bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct dating of thick‐ and thin‐skin thrusts in the Peruvian Subandean zone through apatite (U–Th)/Heand fission track thermochronometry
Authors: Gautheron Cécile , Espurt Nicolas , Barbarand Jocelyn , Roddaz Martin , Baby Patrice , Brusset Stéphane , Tassan‐Got Laurent , Douville Eric
Published: December 2012

Although the structure of the central Peruvian Subandean zone is well defined, the timing of thrust‐related exhumation and Cenozoic sedimentation remain poorly constrained. In this study, we report new apatite (U–Th)/He(AHe) and fission track (AFT) ages from thrust‐belt and foreland strata along three published balanced cross sections.AHedata from the northern, thick‐skinned domain (i.e. Shira Mountain, Otishi Cordillera and Ucayali Basin) show youngAHeages (ranging from 2.6 ± 0.2 to 13.1 ± 0.8 Ma) compared withAFTages (ranging from 101 ± 5 to 133 ± 11 Ma). In the southern Camisea Basin, where deformation is mainly thin‐skinned,AHeandAFTages have been both reset and show young cooling ages (3.7 ± 0.8 Ma and 8 ± 2 Ma respectively). Using low‐temperature thermochronology data and the latest fission track annealing andHediffusion codes, the thermal history of the study area has been reconstructed using inverse modelling. This history includes two steps of erosion: Early Cretaceous and late Neogene, but only Neogene sedimentation and exhumation varies in the different sectors of the study area. From a methodological point of view, largeAHedata dispersion point to the need for refinement ofAHedamage and annealing models. The influence of grain chemistry on damage annealing, multiple age components and the possibility of fission tracks as traps for He need further consideration. For the central Peruvian Subandes,AHeandAFTages combined with balanced cross sections emphasize the dominant control of Paleozoic inheritance rather than climate on Cenozoic infilling and exhumation histories. Finally, our data provide the first field example of how thick‐skinned thrust‐related deformation and exhumation in the Subandes can be directly dated throughAHethermochronology.
Appetite‐regulating hormones from the upper gut: disrupted control of xenin and ghrelin in night workers
Authors: Schiavo‐Cardozo Daniela , Lima Marcelo M. O. , Pareja José Carlos , Geloneze Bruno
Published: December 2012

Objective

Shift work is associated with circadian rhythm disorder, impaired sleep and behavioural changes, including eating habits, predisposing to obesity and metabolic dysfunctions. It involves a neuro‐hormonal dysregulation of appetite towards positive energy balance, including increased ghrelin and decreased leptin, but little is known about other hormones, such as xenin, derived from the upper gut (like ghrelin), and lower gut hormones. Our objective was to compare night workers with day workers in relation to appetite‐regulating hormones and other metabolic parameters.

Design

Cross‐sectional, observational study.

Participants

Twenty‐four overweight women, divided into night shift workers (n = 12) and day shift workers (n = 12).

Measurements

BMI, waist circumference, fat mass percentage; diet composition; Pittsburgh Sleep Quality Index; lipids; adipokines; meal tolerance test curves of glucose, insulin, ghrelin, PYY3‐36, oxyntomodulin, xenin, GLP‐1; insulin sensitivity (Stumvoll index).

Results

Night workers, as compared with day workers, had greater body fat mass percentage and tendency to greater waist circumference despite similar BMI; greater energy intake; impaired sleep; lower insulin sensitivity; increased triglycerides and tendency to increased C‐reactive protein; similar levels of leptin and other adipokines. Night workers had a blunted post‐meal suppression of ghrelin (AUCi0–60 min 19·4 ± 139·9 vs −141·9 ± 9·0 ng/ml·60 min, P < 0·01); blunted rise of xenin (AUC0–180 min 8690·9 ± 2988·2 vs 28 504·4 ± 20 308·3 pg/ml·180 min, P < 0·01) and similar curves of PYY3‐36, oxyntomodulin and GPL‐1.

Conclusion

Compared with day workers within the same BMI range, night workers presented a disrupted control of ghrelin and xenin, associated with behavioural changes in diet and sleep and increased adiposity and related metabolic alterations.
Pituitary stalk interruption syndrome in 58 Chinese patients: clinical features and genetic analysis
Authors: Yang Yan , Guo Qing‐hua , Wang Bao‐an , Dou Jing‐tao , Lv Zhao‐hui , Ba Jian‐ming , Lu Ju‐ming , Pan Chang‐yu , Mu Yi‐ming
Published: December 2012

Objectives

Pituitary stalk interruption syndrome (PSIS) is rare and its clinical features and pathogenesis are poorly understood. This study characterized the clinical and genetic features of PSIS in Chinese patients.

Design and patients

Clinical data of 58 patients with PSIS and 46 patients with GH deficiency but a normal pituitary stalk (NPS) were retrospectively analysed. HESX1, LHX4, OTX2 and SOX3 polymorphisms were screened in 33 PSIS patients, and GH1 and GHRHR in 4 NPS patients.

Results

Deficiency of GH was 100% in both PSIS and NPS groups. Other deficiency rates for PSIS and NPS groups were as follows: ACTH, 77·6% and 23·9%; TSH, 43·1% and 10·9%; LH/FSH, 94·2% and 47·4%; and combined pituitary hormone, 93·1% and 41·3% respectively. In PSIS and NPS patients, the percentages of anterior pituitary hypoplasia were 98·3% and 54·3%, pituitary stalk abnormality were 100% and 0%, and ectopic neurohypophysis were 91·4% and 0%. A novel heterozygous sequence variant (c.142A>T, p.T48S) was found in HESX1 in one PSIS patient, 3 polymorphisms (c.63T>C, p.G21G; c.450C>T, p.N150N; and c.983A>G, p.N328S) in LHX4 in 7, 1 and 31 PSIS patients, respectively, and a hemizygous polymorphism (c.157G>C, p.V53L) in SOX3 in one PSIS patient. No OTX2 abnormality was detected in PSIS patients, and no GH1 or GHRHR polymorphisms in NPS patients.

