properties (temperature, water content and water table level) on one hand and SE or [CO2] on the other, demonstrated a strong control of SE by soil biological activity and a double control of [CO2] by gas production/consumption and gas transfer. Our findings suggest that [CO2] and SE are sensitive to soil degradation by forest harvesting and that the impact of soil compaction provides complementary information on the processes involved in regulating CO2 production and efflux. However, their use as simple indicators is questionable as the impact varied with time and was probably dependent on the soil type.
A cost‐minimization analysis of root canal treatment before and after education in nickel–titanium rotary technique in general practice
Authors: Koch M. , Tegelberg Å. , Eckerlund I. , Axelsson S.
Published: February 2012

Koch M, Tegelberg Å, Eckerlund I, Axelsson S.A cost‐minimization analysis (CMA) of root canal treatment before and after education in nickel–titanium rotary technique in general practice.International Endodontic Journal,45, 633–641, 2012.

Aim To compare root canal treatments performed before and after education in a nickel–titanium rotary technique (NiTiR) with respect to costs for instrumentation and number of instrumentation sessions in a County Public Dental Service in Sweden.

Methodology Following education, 77% of the general dental practitioners adopted completely the NiTiR. The randomly selected sample comprised 850 root canal treatments: 425 performed after the education, mainly using the NiTiR‐technique (group A) and 425 performed before, using mainly stainless steel hand instrumentation (SSI) (group B). The number of instrumentation sessions in root canal treatments in group A and B was calculated. A CMA was undertaken on the assumption that treatment outcome was identical in group A and B. Direct costs associated with SSI and NiTiR were estimated and compared. Investment costs required for implementation of NiTiR were calculated, but not included in the CMA.

Results Instrumentation sessions were counted in 418 (98%) root canal treatments performed in group A and 419 (99%) in group B. The number of instrumentation sessions in group A was significantly lower; 2.38, compared with 2.82 in group B (P < 0.001). Thus, on average, for every second root canal treatment performed after the education, one instrumentation session was saved. Root canal treatments in teeth with one canal, and three or more canals, were completed in significantly fewer instrumentation sessions after the education (P < 0.001). Direct costs of instrumentation sessions were SEK 2587 (USD 411) for group A and SEK 2851 (USD 453) for group B, for teeth with one canal, and SEK 2946 (USD 468) for group A and SEK 3510 (USD 558) for group B, for teeth with three or more canals (year 2011). Root canal treatments of teeth with two canals showed no significant difference with respect to number of instrumentation sessions and costs.

Conclusions Significantly fewer instrumentation sessions were required in group A, and root canal instrumentation therefore costs less than in group B. On the assumption that treatment outcome is identical in group A and B, root canal instrumentation performed after the education was more cost‐effective.
Life histories have a history: effects of past and present conditions on adult somatic growth rates in wild Trinidadian guppies
Authors: Auer Sonya K. , Lopez‐Sepulcre Andrés , Heatherly Thomas , Kohler Tyler J. , Bassar Ronald D. , Thomas Steven A. , Reznick David N.
Published: February 2012

1. Environmental conditions in the present, more recent past and during the juvenile stage can have significant effects on adult performance and population dynamics, but their relative importance and potential interactions remain unexplored.

2. We examined the influence of food availability at the time of sampling, 2 months prior and during the juvenile stage on adult somatic growth rates in wild Trinidadian guppies (Poecilia reticulata).

3. We found that food availability during both the early and later parts of an individual’s ontogeny had important consequences for adult growth strategies, but the direction of these effects differed among life stages and their magnitude, in some cases, depended on food levels experienced during other life stages. Current food levels and those 2 months prior to growth measurements had positive effects on adult growth rate; though, food levels 2 months prior had a greater effect on growth than current food levels. In contrast, the effects of food availability during the juvenile stage were higher in magnitude but opposite in direction to current food levels and those 2 months prior to growth rate measurements. Individuals recruiting under low food levels grew faster as adults than individuals recruiting during periods of high food availability. There was also a positive interaction between food levels experienced during the juvenile stage and 2 months prior such that the effects of juvenile food level diminished as the food level experienced 2 months prior increased.

4. These results suggest that the similar conditions occurring at different life stages can have different effects on short‐ and long‐term growth strategies of individuals within a population. They also demonstrate that, while juvenile conditions can have lasting effects on adult performance, the strength of that effect can be dampened by environmental conditions experienced as an adult.

