bluuebunny/crossref_metadata_2025 huggingface dataset:
Antioxidant-rich dietary intervention for improving asthma control in pregnancies complicated by asthma: study protocol for a randomized controlled trial
Authors: Grieger Jessica A , Wood Lisa G , Clifton Vicki L
Published: April 2014

Background

Asthma is the most prevalent chronic disease to complicate pregnancies worldwide, affecting around 12% of pregnant women in Australia. Oxidative stress and inflammation manifest during pregnancy; however asthma in pregnancies further intensifies oxidative stress. Consumption of antioxidant-rich foods has been shown to be beneficial for asthma control in non-pregnant asthmatic adults. It has not been investigated whether antioxidant-rich foods can improve the elevated oxidative stress that occurs with asthma in pregnancy, thereby improving asthma control. The primary aim of this study is to determine whether increased consumption of antioxidant-rich foods for 12 weeks will improve maternal asthma control, compared to standard dietary intake during pregnancy.

Methods/design

A 12 week, parallel randomized controlled trial will be conducted. One hundred and sixty eight pregnant women with mild, moderate, or severe asthma, currently using inhaled corticosteroids, and with poor diet quality, will be recruited at approximately12 weeks gestation. Following a 4 week run-in period, women will be randomized to either a 12 week antioxidant intervention (increased consumption of antioxidant-rich foods (≥5 servings/day vegetables, ≥2 servings/day fruit, ≥8 ½ servings/day grains (mostly wholegrains), 3–4 serving/week lean meat) or standard pregnancy care. The primary outcome is asthma control score (decrease of 0.5, the minimally clinically significant change). Secondary outcomes include plasma antioxidants, markers of oxidative stress, and time to, and number of, exacerbations. With two-tailed t-tests at 80% power, a sample size of 52 completions per group is required. Allowing for a 78% retention including a 20% removal of women from the analysis due to non-compliance, we will recruit 168 women.

Discussion

It is expected that this 12 week study will improve asthma control. This is significant because asthma is the most prevalent condition to complicate pregnancies and contributes to poor maternal, neonatal and infant health outcomes. Our research will provide the first evidence to show that, in pregnancy, consumption of antioxidant-rich foods is a key modifier of clinical asthma status. This research is crucial for contributing to the evidence base to inform future guidelines given existing clinical and research gaps.

Trial registration

ACTRN12613000301763
Prevalence of Fasciola giganticainfection in slaughtered animals in south-eastern Lake Chad area in relation to husbandry practices and seasonal water levels
Authors: Jean-Richard Vreni , Crump Lisa , Abicho Abbani Alhadj , Naré Ngandolo Bongo , Greter Helena , Hattendorf Jan , Schelling Esther , Zinsstag Jakob
Published: April 2014

Background

Fasciolosis has been described in sub-Saharan Africa in many accounts, but the latest reports from Chad are from the 1970s. Mobile pastoralists perceive liver parasites as a significant problem and think that proximity to Lake Chad can lead to infection. This study aimed to assess the importance of liver fluke infections in mobile pastoralists’ livestock in the south-eastern Lake Chad region.

In 2011, all animals presented at three slaughter slabs near Gredaya in the south-eastern Lake Chad area were examined for infection with Fasciola spp. during routine meat inspections.

Results

This study included 616 goats, 132 sheep and 130 cattle. The prevalence of adult Fasciola gigantica was 68% (CI 60-76%) in cattle, 12% (CI 10-16%) in goats and 23% (CI 16-30%) in sheep. From all infected animals (n = 200), 53% (n = 106) were classified as lightly infected with 1-10 parasites, 18% (n =36) as moderately infected with 11-100 parasites and 29% (n = 58) as heavily infected with more than 100 parasites per animal.

Animals grazing close to the shores of Lake Chad had a much higher risk of infection (prevalence =38%; n = 329) than animals not feeding at the lake (n = 353), with only one goat being positive (prevalence = 0.28%).