Conclusions

Compared with NPS, PSIS patients had more severe anterior pituitary hormone deficiency, lower anterior pituitary hormone secretion and higher probability of abnormal pituitary morphology. HESX1, LHX4 and SOX3 polymorphisms may be associated with PSIS.
Circulating interleukin 6 and soluble forms of its receptors in relation to resting energy expenditure in women with anorexia nervosa
Authors: Karczewska‐Kupczewska Monika , Adamska Agnieszka , Nikołajuk Agnieszka , Otziomek Elżbieta , Górska Maria , Kowalska Irina , Strączkowski Marek
Published: December 2012

Context

Anorexia nervosa (AN) is an eating disorder, resulting in sustained low weight and marked decrease in fat mass. Interleukin 6 (IL‐6) may play a role in appetite, energy expenditure and body weight control. IL‐6 acts through binding with membrane receptor (IL‐6R) and activates glycoprotein 130 (gp130) signalling. Both IL‐6R and gp130 are present in the blood in the soluble forms (sIL‐6R and sgp130 respectively). sIL‐6R sensitizes cells towards IL‐6, whereas sgp130 inhibits gp130 signalling.

Objective

To estimate circulating IL‐6/sIL‐6R/sgp130 system and its relationships with body weight and resting energy expenditure (REE) in AN women.

Patients

We examined 19 women with AN and 27 healthy normal‐weight female controls.

Measurements

Indirect calorimetry and the measurement of serum IL‐6, sIL‐6R and sgp130 concentrations were performed in all the subjects.

Results

REE was decreased in AN women (P < 0·001). Serum IL‐6 was higher in AN women in comparison with control group (P = 0·005). Serum sIL‐6R was lower (P = 0·009) and serum sgp130 was higher (P = 0·004) in AN women in comparison with controls. IL‐6 and sIL‐6R were related to REE in the entire study population (r = −0·54, P < 0·001 and r = 0·48, P = 0·001 respectively) and in AN group (r = −0·54, P = 0·024 and r = 0·60, P = 0·011 respectively).

Conclusions

Increased IL‐6 in AN seems to be compensated by the changes in sIL‐6R and sgp130, which are directed towards inhibition of IL‐6 action. The balance between these factors might play a role in the regulation of energy expenditure in AN.
Circulating apelin level in relation to nutritional status in polycystic ovary syndrome and its association with metabolic and hormonal disturbances
Authors: Olszanecka‐Glinianowicz Magdalena , Madej Paweł , Nylec Marcin , Owczarek Aleksander , Szanecki Wojciech , Skałba Piotr , Chudek Jerzy
Published: December 2012

Objective

The aim of the study was to analyse relationships between plasma apelin‐36 and apelin‐12 levels, nutritional status, insulin resistance and hormonal disturbances, as well as plasma adiponectin, leptin and resistin concentrations inPCOSwomen.

Study design patients and measurements

A cross‐sectional study involving 87PCOS(48 obese) and 67 non‐PCOSwomen (36 obese). Anthropometric parameters and body composition were determined. Serum glucose, androgens,FSH,LH,SHBG, insulin, apelin‐36, apelin‐12, adiponectin, leptin and resistin were measured in the fasting state.

Results

Plasma apelin‐36 and apelin‐12 levels were significantly higher in normal weight women than in the obese women withPCOS(3·1 ± 2·2vs1·2 ± 0·7 μg/l,P < 0·001; 2·9 ± 2·4vs0·5 ± 0·7 μg/l;P < 0·001 respectively). Both plasma apelin‐36 and ‐12 levels correlated positively with adiponectin levels, and inversely with leptin or resistin levels. There was a negative correlation between plasma apelin‐36, apelin‐12 and serumLHlevels. In addition, an inverse correlation between apelin‐12 level andLHtoFSHratio was found. In multiple regression analysis 9% ofLHvariability was explained by apelin‐12 levels (β = −0·14;P < 0·001).

Conclusions

Nutritional status seems to have different effects on apelin release, particularly, its active isoform, in women withPCOScompared with women withoutPCOS. This may be partially caused by changes in leptin and resistin secretion and may enhance pituitary‐ovarian axis disturbances. The association between both isoforms of apelin and insulin resistance seems to be bidirectional.
Immunological pathways to β‐cell damage in Type 1 diabetes
Authors: Peakman M.
Published: December 2012

Following almost 30 years of intensive research, initiated by the observation that Type 1 diabetes development is associated with a characteristic pancreatic immune cell infiltrate, a picture is emerging of which of the diverse effector arms of the immune system are involved in β‐cell destruction. Like any chronic pathology, there is considerable complexity, and our ability to model the disease is hampered by a lack of ready access to the target organ and limited longitudinal analyses. However, it seems that putative pathways can start to be ruled in and out, in part as a result of focused mechanistic studies that make use of new technologies, and in part through analysis of the outcomes of clinical trials of new agents aimed at halting the disease process. The picture that emerges suggests a pathway to prevention that may require combinations of therapeutic agents that target different aspects of the immune system and will need to be used with due attention to their risk‐benefit profiles.
Insulin degludec improves health‐related quality of life (SF‐36®) compared with insulin glargine in people with Type 2 diabetes starting on basal insulin: a meta‐analysis of phase 3a trials
Authors: Freemantle N. , Meneghini L. , Christensen T. , Wolden M. L. , Jendle J. , Ratner R.
Published: December 2012

Aim

To compare the effect of insulin degludec and insulin glargine on health‐related quality of life in patients with Type 2 diabetes starting on insulin therapy.