5. A simultaneous consideration of past events in both the adult and juvenile stage may therefore improve predictions for individual‐ and population‐level responses to environmental change.
Heavy metal stress can prime for herbivore‐induced plant volatile emission
Authors: WINTER THORSTEN R. , BORKOWSKI LENA , ZEIER JÜRGEN , ROSTÁS MICHAEL
Published: February 2012

Heavy metals are important pollutants that can severely impact ecological foodwebs. In addition to direct toxic effects, these contaminants have been suggested to disrupt chemical communication channels between plants and insects that rely on volatile organic compounds (VOCs). We investigated how different concentrations of copper (Cu) and cadmium (Cd) stress affect the capacity of Zea mays to synthesize VOCs in the presence and absence of herbivorous insects. Hydroponically grown maize exposed to a high and low concentration of either Cu or Cd showed stunted growth and lower photosynthetic capacities. Herbivores feeding on stressed plants also had attenuated growth rates. Heavy metal treatment alone did not induce VOC emission in maize plants; however, the higher Cu dose was found to prime for enhanced volatile production that can be triggered by caterpillar feeding. Cu stress correlated with increased levels of reactive oxygen species in roots and priming of herbivore‐induced jasmonic acid in leaves. Plants challenged with Cd and herbivory did not differ in responses compared with herbivore‐damaged controls with no heavy metals added to the substrate. For Cu stress, our results support the ‘single biochemical mechanism for multiple stressors’ model which predicts overlapping signalling and responses to abiotic and biotic stress factors.
Metabolome analysis of photosynthesis and the related primary metabolites in the leaves of transgenic rice plants with increased or decreased Rubisco content
Authors: SUZUKI YUJI , FUJIMORI TAMAKI , KANNO KEIICHI , SASAKI ATSUSHI , OHASHI YOSHIAKI , MAKINO AMANE
Published: February 2012

Because the comprehensive effects on metabolism by genetic manipulation of leaf Rubisco content are unknown, metabolome analysis was carried out on transgenic rice plants with increased or decreased Rubisco content using the capillary electrophoresis‐time‐of‐flight mass spectrometry (CE‐TOFMS) technique. In RBCS‐sense plants, an increase in Rubisco content did not improve light‐saturated photosynthesis. Glyceraldehyde 3‐phosphate and sedoheputulose 7‐phosphate levels increased, but ribulose bisphosphate (RuBP), ATP and ADP levels were not affected. It is considered from these results that RuBP regeneration independent of ATP supply became a bottleneck for photosynthesis. In RBCS‐antisense plants, a decline in Rubisco content decreased photosynthesis with a substantial accumulation of RuBP. ATP and ADP levels also increased and were associated with increases in the diphosphate and triphosphate compounds of other nucleosides. These results imply that a decline in Rubisco content slowed down the Calvin cycle and that the resultant excess energy of ATP was transferred to other nucleoside diphosphates and triphosphates. The levels of amino acids tended to decline in RBCS‐sense plants and increase in RBCS‐antisense plants, probably reflecting the demand for Rubisco synthesis. Starch and carbohydrate levels decreased only in RBCS‐antisense plants. Thus, genetic manipulation of Rubisco contents widely affected C and N metabolism in rice.
Comparative Analysis of Spontaneous and Mycobacterial Antigen‐Induced Secretion of Th1, Th2 and Pro‐Inflammatory Cytokines by Peripheral Blood Mononuclear Cells of Tuberculosis Patients
Authors: Al‐Attiyah R. , El‐Shazly A. , Mustafa A. S.
Published: February 2012

The cytokines produced by T helper (Th)1 cells (IFN‐γ, IL‐2 and TNF‐β) correlate with protection, whereas the cytokines released by Th2 cells (IL‐4, IL‐5) and the anti‐inflammatory cytokine IL‐10 correlate with pathogenesis of tuberculosis (TB). However, the pro‐inflammatory cytokines (IL‐1β, IL‐6, IL‐8, TNF‐α and IL‐12p70) are responsible for both protection and pathogenesis of TB. The aim of this work was to carry out a comparative analysis of cytokines present in early (day 2) and late (day 6) cultures of peripheral blood mononuclear cells (PBMCs) obtained from pulmonary tuberculosis patients. PBMCs were cultured in vitro in the absence and presence of exogenously added complex mycobacterial antigens and RD1 peptide pool. The supernatants were collected on day 2 and day 6 of culture and assayed for secreted cytokines using the flow cytomix assay. All of the cytokines, except for IL‐12p70, were spontaneously secreted by PBMCs of 27–100% TB patients, but only TNF‐α concentration was significantly higher on day 2 than day 6 (P < 0.05). Two days following antigenic stimulation, only IL‐1β, IL‐6, TNF‐α and IL‐10 were secreted in response to some mycobacterial antigens. However, 6 days later, all of the cytokines, except for IL‐2, IL‐4, IL‐5 and IL‐8, were secreted significantly in response to all complex antigens and RD1 peptides, compared with the non‐stimulated cultures (P < 0.05). In conclusion, the study shows that the longer in vitro stimulation time (6 days) was necessary for the optimal induction of IFN‐γ and TNF‐β, and practically convenient for the detection of IL‐10, IL‐1 β, TNF‐α and IL‐6.
PLP1 duplication at the breakpoint regions of an apparently balanced t(X;22) translocation causes Pelizaeus–Merzbacher disease in a girl
Authors: Fonseca ACS , Bonaldi A , Costa SS , Freitas MR , Kok F , Vianna‐Morgante AM
Published: February 2012