The ethnic group of the owner was a strong determinant for the risk of infection. Ethnic group likely served as a proxy for husbandry practices. Geospatial distribution showed that animals originating from areas close to the lake were more likely to be infected with F. gigantica than those from more distant areas.

Conclusions

Livestock belonging to ethnic groups which traditionally stay near surface water, and which were reported to feed near Lake Chad, have a high risk of infection with F. gigantica. Pastoralist perception of fasciolosis as a priority health problem was confirmed.

Regular preventive and post-exposure treatment is recommended for animals grazing near the lake. However, further economic analysis is needed.
Single incision thoracoscopic right upper lobectomy with systematic lymph node dissection
Authors: Jeon Hyun Woo , Kim Young-Du , Moon Young Kyu , Wang Young Pil
Published: April 2014

Video-assisted thoracic surgery (VATS) provides less postoperative pain, preservation of the immune response and shorter recovery period, compared with thoracotomy. However, many patients complain of postoperative pain and paresthesia because VATS requires 3 or 4 incisions including a utility incision of 3–5 cm. To overcome this problem, single incision thoracoscopic surgery has emerged; this technique has been adopted for lung cancer surgery since 2010. Complete mediastinal lymph node dissection is the major role of lung cancer surgery. We describe a case of a right upper lobectomy with complete mediastinal lymph node dissection via single incision thoracosopic surgery.
The effect of prime emulsion components as a function of equilibrium headspace concentration of soursop flavor compounds
Authors: Cheong Kok Whye , Tan Chin Ping , Mirhosseini Hamed , Joanne-Kam Wai Yee , Sheikh Abdul Hamid Nazimah , Osman Azizah , Basri Mahiran
Published: April 2014

Background

Perceptions of food products start when flavor compounds are released from foods, transported and appropriate senses in the oral and nose are triggered. However, the long-term stability of flavor compounds in food product has been a major concern in the food industry due to the complex interactions between key food ingredients (e.g., polysaccharides and proteins). Hence, this study was conducted to formulate emulsion-based beverage using natural food emulsifiers and to understand the interactions between emulsion compositions and flavor compounds.

Results

The influences of modified starch (x

1
), whey protein isolate (x

2
), soursop flavor oil (x

3
) and deionized water (x

4
) on the equilibrium headspace concentration of soursop volatile flavor compounds were evaluated using a four-component with constrained extreme vertices mixture design. The results indicated that the equilibrium headspace concentration of soursop flavor compounds were significantly (p < 0.05) influenced by the matrix and structural compositions of the beverage emulsions. Interface formed using modified starch and whey protein isolate (WPI) proved to be capable of inhibiting the release of volatile flavor compounds from the oil to the aqueous phase. Modified starch could retard the overall flavor release through its hydrophobic interactions with volatile flavor compounds and viscosity enhancement effect. Excessive amount of modified starch was also shown to be detrimental to the stability of emulsion system. However, both modified starch and WPI showed to be a much more effective barrier in inhibiting the flavor release of flavor compounds when used as individual emulsifier than as a mixture.

Conclusions

Overall, the mixture design can be practical in elucidating the complex interactions between key food components and volatile flavor compounds in an emulsion system. These studies will be useful for the manufacturers for the formulation of an optimum beverage emulsion with desirable emulsion properties and desirable flavor release profile.
Building a model for encouraging help-seeking for depression: a qualitative study in a Chinese society
Authors: Hui Alison KY , Wong Paul WC , Fu King-wa
Published: April 2014

Background

Clinical depression has been increasingly prevalent in international health statistics but people are often found to be reluctant to seek help when they encounter depression. However, there is no general theory to explain how personal, social and cultural factors affect an individual’s help-seeking intention, nor to guide the design of preventive programmes for such intention once needed.

Methods

Drawing on the theory of planned behavior, we deployed the illness narrative approach and interviewed 18 participants in Hong Kong.