Methods

Patient‐level data from three open‐label, randomized, treat‐to‐target trials of 26 or 52 weeks' duration were pooled using a weighted analysis in conjunction with a fixed‐effects model. Insulin‐naive patients received either insulin degludec (n = 1290) or insulin glargine (n = 632) once daily, in combination with oral anti‐diabetic drugs. Glycaemic control was assessed via HbA1cand fasting plasma glucose concentrations. Rates of hypoglycaemia, defined as plasma glucose < 3.1 mmol/l (< 56 mg/dl), were recorded. Health‐related quality of life was evaluated using the 36‐item Short Form (SF‐36®) version 2 questionnaire. Statistical analysis was performed using a generalized linear model with treatment, trial, anti‐diabetic therapy at baseline, gender, region and age as explanatory variables.

Results

Insulin degludec was confirmed as non‐inferior to insulin glargine based on HbA1cconcentrations. In each trial comprising the meta‐analysis, fasting plasma glucose and confirmed overall and nocturnal (00.01–05.59 h) hypoglycaemia were all numerically or significantly lower with insulin degludec vs. insulin glargine. At endpoint, the overall physical health component score was significantly higher (better) with insulin degludec vs. insulin glargine [+0.66 (95% CI0.04–1.28)], largely attributable to a difference [+1.10 (95% CI0.22–1.98)] in the bodily pain domain score. In the mental domains, vitality was significantly higher with insulin degludec vs. insulin glargine [+0.81 (95% CI0.01–1.59)].

Conclusions

Compared with insulin glargine, insulin degludec leads to improvements in both mental and physical health status for patients with Type 2 diabetes initiating insulin therapy.
Can computerized clinical decision support systems improve diabetes management? A systematic review and meta‐analysis
Authors: Jeffery R. , Iserman E. , Haynes R. B. ,   the CDSS Systematic Review Team
Published: December 2012

Aims

To systematically review randomized trials that assessed the effects of computerized clinical decision support systems in ambulatory diabetes management compared with a non‐computerized clinical decision support system control.

Methods

We included all diabetes trials from a comprehensive computerized clinical decision support system overview completed in January 2010, and searched EMBASE, MEDLINE, INSPEC/COMPENDEX and Evidence‐Based Medicine Reviews (EBMR) from January 2010 to April 2012. Reference lists of related reviews, included articles and Clinicaltrials.gov were also searched. Randomized controlled trials of patients with diabetes in ambulatory care settings comparing a computerized clinical decision support system intervention with a non‐computerized clinical decision support system control, measuring either a process of care or a patient outcome, were included. Screening of studies, data extraction, risk of bias and quality of evidence assessments were carried out independently by two reviewers, and discrepancies were resolved through consensus or third‐party arbitration. Authors were contacted for any missing data.

Results

Fifteen trials were included (13 from the previous review and two from the current search). Only one study was at low risk of bias, while the others were of moderate to high risk of bias because of methodological limitations. HbA1c (3 months' follow‐up), quality of life and hospitalization (12 months' follow‐up) were pooled and all favoured the computerized clinical decision support systems over the control, although none were statistically significant. Triglycerides and practitioner performance tended to favour computerized clinical decision support systems although results were too heterogeneous to pool.

Conclusions

Computerized clinical decision support systems in diabetes management may marginally improve clinical outcomes, but confidence in the evidence is low because of risk of bias, inconsistency and imprecision.
Rapid innate control of antigen abrogates adaptive immunity
Authors: Pembroke Thomas P. I. , Gallimore Awen M. , Godkin Andrew
Published: December 2012

Natural killer (NK) cells provide an immediate first line of defence against viral infections. Memory responses, maintained by CD4+ T cells, require exposure to viral antigen and provide long‐term protection against future infections. It is known that NK cells can promote the development of the adaptive response through cytokine production and cross‐talk with antigen‐presenting cells. In this paper however, we summarize a series of recent publications, in mouse models and for the first time in man, with the unifying message that rapid viral antigen control by the innate immune system limits antigen exposure to CD4+ cells thereby abrogating the development of a memory response. We discuss the significant implication of these studies on viral treatment strategies and immunization models.
Developmental Trajectories of Emotion Regulation Across Infancy: Do Age and the Social Partner Influence Temporal Patterns
Authors: Ekas Naomi V. , Lickenbrock Diane M. , Braungart‐Rieker Julia M.
Published: December 2012

The ability to effectively regulate emotions is a critical component of early socio‐emotional development. This longitudinal study examined the developmental trajectories of emotion regulation in a sample of 3‐, 5‐, and 7‐month‐olds during an interaction with mothers and fathers. Infants' negative affect and use of behavioral strategies, including distraction, self‐soothing, and high intensity motor behaviors were rated during the still‐face episode of the Still‐Face Paradigm. Longitudinal mixed‐effects models were tested to determine whether strategies were followed by an increase or decrease in negative affect. Results from mother‐infant and father‐infant dyads indicated that focusing attention away from the unresponsive parent and engaging in self‐soothing behaviors were associated with a subsequent decline in negative affect and the strength of these temporal associations were stable across infancy. In contrast, high‐intensity motor behaviors were followed by an increase in negative affect and this effect declined over time. No significant effects were found for the behavioral strategy of looking at the parent. Results underscore the importance of considering infant age and the social partner when studying the effectiveness of emotion regulatory strategies in early infancy.
Memory for One‐Time Experiences in the Second Year of Life: Implications for the Status of Episodic Memory
Authors: Bauer Patricia J. , Leventon Jacqueline S.
Published: December 2012