Fonseca ACS, Bonaldi A, Costa SS, Freitas MR, Kok F, Vianna‐Morgante AM. PLP1 duplication at the breakpoint regions of an apparently balanced t(X;22) translocation causes Pelizaeus–Merzbacher disease in a girl.

PLP1 (proteolipid protein1 gene) mutations cause Pelizaeus–Merzbacher disease (PMD), characterized by hypomyelination of the central nervous system, and affecting almost exclusively males. We report on a girl with classical PMD who carries an apparently balanced translocation t(X;22)(q22;q13). By applying array‐based comparative genomic hybridization (a‐CGH), we detected duplications at 22q13 and Xq22, encompassing 487–546 kb and 543–611 kb, respectively. The additional copies were mapped by fluorescent in situ hybridization to the breakpoint regions, on the derivative X chromosome (22q13 duplicated segment) and on the derivative 22 chromosome (Xq22 duplicated segment). One of the 14 duplicated X‐chromosome genes was PLP1.The normal X chromosome was the inactive one in the majority of peripheral blood leukocytes, a pattern of inactivation that makes cells functionally balanced for the translocated segments. However, a copy of the PLP1 gene on the derivative chromosome 22, in addition to those on the X and der(X) chromosomes, resulted in two active copies of the gene, irrespective of the X‐inactivation pattern, thus causing PMD. This t(X;22) is the first constitutional human apparently balanced translocation with duplications from both involved chromosomes detected at the breakpoint regions.
Age‐specific incidence rates for breast cancer in carriers of BRCA1 mutations from Norway
Authors: Møller P , Mæhle L , Vabø A , Clark N , Sun P , Narod SA
Published: February 2012

Møller P, Mæhle L, Vabø A, Clark N, Sun P, Narod SA. Age‐specific incidence rates for breast cancer in carriers of BRCA1 mutations from Norway.

Incidence rates of breast cancer among women with a BRCA1 mutation vary according to their reproductive histories and country of residence. To measure cancer incidence, it is best to follow‐up cohort of healthy women prospectively. We followed up a cohort of 675 women with a BRCA1 mutation who did not have breast or ovarian cancer before inclusion and who had a normal clinical examination and mammography at first visit. After a mean of 7.1 years, 98 incident cases of breast cancer were recorded in the cohort. Annual cancer incidence rates were calculated, and based on these, a penetrance curve was constructed. The average annual cancer risk for the Norwegian women from age 25 to 70 was 2.0%. Founder mutations had lower incidence rate (1.7%) than less frequent mutations (2.5%) (p = 0.03). The peak incidence (3.1% annual risk) was observed in women from age 50 to 59. The age‐specific annual incidence rates and penetrance estimate were compared with published figures for women from North America and from Poland. The risk of breast cancer to age 70 was estimated to be 61% for women from Norway, compared with 55% for women from Poland and 69% for women from North America.
Factors related to immunosuppressant medication adherence in renal transplant recipients
Authors: Chisholm‐Burns Marie , Pinsky Brett , Parker Gretchen , Johnson Phaedra , Arcona Steven , Buzinec Paul , Chakravarti Paula , Good Meg , Cooper Matthew
Published: February 2012

Chisholm‐Burns M, Pinsky B, Parker G, Johnson P, Arcona S, Buzinec P, Chakravarti P, Good M, Cooper M. Factors related to immunosuppressant medication adherence in renal transplant recipients.