Results

With the diverse results we gathered from the interviews, a behavioral model was built to conceptualize the interplays of various factors in shaping one’s help-seeking intention and behavior for depression. Participants appeared to have a limited view of treatment options and had diverse views of the symptoms of depression, both of which profoundly affected their motivation to seek help.

Conclusions

The role of family and friends and a holistic approach to mental health education were found to be particularly important for encouraging help-seeking behavior in future campaigns concerning depression.
Favorable effects of low-fat and low-carbohydrate dietary patterns on serum leptin, but not adiponectin, among overweight and obese premenopausal women: a randomized trial
Authors: Llanos Adana AM , Krok Jessica L , Peng Juan , Pennell Michael L , Olivo-Marston Susan , Vitolins Mara Z , DeGraffinreid Cecilia R , Paskett Electra D
Published: April 2014

Purpose

The most effective dietary pattern for breast cancer prevention has been greatly debated in recent years. Studies have examined hypocaloric diets, with particular emphasis on macronutrient composition, yielding inconclusive data. The objective of this study was to examine the effects of calorie-restricted low-fat and low-carbohydrate diets (LFD and LCD, respectively) on circulating adipokines among overweight and obese premenopausal women.

Methods

Seventy-nine overweight and obese premenopausal women were randomized to either LFD or LCD, with increased physical activity, for 52 weeks. Serum adiponectin, leptin and the adiponectin-to-leptin ratio (A/L) were measured at baseline, and at weeks 34 and 52 to assess intervention effects.

Results

While there were no significant changes in serum adiponectin concentrations following the LCD and LFD interventions, leptin concentrations significantly decreased by week 34 of the intervention period (LCD: 35.3%,P = 0.004; LFD: 30.0%,P = 0.01), with no difference by intervention arm. At week 52, these reductions were statistically non-significant, indicating a return to baseline levels by the end of the intervention. While there were non-significant increases in the A/L ratio following the LCD and LFD intervention arms, the overall trend, across groups, was marginally significant (P = 0.05) with increases of 16.2% and 35.1% at weeks 34 and 52, respectively.

Conclusions

These findings suggest that caloric-restricted LCD and LFD dietary patterns favorably modify leptin and possibly the A/L ratio, and lend support to the hypothesis that these interventions may be effective for obesity-related breast cancer prevention through their effects on biomarkers involved in metabolic pathways.

Trial registration

Clinical Trial Registration Number:NCT01559194.
Physical activity and total serum bilirubin levels among insulin sensitive and insulin resistant U.S. adults
Authors: Loprinzi Paul D , Abbott Kalen
Published: April 2014

Background

Total serum bilirubin has been identified as a novel biomarker for metabolic disease, with higher levels providing protection against metabolic disease. To our knowledge, only 3 studies, to date, have examined the association between physical activity and total serum bilirubin, with these studies reporting mixed findings. One potential reason for the mixed findings may be the exclusive use of self-report physical activity methodology. The purpose of this study was to examine the association between accelerometer-assessed physical activity and total serum bilirubin among a national sample of U.S. insulin sensitive and insulin resistant adults.

Methods

Data from the 2003–2006 National Health and Nutrition Examination Survey were used. Physical activity was objectively-measured using an accelerometer over a 7 day period. Bilirubin levels were assessed from a blood sample. Data was analyzed in 2013.

Results

After adjusting for age, gender, race-ethnicity, BMI, comorbid illness, cotinine, and poverty level, moderate-to-vigorous physical activity (MVPA) was associated with bilirubin for insulin resistant individuals (β = 0.08; p = 0.04), but not insulin sensitive individuals (β = 0.02; p = 0.38).