Memory based on a one‐time experience is an important element of its definition as “episodic.” Infants' memories for one‐time experiences over long delays are largely unexplored. Using elicited imitation, we tested 20‐ and 16‐month‐olds' (Experiment 1) and 13‐month‐olds' (Experiment 2) memories as a function of number of experiences and delay. Over 1 month, 20‐ and 16‐month‐olds remembered individual actions of one‐time events; 20‐month‐olds also remembered temporal order; with verbal reminders, 16‐month‐olds did as well. Over 3 months, recall depended on multiple experiences. Thirteen‐month‐olds' required multiple experiences, even over 1 month. The findings speak to the gradual emergence of an important element of episodic memory, namely the ability to preserve memories of one‐time experiences over long periods of time.
A prospective study of chemotherapy immunologic effects and predictors of humoral influenza vaccine responses in a pediatric oncology cohort
Authors: Kersun Leslie S. , Reilly Anne , Coffin Susan E. , Boyer Jean , Luning Prak Eline T. , McDonald Kenyetta , Hou Xiaoling , Jawad Abbas F. , Sullivan Kathleen E.
Published: December 2012

Please cite this paper as: Kersun et al. (2013) A prospective study of chemotherapy immunologic effects and predictors of humoral influenza vaccine responses in a pediatric oncology cohort. Influenza and Other Respiratory Viruses 7(6), 1158–1167.

Background:  Pediatric oncology patients represent a cohort of individuals uniquely at risk of complications from influenza, yet less likely to respond to the vaccine. It is not yet clear how to best protect this vulnerable population.

Methods:  We performed a prospective analysis of 177 pediatric oncology patients to define the predictors of influenza vaccine responses. Each variable was examined over three time points and a repeated measure analysis was performed.

Results:  Patients with ALL vaccinated during induction phase had superior influenza vaccine responses than those subjects vaccinated during post‐induction or maintenance phases (P = 0·0237). Higher aggregate HAI titer responses were associated with a higher baseline B‐cell count (P = 0·0240), and higher CD4 and CD8 influenza‐specific T‐cell responses, suggesting prior antigen exposure is a significant contributor. The solid tumor cohort had equivalent responses during all time frames of chemotherapy.

Discussion:  The optimal protection from influenza of pediatric patients on chemotherapy should include vaccination, but it is clear that not all patients produce high titers of antibodies after vaccination. This study identified biomarkers that could be used to individualize vaccine approaches. Immunologic predictors might have a role in targeting resources, as B‐cell counts predicted of vaccine responses among the patients with ALL.
Pandemic H1N1 influenza surveillance in Haiti, July–December 2009
Authors: Fitter David L. , Freeman Nicole M. , Buteau Josiane , Magloire Roc , Sessions Wendy M. , Guo Lizheng , Katz Mark A. , Boncy Jacques
Published: December 2012

Please cite this paper as: Fitter et al. (2012) Pandemic H1N1 influenza surveillance in Haiti, July–December 2009. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12060.

From June 2009 through December 2009, Haiti conducted sentinel surveillance for influenza. 499 samples were collected and tested using real‐time RT‐PCR. 197 (39.5%) were positive for influenza, including 95 (48%) pandemic (H1N1) 2009, 57 (29%) seasonal influenza A and 45 (23%) influenza B. The median age of pandemic (H1N1) 2009 cases was 21.7; two‐thirds of pandemic (H1N1) 2009 cases were in patients aged 6 years – 35 years. Pandemic activity peaked in September and co‐circulated with other influenza subtypes. The age distribution and seasonality of pandemic (H1N1) 2009 in Haiti were similar to other countries in the Caribbean region.
Comparison of therapeutic effect of topical Nigella with Betamethasone and Eucerin in hand eczema
Authors: Yousefi M. , Barikbin B. , Kamalinejad M. , Abolhasani E. , Ebadi A. , Younespour S. , Manouchehrian M. , Hejazi S.
Published: December 2012

Background  Nigella sativa has been used in traditional medicine. Although it was investigated in different studies, its effect on hand eczema has not been studied yet.

Objective  To compare the effects of Nigella, Betamethasone and Eucerin on severity of hand eczema and patients’ life quality.

Methods  In this randomized, controlled, double‐blinded clinical trial, we allocated new cases of hand eczema with 18–60 years of age in three therapeutic groups (Nigella, Betamethasone and Eucerin) by using permuted blocks for randomization. Patients applied medications twice a day and followed in a 4‐week period. The primary outcome of the study was changes in severity and life quality, which were assessed at the beginning, 14th and 28th days of the study by Hand Eczema Severity index (HECSI) and Dermatology Life Quality Index (DLQI) respectively.

Results  Sixty patients recruited in the study with 20 patients allocated in each study arm. Eighteen, 19 and 15 patients in Eucerin, Nigella and Betamethasone groups, respectively, attended at least one of the therapy sessions. Nigella and Betamethasone showed significantly more rapid improvement in hand eczema compared with Eucerin (P = 0.003 and P = 0.012 respectively); Nigella and Betamethasone ointments caused significant decreases in DLQI scores compared with Eucerin (P < 0.0001 and P = 0.007 respectively). No significant difference was detected in mean DLQI and HECSI of the Nigella and Betamethasone groups over time (P = 0.38 and P = 0.99 respectively).