Abstract:  Non‐adherence to immunosuppressant medications (ISM) is a significant issue for transplant recipients. This study examines factors influencing ISM adherence in renal transplant recipients (RTRs). Patient‐reported data were collected through a cross‐sectional survey including use of ISMs, adherence behaviors, perceived adherence barriers, beliefs and attitudes toward ISMs, and patient life satisfaction. Logistic regression was conducted to examine how RTRs’ beliefs about use of ISMs, life satisfaction, and ISM adherence barriers were related to adherence. A total of 512 adult commercial insurance enrollees following renal transplantation were included in the analysis. One hundred and seventy‐seven RTRs were non‐adherent (34.5%); the most frequently cited reason was forgetfulness. RTRs aged 18–29 yr were more likely to be non‐adherent than recipients 46–64 yr old (p ≤ 0.001). Non‐adherent RTRs had greater adherence barriers than adherent RTRs (p < 0.001). Adherent RTRs believed their ISMs were more necessary than non‐adherent RTRs (p < 0.001), while non‐adherent RTRs had greater concerns about taking ISMs (p = 0.009) and believed they had less control over their lives than adherent RTRs (p < 0.001). Non‐adherent RTRs had lower life satisfaction (p < 0.001). Non‐adherence is significantly associated with patients’ beliefs about ISMs, perceived barriers, and lower life satisfaction. Strategies to increase ISM adherence are discussed.
Abnormal circadian blood pressure regulation in liver transplanted children
Authors: Bayrakci Umut Selda , Baskin Esra , Ozcay Figen , Gulleroglu Kaan , Ozbay Ferda , Sevmis Sinasi , Karakayali Hamdi , Haberal Mehmet
Published: February 2012

Bayrakci US, Baskin E, Ozcay F, Gulleroglu K, Ozbay F, Sevmis S, Karakayali H, Haberal M. Abnormal circadian blood pressure regulation in liver transplanted children.  Pediatr Transplantation 2012: 16: 160–164. © 2012 John Wiley & Sons A/S.

Abstract:  HT is a frequent cardiovascular risk factor in liver transplant recipients. However, there are only few studies in the literature regarding the risk of HT in liver transplanted children. The aim of this study was to assess the 24 h BP profiles of liver transplanted patients and to compare the results with healthy children. ABPM was performed on 20 liver transplanted patients and 27 healthy children aged 7.1 ± 4.8 and 8.5 ± 2.9 yr, respectively. HT was defined as SDS > 1.64 (i.e., >95th percentile) adjusted for gender and height. The mean duration of post‐transplant follow‐up was 32 ± 19 months. Six (30%) patients were found to be hypertensive. The physiological nocturnal BP fall was attenuated significantly in the study group for diastolic BP (11.5 ± 6.1 mmHg vs. 17.7 ± 7.1 mmHg, p = 0.006). Specifically, the number of patients with high nighttime systolic and diastolic BP SDS (p = 0.02 and p = 0.004, respectively) as well as elevated nighttime systolic (p = 0.03) and diastolic (p = 0.003) BPLs was found to be significantly higher than those in the controls. Alteration of the “normal” circadian rhythm is very frequent in liver transplant recipients. Thus, it is recommended to perform ABPM on all liver transplanted children not to underdiagnose HT.
Optimised radiological diagnosis of hepatic fungal infection during the treatment of leukemia
Authors: Petrausch Ulf , Frauenfelder Thomas , Mueller Nicolas J. , Arn Kornelius , Stussi Georg , Schanz Urs
Published: February 2012

Hepatic fungal infection is a frequent complication in patients receiving intensive chemotherapy for acute leukaemia. Hepatic lesions may be detected using computerised tomographic (CT) scans, but there is no standardised CT protocol for the diagnosis and follow‐up of hepatic fungal infection. We therefore retrospectively analysed the number and the volume of hepatic fungal lesions in 24 CT of 20 consecutive patients treated for acute leukaemia during late‐arterial and porto‐venous phase. The mean number of lesions per patient was 31 (range: 3–105) in the late‐arterial and 26 (3–81) in the porto‐venous CT (P = 0.026). The mean total volume of all lesions was 6.45 ml in the late‐arterial and 4.07 ml in the porto‐venous CT representing a 1.6fold difference between the two CT scans (P = 0.008). The total volume of the lesions negatively correlated to the absolute contrast difference between liver parenchyma and liver vein (Pearson correlation, r = −0.62; P = 0.002). In conclusion, the late‐arterial CT provides a superior distinction of hepatic lesions due to a delayed perfusion of the outer rim of the fungal lesions resulting in an extended visibility. The late‐arterial CT is superior to the porto‐venous CT for initial diagnosis and follow‐up of hepatic fungal infection.
Family systems psychiatry in an acute in‐patient setting: the implementation and sustainability 5 years after its introduction
Authors: Haun Markus W. , Kordy Henrike , Ochs Matthias , Zwack Julika , Schweitzer Jochen
Published: February 2012