Conclusions

MVPA is associated with total serum bilirubin levels among U.S. adults with insulin resistance. Future experimental and prospective studies are needed, with further attention focused on the mechanisms that may help to explain the association between physical activity and bilirubin.
Association of two common polymorphisms of apolipoprotein A5 gene with metabolic syndrome indicators in a North Iranian population, a cross-sectional study
Authors: Halalkhor Sohrab , Jalali Farzad , Tilaki Karimollah Hajian , Shojaei Shahla
Published: April 2014

Background

Metabolic syndrome is an obesity dependent disorder with a worldwide high prevalence. Regarding the high prevalence of Metabolic syndrome in Iran we analyzed the influence of -1131T>C (rs662799) and c.56C>G (S19W, rs3135506) polymorphisms of the novel apolipoprotein gene, ApoA5, on some Metabolic Syndrome indicators in population from north of Iran.

Methods

199 volunteers from Babol city-Iran were divided in two groups of low (N = 99, TG ≤ 103 mg/dl) and high (N = 100, TG ≥ 150 mg/dl) serum levels of Triglycerides (TG). We amplified the gene fragments containing -1131T>C and c.56C>G polymorphisms by PCR method and revealed the polymorphisms by RFLP analysis.

Results

We found a significant association (p = 0.016, Independent t-test) between high levels of TG and -1131T>C polymorphism but not between this polymorphism and serum HDL-C concentrations. Carriers of the C allele had a 1.97 times higher odds ratio to be in the high-TG group than those of the TT genotype (95%, CI = 1.05-3.68). We observed no association between -1131T>C polymorphism with either Waist-to-Hip Ratio (WHR) or Body-Mass-Index (BMI). In the case of c.56C>G polymorphism, although it showed a significant relationship with WHR (p = 0/040, Independent t-test), but failed to correlate with either levels of TG (p = 0.594) or HDL-C (p = 0.640) in serum.

Conclusion

Our study confirms that ApoA5 gene polymorphisms, -1131T>C and c.56C>G are associated with the two criteria of Metabolic Syndrome, TG and WHR, respectively.
Bosentan reverses the pro-fibrotic phenotype of systemic sclerosis dermal fibroblasts via increasing DNA binding ability of transcription factor Fli1
Authors: Akamata Kaname , Asano Yoshihide , Aozasa Naohiko , Noda Shinji , Taniguchi Takashi , Takahashi Takehiro , Ichimura Yohei , Toyama Tetsuo , Sato Shinichi
Published: April 2014

Introduction

Although the pathogenesis of systemic sclerosis (SSc) still remains unknown, recent studies have demonstrated that endothelins are deeply involved in the developmental process of fibrosis and vasculopathy associated with SSc, and a dual endothelin receptor antagonist, bosentan, has a potential to serve as a disease modifying drug for this disorder. Importantly, endothelin-1 (ET-1) exerts a pro-fibrotic effect on normal dermal fibroblasts and bosentan reverses the pro-fibrotic phenotype of SSc dermal fibroblasts. The purpose of this study was to clarify the details of molecular mechanisms underlying the effects of ET-1 and bosentan on dermal fibroblasts, which have not been well studied.

Methods

The mRNA levels of target genes and the expression and phosphorylation levels of target proteins were determined by reverse transcription real-time PCR and immunoblotting, respectively. Promoter assays were performed using a sequential deletion of human α2 (I) collagen (COL1A2) promoter. DNA affinity precipitation and chromatin immunoprecipitation were employed to evaluate the DNA binding ability of Fli1. Fli1 protein levels in murine skin were evaluated by immunostaining.

Results

In normal fibroblasts, ET-1 activated c-Abl and protein kinase C (PKC)-δ and induced Fli1 phosphorylation at threonine 312, leading to the decreased DNA binding of Fli1, a potent repressor of the COL1A2 gene, and the increase in type I collagen expression. On the other hand, bosentan reduced the expression of c-Abl and PKC-δ, the nuclear localization of PKC-δ, and Fli1 phosphorylation, resulting in the increased DNA binding of Fli1 and the suppression of type I collagen expression in SSc fibroblasts. In bleomycin-treated mice, bosentan prevented dermal fibrosis and increased Fli1 expression in lesional dermal fibroblasts.