Conclusion  It seems that Nigella might have the same efficacy as Betamethasone in improvement of life quality and decreasing severity of hand eczema.
Postoperative DAV‐IFN‐β therapy does not improve survival rates of stage II and stage III melanoma patients significantly
Authors: Matsumoto T. , Yokota K. , Sawada M. , Sakakibara A. , Shibata S. , Yasue S. , Tomita Y. , Yatsuya H. , Akiyama M.
Published: December 2012

Background  DAV‐interferon (IFN)‐β therapy is a combination chemotherapy of dacarbazine (DTIC), nimustine (ACNU) and vincristine (VCR) with local subcutaneous injection of IFN‐β that is widely employed as postoperative adjuvant chemotherapy to treat malignant melanoma in Japan. However, the efficacy of DAV‐IFN‐β therapy has not been confirmed by randomized controlled trials and the benefit of DAV‐IFN‐β therapy has not been established yet. This study evaluated the contribution of DAV‐IFN‐β therapy to improve survival of postoperative patients with cutaneous melanoma.

Methods Patients with stage II or III cutaneous melanoma seen at Nagoya University Hospital from January 1998 to December 2009 were eligible for this study. Disease‐free survival rates and melanoma‐specific survival rates were evaluated. A propensity score was calculated to control for the effects of variables related to decisions regarding the application of DAV‐IFN‐β therapy.

Results  Eighty‐two stage II and 60 stage III melanoma patients were included. In the post‐matched stage II patients (17 matched pairs), the mean (±SE) disease‐free survival rates were 39.9±13.7% for DAV‐IFN‐β therapy and 73.1±11.7% for non‐use (hazard ratio for recurrence, 2.06; 95% CI, 0.63–6.69; P = 0.23), and the melanoma‐specific survival rates were 66.2±20.0% for DAV‐IFN‐β therapy and 86.2±9.1% for non‐use (hazard ratio for death, 1.09; 95% CI, 0.17–6.82; P = 0.93). In the post‐matched stage III patients (nine matched pairs), the disease‐free survival rates were 29.6±16.4% for DAV‐IFN‐β therapy and 33.3±15.7% for non‐use (0.69; 95% CI, 0.22–2.17; P = 0.53), and the melanoma‐specific survival rates were 55.6±16.6% for DAV‐IFN‐β therapy and 44.4±16.6% for non‐use (0.67; 95% CI, 0.18–2.50; P = 0.55).

Conclusions  DAV‐IFN‐β therapy brought no significant improvement in either disease‐free survival rates or melanoma‐specific survival rates of patients with stage II or III cutaneous melanoma. A randomized controlled trial would be required to further evaluate the efficacy of DAV‐IFN‐β therapy as an adjuvant chemotherapy.
Dermoscopy of apocrine hidrocystomas: a morphological study
Authors: Zaballos P. , Bañuls J. , Medina C. , Salsench E. , Serrano P. , Guionnet N.
Published: December 2012

Background  The dermoscopic morphology of apocrine hidrocystomas remains to be elucidated.

Objective  To evaluate the morphological findings of apocrine hidrocystomas under dermoscopic observation.

Methods  Dermoscopic examination of 22 cases of apocrine hidrocystomas was performed to evaluate specific dermoscopic criteria and patterns.

Results  The most frequently occurring dermoscopic features were found to be: (i) A translucent to opaque, homogeneous area which occupies the whole lesion in all apocrine hidrocystomas (100%). The colour of this homogeneous area was skin‐colored in 31.8% of our cases; yellow, in 31.8% and blue, in 22.7% of apocrine hidrocystomas. (ii) Vascular structures were identified in 81.8% of our cases; arborizing vessels, in 68.2% and linear‐irregular vessels in 9.1% of our cases; and (iii) Whitish structures were identified in 22.7% of the lesions. The results of our study reveal that the presence of a homogeneous area that occupies the whole lesion and arborizing vessels is the most common dermoscopic pattern in apocrine hidrocystomas (68.2%).

Conclusion  Apocrine hidrocystomas, above all in its pigmented variant, may represent a dermoscopic pitfall, being difficult to differentiate clinically and dermoscopically from basal cell carcinomas.
Pleuro‐pulmonary endometriosis in baboons (Papio spp.): insights into pathogenesis
Authors: Jagirdar J. , Sirohi D. , Dick E.J. , Hubbard G.
Published: December 2012

Background

Human pleuro‐pulmonary endometriosis (PPE) is rare. Recently, we identified several cases of abdominal endometriosis in baboons that developed PPE.

Materials and Methods

Ten cases of PPE and four of intra‐abdominal endometriosis (three simultaneous) were identified at necropsy in baboons (Papio spp.) found dead due to natural causes. The endometriotic lesions were evaluated using immunohistochemistry.

Results

The stromal (CD10+) and epithelial cells in intra‐abdominal cases were estrogen and progesterone receptor (ER/PR) positive and thyroid transcription factor 1 (TTF‐1) negative similar to that seen in humans. In contrast, the PPE cases displayed TTF‐1‐positive epithelium lining the cystic spaces, while the stroma was ER/PR positive similar to that in abdominal endometriosis. Both lymph nodes and spindle cell rests in lung interstitium contained ER/PR‐positive stromal cells.