From 2003 to 2008 a multicentre research project, systems therapy methods in acute psychiatry (SYMPA), attempted to establish structured in‐patient treatment based on systemic interventions in German non‐university psychiatric hospitals. Utilising multi‐professional family systems training for team members in six in‐patient wards, its main goal was to improve the involvement of familial and non‐familial important others. This follow‐up study explores the sustainability of family systems psychiatry by evaluating the frequency of the utilisation of four core systemic interventions; elements of a systemic organizational culture in psychiatry; and institutional barriers to this new approach. The degree of implementation was high to moderate, depending on the intervention. More intense communication developed among staff of different professions and the status of nursing staff improved. Organizational barriers to implementation included the ambiguous role of junior doctors in teams, continuously understaffed wards and frequent over‐occupancy.
Topical tacrolimus significantly promotes repigmentation in idiopathic guttate hypomelanosis: a double‐blind, randomized, placebo‐controlled study
Authors: Rerknimitr P. , Disphanurat W. , Achariyakul M.
Published: February 2012

Background  Idiopathic guttate hypomelanosis (IGH) is an idiopathic disorder affecting a large number of people. Effective treatments are not yet available.

Objectives  To investigate the efficacy of topical 0.1% tacrolimus ointment compared with placebo in the treatment of IGH.

Materials and methods  Twenty‐six patients were included in the study. Lesions on one side of the body were selected to have a treatment with 0.1% tacrolimus ointment, whereas those on the other side served as a control with placebo ointment that had the same physical appearance. Colorimeter was used to assess skin colour at baseline and at 1, 2, 3, 4 and 6 months of treatment.

Results  Mean luminosity scale after adjusted for baseline from the treated side gradually decreased and reached statistical significance compared with the control group after 6 months of treatment (P = 0.019). Physicians’ improvement grading score showed that 11% of the patients demonstrated improvement of their skin lesions on the treated side after 6 months’ treatment.

Conclusion  Topical 0.1% tacrolimus ointment appeared to be an effective and safe treatment for IGH. The improvements were best observed by colorimetry, yet, they were not statistically significant upon clinical assessments.
Reflectance confocal microscopy in the diagnosis of partially and completely amelanotic melanoma: report on seven cases
Authors: Maier T. , Sattler E.C. , Braun‐Falco M. , Korting H.C. , Ruzicka T. , Berking C.
Published: February 2012

Background  The clinical diagnosis of amelanotic melanoma is often challenging, because the classical clinical and dermoscopic features of pigmented melanoma are usually missing. The reflectance confocal microscopy (RCM) offers an additional possibility of an in vivo diagnosis of both pigmented and amelanotic melanoma lesions.

Objectives  To test the value of RCM in vivo in the preoperative prediction of melanoma lesions lacking significant pigment and to compare the results with the evaluation by dermoscopy and histopathology.

Methods  We examined seven patients with the clinically uncertain differential diagnosis of partially or completely amelanotic melanoma by RCM and dermoscopy prior to surgical excision of the lesions according to the previously suggested dermoscopy algorithm and RCM score for melanoma. The following RCM features were evaluated: major criteria scored +2 (non‐edged papillae, cytological atypia at the dermo‐epidermal junction) and minor criteria +1 (roundish pagetoid cells, widespread pagetoid infiltration, nucleated cells within dermal papillae, cerebriform cell clusters). The dermoscopic evaluation included the following criteria: polymorphous vessels, dotted and linear irregular vessels, hairpin vessels, pink‐erythematous colour, milky red areas, irregularly shaped depigmentation, blue‐grey dots and subtle pigmentation.

Results  The preoperative in vivo RCM analysis revealed common features of melanoma also found in pigmented melanoma lesions. All lesions showed a score above three in the applied RCM algorithm which was proposed earlier as the threshold for malignancy. In dermoscopy, five of seven lesions showed characteristic vascular changes.