Conclusions

ET-1 exerts a potent pro-fibrotic effect on normal fibroblasts by activating “c-Abl - PKC-δ - Fli1” pathway. Bosentan reverses the pro-fibrotic phenotype of SSc fibroblasts and prevents the development of dermal fibrosis in bleomycin-treated mice by blocking this signaling pathway. Although the efficacy of bosentan for dermal and pulmonary fibrosis is limited in SSc, the present observation definitely provides us with a useful clue to further explore the potential of the upcoming new dual endothelin receptor antagonists as disease modifying drugs for SSc.
MicroRNA-155 as a proinflammatory regulator via SHIP-1 down-regulation in acute gouty arthritis
Authors: Jin Hye Mi , Kim Tae-Jong , Choi Jung-Ho , Kim Moon-Ju , Cho Young-Nan , Nam Kwang-Il , Kee Seung-Jung , Moon Jang Bae , Choi Seok-Yong , Park Dong-Jin , Lee Shin-Seok , Park Yong-Wook
Published: April 2014

Introduction

Gout is characterized by episodes of intense joint inflammation in response to intra-articular monosodium urate monohydrate (MSU) crystals. miR-155 is crucial for the proinflammatory activation of human myeloid cells and antigen-driven inflammatory arthritis. The functional role of miR-155 in acute gouty arthritis has not been defined. Therefore, the aim of this study was to examine the role of miR-155 in pathogenesis of acute gouty arthritis.

Methods

Samples from 14 patients with acute gouty arthritis and 10 healthy controls (HCs) were obtained. Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were cultured in vitro with MSU crystals, and gene expression (human miR-155 and SHIP-1) were assessed by real-time PCR. THP-1 cells were stimulated by MSU crystals and/or miR-155 transfection and then subjected to Western blot analysis. Levels of human tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1β in cell culture supernatants were measured by Luminex. Immunohistochemistry was performed on formalin-fixed gout tissues with anti–SHIP-1 antibody. A C57BL/6 J male mouse model of gout was used to analyze the expressions of miR-155, SHIP-1, and inflammatory cytokines.

Results

The samples from gouty arthritis were highly enriched in miR-155, with levels of expression being higher than those found in PBMC from HC. Treatment of the cells with MSU crystals strongly induced miR-155. In addition, overexpression of miR-155 in the cells decreased levels of SHIP-1 and promoted production of MSU-induced proinflammatory cytokines, such as TNF-α and IL-1β. Consistent with in vitro observations, miR-155 expression was elevated in the mouse model of gout. The production of inflammatory cytokines was markedly increased in MSU crystal induced peritonitis mice.

Conclusions

Overexpression of miR-155 in the gouty SFMC leads to suppress SHIP-1 levels and enhance proinflammatory cytokines.
A methodology to ensure and improve accuracy of Ki67 labelling index estimation by automated digital image analysis in breast cancer tissue
Authors: Laurinavicius Arvydas , Plancoulaine Benoit , Laurinaviciene Aida , Herlin Paulette , Meskauskas Raimundas , Baltrusaityte Indra , Besusparis Justinas , Dasevicius Darius , Elie Nicolas , Iqbal Yasir , Bor Catherine , Ellis Ian O
Published: April 2014

Introduction

Immunohistochemical Ki67 labelling index (Ki67 LI) reflects proliferative activity and is a potential prognostic/predictive marker of breast cancer. However, its clinical utility is hindered by the lack of standardized measurement methodologies. Besides tissue heterogeneity aspects, the key element of methodology remains accurate estimation of Ki67-stained/counterstained tumour cell profiles. We aimed to develop a methodology to ensure and improve accuracy of the digital image analysis (DIA) approach.