Conclusions

The lung lesions were different from the abdominal lesions in having a TTF‐1‐positive lining epithelium. The deep pulmonary interstitial and lymph node endometrial stromal rests probably arrive via lymphatic route. The endometrial stroma is the driving force in PPE upon which the lung‐specific epithelium condenses and may require a novel approach to therapy.
Complement component 3 inhibition by an antioxidant is neuroprotective after cerebral ischemia and reperfusion in mice
Authors: Yang Jiwon , Ahn Hye‐na , Chang Minsun , Narasimhan Purnima , Chan Pak H. , Song Yun Seon
Published: December 2012

Oxidative stress after stroke is associated with the inflammatory system activation in the brain. The complement cascade, especially the degradation products of complement component 3, is a key inflammatory mediator of cerebral ischemia. We have shown that pro‐inflammatory complement component 3 is increased by oxidative stress after ischemic stroke in mice using DNA array. In this study, we investigated whether up‐regulation of complement component 3 is directly related to oxidative stress after transient focal cerebral ischemia in mice and oxygen‐glucose deprivation in brain cells. Persistent up‐regulation of complement component 3 expression was reduced in copper/zinc‐superoxide dismutase transgenic mice, and manganese‐superoxide dismutase knock‐out mice showed highly increased complement component 3 levels after transient focal cerebral ischemia. Antioxidant N‐tert‐butyl‐α‐phenylnitrone treatment suppressed complement component 3 expression after transient focal cerebral ischemia. Accumulation of complement component 3 in neurons and microglia was decreased by N‐tert‐butyl‐α‐phenylnitrone, which reduced infarct volume and impaired neurological deficiency after cerebral ischemia and reperfusion in mice. Small interfering RNA specific for complement component 3 transfection showed a significant increase in brain cells viability after oxygen‐glucose deprivation. Our study suggests that the neuroprotective effect of antioxidants through complement component 3 suppression is a new strategy for potential therapeutic approaches in stroke.
Utility of oral cancer diagnostic adjuncts in the adult US populations
Authors: Bhoopathi Vinodh , Mascarenhas Ana Karina
Published: December 2012

Background

Utility of diagnostic adjuncts (DAs) in an adult population with a low oral and pharyngeal cancer (OPC) prevalence is unclear. In this study, we compare the effectiveness of DAs and clinicians' conventional oral examination (COE) in detecting oral and pharyngeal cancers (OPC), in high‐risk (HR) users, low‐risk (LR) and alcohol, and in the overall adult US populations (GP).

Methods

We assumed oral cancer DAs to have 99% sensitivity and specificity. For COE, 79.6% sensitivity and 97.7% specificity were used. Using Altman's mathematical model, the positive predictive values (PPV) for a DA and COE were estimated for HR, LR, and GP groups, respectively. Three different scenarios (sensitivity constant but decreasing specificity, specificity constant but decreasing sensitivity, and decreasing both sensitivity and specificity simultaneously) were developed to simulate the true effectiveness of DAs while keeping the prevalence of OPC in HR, LR, and GP groups constant at 0.4039%, 0.0362%, and 0.1109%, respectively.

Results

The PPVs for a DA in HR, LR, and GP groups in the United States were estimated at 29%, 3%, and 10%, while for COE, the PPVs would be at 12%, 1%, and 4%, respectively.

Conclusions

Utility of DAs in LR and GP groups is negligible due to very low OPC prevalence in these populations. In HR population, DAs may have a slightly better effectiveness than clinicians only when assumed to have high sensitivity and specificity.
Divergent Effects of Aging and Sex on Vasoconstriction to Endothelin in Coronary Arterioles
Authors: LeBlanc Amanda J. , Chen Bei , Dougherty Patrick J. , Reyes Rafael A. , Shipley Robert D. , Korzick Donna H. , Muller‐Delp Judy M.
Published: December 2012

Objective

The risk for cardiovascular disease increases with advancing age; however, the chronological development of heart disease differs in males and females. The purpose of this study was to determine whether age‐induced alterations in responses of coronary arterioles to the endogenous vasoconstrictor, endothelin, are sex‐specific.

Methods

Coronary arterioles were isolated from young and old male and female rats to assess vasoconstrictor responses to endothelin (ET), and ETa and ETb receptor inhibitors were used to assess receptor‐specific signaling.

Results

In intact arterioles from males, ET‐induced vasoconstriction was reduced with age, whereas age increased vasoconstrictor responses to ET in intact arterioles from female rats. In intact arterioles from both sexes, blockade of either ETa or ETb eliminated age‐related differences in responses to ET; however, denudation of arterioles from both sexes revealed age‐related differences in ETa‐mediated vasoconstriction. In arterioles from male rats, ETa receptor protein decreased, whereas ETb receptor protein increased with age. In coronary arterioles from females, neither ETa nor ETb receptor protein changed with age, suggesting age‐related changes in ET signaling occur downstream of ET receptors.

Conclusions

Thus, aging‐induced alterations in responsiveness of the coronary resistance vasculature to endothelin are sex‐specific, possibly contributing to sexual dimorphism in the risk of cardiovascular disease with advancing age.
Corneal changes following near work in myopic anisometropia
Authors: Vincent Stephen J , Collins Michael J , Read Scott A , Carney Leo G , Yap Maurice KH
Published: December 2012

Purpose

To examine the symmetry of corneal changes following near work in the fellow eyes of non‐amblyopic myopic anisometropes.

Methods

Thirty‐four non‐amblyopic, myopic anisometropes (minimum 1 D spherical equivalent anisometropia) had corneal topography measured before and after a controlled near work task. Subjects were positioned in a headrest to minimise head movements and read continuous text on a computer monitor for 10 min at an angle of 25 degrees downward gaze and an accommodation demand of 2.5 D. Measures of the morphology of the palpebral aperture during primary and downward gaze were also obtained.