Conclusion  In vivo RCM is a valuable tool in the preoperative diagnosis of partially and completely amelanotic tumours suspicious for melanoma in addition to dermoscopic evaluation.
Aetiology for the covariation between combined type ADHD and reading difficulties in a family study: the role of IQ
Authors: Cheung Celeste H.M. , Wood Alexis C. , Paloyelis Yannis , Arias‐Vasquez Alejandro , Buitelaar Jan K. , Franke Barbara , Miranda Ana , Mulas Fernando , Rommelse Nanda , Sergeant Joseph A. , Sonuga‐Barke Edmund J. , Faraone Stephen V. , Asherson Philip , Kuntsi Jonna
Published: February 2012

Background:  Twin studies using both clinical and population‐based samples suggest that the frequent co‐occurrence of attention deficit hyperactivity disorder (ADHD) and reading ability/disability (RD) is largely driven by shared genetic influences. While both disorders are associated with lower IQ, recent twin data suggest that the shared genetic variability between reading difficulties and ADHD inattention symptoms is largely independent from genetic influences contributing to general cognitive ability. The current study aimed to extend the previous findings that were based on rating scale measures in a population sample by examining the generalisability of the findings to a clinical population, and by measuring reading difficulties both with a rating scale and with an objective task. This study investigated the familial relationships between ADHD, reading difficulties and IQ in a sample of individuals diagnosed with ADHD combined type, their siblings and control sibling pairs.

Methods:  Multivariate familial models were run on data from 1,789 individuals at ages 6–19. Reading difficulties were measured with both rating scale and an objective task. IQ was obtained using the Wechsler Intelligence Scales (WISC–III/WAIS–III).

Results:  Significant phenotypic (.2–.4) and familial (.3–.5) correlations were observed among ADHD, reading difficulties and IQ. Yet, 53%–72% of the overlapping familial influences between ADHD and reading difficulties were not shared with IQ.

Conclusions:  Our finding that familial influences shared with general cognitive ability, although present, do not account for the majority of the overlapping familial influences on ADHD and reading difficulties extends previous findings from a population‐based study to a clinically ascertained sample with combined type ADHD.
Variables affecting teachers' attitudes towards inclusive education in Bangladesh
Authors: Ahmmed Masud , Sharma Umesh , Deppeler Joanne
Published: February 2012

Inclusive education is a worldwide reform strategy intended to include students with different abilities in mainstream regular schools. Evidence from previous research shows that success in implementing effective inclusive teaching practices in the school is contingent on teachers' positive attitudes towards inclusive education. This study was conducted in the context of primary education in Bangladesh aiming to examine variables influencing teachers' attitudes towards inclusion of students with disabilities in regular classrooms. Data for the study was collected from 738 teachers working in 293 government primary schools in Bangladesh. The results indicated thatperceived school support for inclusive teaching practicesand a range of demographic variables includingprevious success in teaching students with disabilitiesandcontact with a student with a disability wereassociated with more positive attitudes of the teachers towards the inclusive education. The results are discussed with possible implications for educators, policy‐makers and international organisations working on the implementation of inclusive education.
Endothelin and bradykinin: ‘brothers‐in‐arms’ in Chagas vasculopathies?
Authors: D'Orléans‐Juste Pedro , Bkaily Ghassan , Rae Giles Alexander
Published: February 2012

Reports of Chagas disease are increasing in non‐endemic populations across the globe. Apart from vector eradication and prevention efforts by public health organizations, current pharmacological interventions are sparse and show important side effects. In this issue of the BJP, Andrade et al. elegantly demonstrate a new pharmacological paradigm whereby Trypanosoma cruzi host cell invasion requires significant cross‐talk between receptors for kinins and endothelins. It is shown, for example, that acting via both ETA and ETB receptors, endothelin‐1 (ET‐1) cooperates with the (TLR2/CXCR2/B2 kinin receptor) complex to activate inflammatory processes in response to invading trypomastigotes.

This study by Andrade et al. prompts, however, several important questions, summarized in this Commentary, such as the putative role of chymase‐dependent production of ET‐1, the contentious protective role of ACE inhibitors in Chagasic patients, the unexplored role of de novo formed B1 receptors for kinins triggered by cytokines and the putative role of compartmentalized calcium pools in host cell invasion by trypomastigotes.

LINKED ARTICLE This article is a commentary on Andrade et al., pp. 1333–1347 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476‐5381.2011.01609.x
Characterization of the hypothermic effects of imidazoline I2 receptor agonists in rats
Authors: Thorn David A , An Xiao‐Fei , Zhang Yanan , Pigini Maria , Li Jun‐Xu
Published: February 2012

BACKGROUND AND PURPOSE Imidazoline I2 receptors have been implicated in several CNS disorders. Although several I2 receptor agonists have been described, no simple and sensitive in vivo bioassay is available for studying I2 receptor ligands. This study examined I2 receptor agonist‐induced hypothermia as a functional in vivo assay of I2 receptor agonism.