Results

The more and less myopic eyes exhibited a high degree of interocular symmetry for measures of palpebral aperture morphology during both primary and downward gaze. Following the near work task, fellow eyes also displayed a symmetrical change in superior corneal topography (hyperopic defocus) which correlated with the position of the upper eyelid during downward gaze. Greater changes in the spherical corneal power vector (M) following reading were associated with a narrower palpebral aperture during downward gaze (p = 0.07 for more myopic and p = 0.03 for less myopic eyes). A significantly greater change in J0 (an increase in against the rule astigmatism) was observed in the more myopic eyes (−0.04 ± 0.04 D) compared to the less myopic eyes (−0.02 ± 0.06 D) over a 6 mm corneal diameter (p = 0.01).

Conclusions

Changes in corneal topography following near work are highly symmetrical between the fellow eyes of myopic anisometropes due to the interocular symmetry of the palpebral aperture. However, the more myopic eye exhibits changes in corneal astigmatism of greater magnitude compared to the less myopic eye.
IL‐1β and IL‐6 activate inflammatory responses of astrocytes against Naegleria fowleri infection via the modulation of MAPKs and AP‐1
Authors: Kim J.‐H. , Song A.‐R. , Sohn H.‐J. , Lee J. , Yoo J.‐K. , Kwon D. , Shin H.‐J.
Published: December 2012

Naegleria fowleri, a free‐living amoeba, has been found in diverse habitats throughout the world. It causes primary amoebic meningoencephalitis in children and young adults. The amoeba attaches to nasal mucosa, migrates along olfactory nerves and enters the brain. Astrocytes are involved in the defence against infection and produce inflammatory responses. In this study, we focus on the mechanism of immune responses in astrocytes. We showed, using RNase protection assay, RT‐PCR and ELISA in an in vitro culture system, that N. fowleri lysates induce interleukin‐1beta (IL‐1β) and IL‐6 expression of astrocytes. In addition, cytokine levels of astrocytes gradually decreased due to extracellular signal‐regulated kinase (ERK), c‐Jun N‐terminal kinase (JNK) and p38 inhibitors. To determine the transcription factor, we used transcription inhibitor (AP‐1 inhibitor), which downregulated IL‐1β and IL‐6 expression. These results show that AP‐1 is related to IL‐1β and IL‐6 production. N. fowleri‐mediated IL‐1β and IL‐6 expression requires ERK, JNK and p38 mitogen‐activated protein kinases (MAPKs) activation in astrocytes. These findings show that N. fowleri‐stimulated astrocytes in an in vitro culture system lead to AP‐1 activation and the subsequent expressions of IL‐1β and IL‐6, which are dependent on ERK, JNK and p38 MAPKs activation. These results may imply that proinflammatory cytokines have important roles in inflammatory responses to N. fowleri infection.
N‐glycan maturation is crucial for cytokinin‐mediated development and cellulose synthesis in Oryza sativa
Authors: Fanata Wahyu Indra Duwi , Lee Kyoung Hwan , Son Bo Hwa , Yoo Jae Yong , Harmoko Rikno , Ko Ki Seong , Ramasamy Nirmal Kumar , Kim Kyung Hwa , Oh Doo‐Byoung , Jung Hyun Suk , Kim Jae‐Yean , Lee Sang Yeol , Lee Kyun Oh
Published: December 2012

To explore the physiological significance of N‐glycan maturation in the plant Golgi apparatus, gnt1, a mutant with loss of N‐acetylglucosaminyltransferase I (GnTI) function, was isolated in Oryza sativa. gnt1 exhibited complete inhibition of N‐glycan maturation and accumulated high‐mannose N‐glycans. Phenotypic analyses revealed that gnt1 shows defective post‐seedling development and incomplete cell wall biosynthesis, leading to symptoms such as failure in tiller formation, brittle leaves, reduced cell wall thickness, and decreased cellulose content. The developmental defects of gnt1 ultimately resulted in early lethality without transition to the reproductive stage. However, callus induced from gnt1 seeds could be maintained for periods, although it exhibited a low proliferation rate, small size, and hypersensitivity to salt stress. Shoot regeneration and dark‐induced leaf senescence assays indicated that the loss of GnTI function results in reduced sensitivity to cytokinin in rice. Reduced expression of A‐type O. sativa response regulators that are rapidly induced by cytokinins in gnt1 confirmed that cytokinin signaling is impaired in the mutant. These results strongly support the proposed involvement of N‐glycan maturation in transport as well as in the function of membrane proteins that are synthesized via the endomembrane system.
Elevated energy coupling and aerobic capacity improves exercise performance in endurance‐trained elderly subjects
Authors: Conley Kevin E. , Jubrias Sharon A. , Cress M. Elaine , Esselman Peter C.
Published: December 2012

New Findings

What is the central question of this study?

Does exercise performance reflect the improvements in mitochondrial capacity and energy coupling efficiency found with endurance training in elderly subjects?

What is the main finding and its importance?

Exercise performance of the elderly benefits from elevations in energy coupling and oxidative phosphorylation capacity at both the whole‐body and muscle levels that accompany endurance training.

Increased maximal oxygen uptake (), mitochondrial capacity and energy coupling efficiency are reported after endurance training (ET) in adult subjects. Here we test whether leg exercise performance (power output of the legs, Pmax, at ) reflects these improvements with ET in the elderly. Fifteen male and female subjects were endurance trained for a 6 month programme, with 13 subjects (69.5 ± 1.2 years old, range 65–80 years old; n= 7 males; n= 6 females) completing the study. This training significantly improved Pmax (Δ17%; P= 0.003), (Δ5.4%; P= 0.021) and the increment in oxygen uptake () above resting (; Δ9%; P < 0.02). In addition, evidence of improved energy coupling came from elevated leg power output per unit at the aerobic capacity [Δ(Pmax/); P= 0.02] and during submaximal exercise in the ramp test as measured by delta efficiency (ΔPex/Δ; P= 0.04). No change was found in blood lactate, muscle glycolysis or fibre type. The rise in Pmax paralleled the improvement in muscle oxidative phosphorylation capacity (ATPmax) in these subjects. In addition, the greater exercise energy coupling [Δ(Pmax/) and delta efficiency] was accompanied by increased mitochondrial energy coupling as measured by elevated ATP production per unit mitochondrial content in these subjects. These results suggest that leg exercise performance benefits from elevations in energy coupling and oxidative phosphorylation capacity at both the whole‐body and muscle levels that accompany endurance training in the elderly.
Patients’ silence towards the healthcare system after ethical transgressions by staff: associations with patient characteristics in a cross-sectional study among Swedish female patients
Authors: Brüggemann A Jelmer , Swahnberg Katarina
Published: December 2012

Objectives

To identify which patient characteristics are associated with silence towards the healthcare system after experiences of abusive or ethically wrongful transgressive behaviour by healthcare staff.

Design

Cross-sectional questionnaire study using the Transgressions of Ethical Principles in Health Care Questionnaire.

Setting

A women's clinic in the south of Sweden.

Participants

Selection criteria were: consecutive female patients coming for an outpatient appointment, ≥18-year-old, with the ability to speak and understand the Swedish language, and a known address.

Questionnaires were answered by 534 women (60%) who had visited the clinic, of which 293 were included in the present study sample.

Primary outcome measure

How many times the respondent remained silent towards the healthcare system relative to the number of times the respondent spoke up.

Results

Associations were found between patients’ silence towards the healthcare system and young age as well as lower self-rated knowledge of patient rights. Both variables showed independent effects on patients’ silence in a multivariate model. No associations were found with social status, country of birth, health or other abuse.

Conclusions

The results offer opportunities for designing interventions to stimulate patients to speak up and open up the clinical climate, for which the responsibility lies in the hands of staff; but more research is needed.
Validity of theInternational Classification of Diseases, Tenth Revisioncode for acute kidney injury in elderly patients at presentation to the emergency department and at hospital admission
Authors: Hwang Y Joseph , Shariff Salimah Z , Gandhi Sonja , Wald Ron , Clark Edward , Fleet Jamie L , Garg Amit X
Published: December 2012

Objective

To evaluate the validity of theInternational Classification of Diseases, Tenth Revision(ICD-10) code N17x for acute kidney injury (AKI) in elderly patients in two settings: at presentation to the emergency department and at hospital admission.

Design

A population-based retrospective validation study.

Setting

Southwestern Ontario, Canada, from 2003 to 2010.

Participants

Elderly patients with serum creatinine measurements at presentation to the emergency department (n=36 049) or hospital admission (n=38 566). The baseline serum creatinine measurement was a median of 102 and 39 days prior to presentation to the emergency department and hospital admission, respectively.

Main outcome measures

Sensitivity, specificity and positive and negative predictive values of ICD-10 diagnostic coding algorithms for AKI using a reference standard based on changes in serum creatinine from the baseline value. Median changes in serum creatinine of patients who were code positive and code negative for AKI.

Results

The sensitivity of the best-performing coding algorithm for AKI (defined as a ≥2-fold increase in serum creatinine concentration) was 37.4% (95% CI 32.1% to 43.1%) at presentation to the emergency department and 61.6% (95% CI 57.5% to 65.5%) at hospital admission. The specificity was greater than 95% in both settings. In patients who were code positive for AKI, the median (IQR) increase in serum creatinine from the baseline was 133 (62 to 288) µmol/l at presentation to the emergency department and 98 (43 to 200) µmol/l at hospital admission. In those who were code negative, the increase in serum creatinine was 2 (−8 to 14) and 6 (−4 to 20) µmol/l, respectively.

Conclusions

The presence or absence of ICD-10 code N17× differentiates two groups of patients with distinct changes in serum creatinine at the time of a hospital encounter. However, the code underestimates the true incidence of AKI due to a limited sensitivity.
Overarching goals: a strategy for improving healthcare quality and safety?
Authors: Nanji Karen C , Ferris Timothy G , Torchiana David F , Meyer Gregg S
Published: December 2012

The management literature reveals that many successful organisations have strategic plans that include a bold ‘stretch-goal’ to stimulate progress over a ten-to-thirty-year period. A stretch goal is clear, compelling and easily understood. It serves as a unifying focal point for organisational efforts. The ambitiousness of such goals has been emphasised with the phrase Big Hairy Audacious Goal (‘BHAG’). President Kennedy's proclamation in 1961 that ‘this Nation should commit itself to achieving the goal, before this decade is out, of landing a man on the moon and returning him safely to earth’ provides a famous example. This goal energised the US National Aeronautics and Space Administration, and it captured the attention of the American public and resulted in one of the largest accomplishments of any organisation. The goal set by Sony, a small, cash-strapped electronics company in the 1950s, to change the poor image of Japanese products around the world represents a classic BHAG. Few examples of quality goals that conform to the BHAG definition exist in the healthcare literature. However, the concept may provide a useful framework for organisations seeking to transform the quality of care they deliver. This review examines the merits and cautions of setting overarching quality goals to catalyse quality improvement efforts, and assists healthcare organisations with determining whether to adopt these goals.