EXPERIMENTAL APPROACH Different groups of rats were used to examine the effects of I2 receptor agonists on the rectal temperature and locomotion. The pharmacological mechanisms were investigated by combining I2 receptor ligands and different antagonists.

KEY RESULTS All the selective I2 receptor agonists examined (2‐BFI, diphenyzoline, phenyzoline, CR4056, tracizoline, BU224 and S22687, 3.2–56 mg·kg–1, i.p.) dose‐dependently and markedly decreased the rectal temperature (hypothermia) in rats, with varied duration of action. Pharmacological mechanism of the observed hypothermia was studied by combining the I2 receptor agonists (2‐BFI, BU224, tracizoline and diphenyzoline) with imidazoline I2 receptor/ α2 adrenoceptor antagonist idazoxan, selective I1 receptor antagonist efaroxan, α2 adrenoceptor antagonist/5‐HT1A receptor agonist yohimbine. Idazoxan but not yohimbine or efaroxan attenuated the hypothermic effects of 2‐BFI, BU224, tracizoline and diphenyzoline, supporting the I2 receptor mechanism. In contrast, both idazoxan and yohimbine attenuated hypothermia induced by the α2 adrenoceptor agonist clonidine. Among all the I2 receptor agonists studied, only S22687 markedly increased the locomotor activity in rats.

CONCLUSIONS AND IMPLICATIONS Imidazoline I2 receptor agonists can produce hypothermic effects, which are primarily mediated by I2 receptors. These data suggest that I2 receptor agonist‐induced hypothermia is a simple and sensitive in vivo assay for studying I2 receptor ligands.
Using lean techniques to define the platelet (PLT) transfusion process and cost‐effectiveness to evaluate PLT dose transfusion strategies
Authors: Riley William , Smalley Benjamin , Pulkrabek Shelley , Clay Mary E. , McCullough Jeffrey
Published: February 2012

BACKGROUND: Platelet (PLT) doses of 1.1 × 1011, 2.2 × 1011, and 4.4 × 1011/m2 body surface area are equally effective in preventing bleeding. These different dose strategies involve different numbers of transfusions. We conducted a cost analysis of three separate PLT dose therapies.

STUDY DESIGN AND METHODS: A process map of preparation and administration of a PLT transfusion identified 46 steps (23 steps in the blood bank and 23 steps on the care unit). Time studies were conducted for these 46 steps. Supply costs and personnel costs were estimated based on time studies. We conducted a cost analysis of three separate treatment regimes involving 16 transfusions per patient for the low‐dose, 12 transfusions for medium‐dose, and eight transfusions for high‐dose regimes.

RESULTS: The time and the cost of the transfusion process for the blood bank were 32.41 minutes and $21.93 per unit, and for the patient care unit, 58.36 minutes and $57.71 per unit. The total cost for a course of PLT therapy per patient ranged from $4503.77 to $7014.59 for three different PLT doses. For a simulated bone marrow transplantation unit with 259 patients annually, there would be approximately a $700,000 difference among the clinically equivalent low‐, medium‐, and high‐dose treatment options.

CONCLUSIONS: The overall cost of transfusion therapy is more influenced by the cost of the product than the cost of providing the transfusion. Depending on the cost adjustment by the supplier for different doses of PLTs, a low‐dose transfusion strategy can be less costly.
Cardiovascular disease risk assessment and prevention in blood donors
Authors: Kessler Debra A. , Ortiz Caroline , Grima Kathleen , Vlahov David , Nandi Vijay , Jones Robert , Hillyer Christopher D. , Shaz Beth H.
Published: February 2012

BACKGROUND: Blood centers have implemented public health initiatives, including cardiovascular disease (CVD) screening, to improve donor and community health and serve as an incentive to donate.

STUDY DESIGN AND METHODS: CVD risk screening and counseling were performed at mobile blood drives in diverse neighborhoods. Risk factors were determined by point‐of‐care testing (total cholesterol, high‐density lipoprotein, and hemoglobin A1c levels), interviews, and physical examinations (body mass index, waist circumference, and blood pressure). Results were confidentially relayed to participant by health counselors. A 60‐day follow‐up survey was sent to some participants.

RESULTS: Over 11 months, 2406 participants (44% male; mean age 28 ± 16; 67% minority racial/ethnic group) were screened at 290 mobile drives. A total of 92% of participants had medical insurance. A total of 14% had none, 26% one, 33% two, and 27% three or more risk factors. A total of 72% of teenage participants had at least one risk factor. A total of 18% of participants who were taking medications for risks were poorly controlled. A total of 15% had newly identified risks. A total of 711 participants completed follow‐up survey: 21% sought medical care, 51% were motivated to change their lifestyle, 81% were pleased with screening, 48% were more likely to donate, and 62% recommended donation to friends and family because of the screening.

CONCLUSION: CVD risk screening and counseling can occur during a mobile blood drive. A majority of participants screened had risk factors. Follow‐up surveys showed that the program was well received. Further studies are planned to evaluate long‐term effects of the program on donor health and donor return rates.
Factors associated with the avoidance of red blood cell transfusion after hematopoietic stem cell transplantation
Authors: Kekre Natasha , Christou Grace , Mallick Ranjeeta , Tokessy Melanie , Tinmouth Alan , Tay Jason , Allan David S.
Published: February 2012

BACKGROUND: Red blood cell (RBC) transfusion is required frequently for most patients after hematopoietic stem cell transplantation (HSCT). RBC transfusion, however, can be associated with adverse events including transfusion reactions, acquiring transmissible disease, and delayed recovery. Factors associated with avoidance of transfusion are not well documented.

STUDY DESIGN AND METHODS: Data concerning RBC transfusions between Day 0 and Day +30 were analyzed for patients undergoing HSCT at a single Canadian transplant center between January 2002 and December 2007.

RESULTS: Of 555 patients undergoing HSCT with complete RBC transfusion data, 59 patients (10.6%) did not require RBC transfusion in the first 30 days after HSCT. Univariate analysis showed no significant difference in age, graft source, donor type, or conditioning regimen between transfused and nontransfused patients. Factors that were significantly associated with avoidance of transfusion included male sex (p = 0.0013), diagnosis, specifically plasma cell dyscrasias (p < 0.0001), early‐stage disease (p = 0.006), and higher baseline hemoglobin (Hb) at time of transplant (p < 0.0001). In multivariate analysis, higher pretransplant Hb, male sex, and early‐stage disease remained significantly associated with avoidance of RBC transfusion. Pretransplant Hb correlated inversely with the number of RBC transfusions (r = −0.89).

CONCLUSION: Increased pretransplant Hb, male sex, and early‐stage disease are associated with avoidance of RBC transfusion after HSCT. Interventions aimed at improving pretransplant Hb levels require further study.
Trypanosoma cruzi infection in North America and Spain: evidence in support of transfusion transmission (CME)
Authors: Benjamin Richard J. , Stramer Susan L. , Leiby David A. , Dodd Roger Y. , Fearon Margaret , Castro Emma
Published: February 2012

BACKGROUND: The United States, Canada, and Spain perform selective testing of blood donors for Trypanosoma cruzi infection (Chagas disease) to prevent transfusion transmission. The donor, product, and patient characteristics associated with transfusion‐transmitted infections are reviewed and the infectivity of components from donors with serologic evidence of infection is estimated.

STUDY DESIGN AND METHODS: A systematic review of transfusion‐transmitted T. cruzi cases and recipient tracing undertaken in North America and Spain is described. Cases were assessed for the imputability of the evidence for transfusion transmission.

RESULTS: T. cruzi infection in 20 transfusion recipients was linked to 18 serologically confirmed donors between 1987 and 2011, including 11 identified only by recipient tracing. Cases were geographically widely distributed and were not associated with incident or autochthonous infections. Index clinical cases were described only in immunocompromised patients. All definite transmissions (n = 11) implicated apheresis or whole blood–derived platelets (PLTs), including leukoreduced and irradiated products. There is no evidence of transmission by red blood cells (RBCs) or frozen products, while transmission by whole blood transfusion remains a possibility. Recipient tracing reveals low component infectivity from serologically confirmed, infected donors of 1.7% (95% confidence interval [CI], 0.7%‐3.5%) overall: 13.3% (95% CI, 5.6%‐25.7%) for PLTs, 0.0% (95% CI, 0.0%‐1.5%) for RBCs, and 0.0% (95% CI, 0%‐3.7%) for plasma and cryoprecipitate.

CONCLUSIONS: T. cruzi is transmitted by PLT components from some donors with serologic evidence of infection. Evidence of transmission before the implementation of widespread testing in the countries studied is sparse, and selective testing of only PLT and fresh whole blood donations should be considered.