Methods

Tissue microarrays (one 1-mm spot per patient, n = 164) from invasive ductal breast carcinoma were stained for Ki67 and scanned. Criterion standard (Ki67-Count) was obtained by counting positive and negative tumour cell profiles using a stereology grid overlaid on a spot image. DIA was performed with Aperio Genie/Nuclear algorithms. A bias was estimated by ANOVA, correlation and regression analyses. Calibration steps of the DIA by adjusting the algorithm settings were performed: first, by subjective DIA quality assessment (DIA-1), and second, to compensate the bias established (DIA-2). Visual estimate (Ki67-VE) on the same images was performed by five pathologists independently.

Results

ANOVA revealed significant underestimation bias (P < 0.05) for DIA-0, DIA-1 and two pathologists’ VE, while DIA-2, VE-median and three other VEs were within the same range. Regression analyses revealed best accuracy for the DIA-2 (R-square = 0.90) exceeding that of VE-median, individual VEs and other DIA settings. Bidirectional bias for the DIA-2 with overestimation at low, and underestimation at high ends of the scale was detected. Measurement error correction by inverse regression was applied to improve DIA-2-based prediction of the Ki67-Count, in particular for the clinically relevant interval of Ki67-Count < 40%. Potential clinical impact of the prediction was tested by dichotomising the cases at the cut-off values of 10, 15, and 20%. Misclassification rate of 5-7% was achieved, compared to that of 11-18% for the VE-median-based prediction.

Conclusions

Our experiments provide methodology to achieve accurate Ki67-LI estimation by DIA, based on proper validation, calibration, and measurement error correction procedures, guided by quantified bias from reference values obtained by stereology grid count. This basic validation step is an important prerequisite for high-throughput automated DIA applications to investigate tissue heterogeneity and clinical utility aspects of Ki67 and other immunohistochemistry (IHC) biomarkers.
Hemostasis during the early stages of trauma: comparison with disseminated intravascular coagulation
Authors: Oshiro Akiko , Yanagida Yuichiro , Gando Satoshi , Henzan Naomi , Takahashi Isao , Makise Hiroshi
Published: April 2014

Introduction

We tested two hypotheses that disseminated intravascular coagulation (DIC) and acute coagulopathy of trauma-shock (ACOTS) in the early phase of trauma are similar disease entities and that the DIC score on admission can be used to predict the prognosis of patients with coagulopathy of trauma.

Methods

We conducted a retrospective study of 562 trauma patients, including 338 patients whose data were obtained immediately after admission to the emergency department. We collected serial data for the platelet counts, global markers of coagulation and fibrinolysis, and antithrombin levels. DIC was diagnosed according to the Japanese Association for Acute Medicine (JAAM) DIC scoring system, and ACOTS was defined as a prothrombin-time ratio of >1.2.

Results

The higher levels of fibrin/fibrinogen degradation products (FDP) and D-dimer and greater FDP/D-dimer ratios in the DIC patients suggested DIC with the fibrinolytic phenotype. The DIC patients with the fibrinolytic phenotype exhibited persistently lower platelet counts and fibrinogen levels, increased prothrombin time ratios, higher FDP and D-dimer levels, and lower antithrombin levels compared with the non-DIC patients on arrival to the emergency department and during the early stage of trauma. Almost all ACOTS patients met the criteria for a diagnosis of DIC; therefore, the same changes were observed in the platelet counts, global markers of coagulation and fibrinolysis, and antithrombin levels as noted in the DIC patients. The JAAM DIC score obtained immediately after arrival to the emergency department was an independent predictor of massive transfusion and death due to trauma and correlated with the amount of blood transfused.

Conclusions

Patients who develop DIC with the fibrinolytic phenotype during the early stage of trauma exhibit consumption coagulopathy associated with increased fibrin(ogen)olysis and lower levels of antithrombin. The same is true in patients with ACOTS. The JAAM DIC score can be used to predict the prognosis of patients with coagulopathy of trauma.
A prospective study of the impact of serial troponin measurements on the diagnosis of myocardial infarction and hospital and six-month mortality in patients admitted to ICU with non-cardiac diagnoses
Authors: Ostermann Marlies , Lo Jessica , Toolan Michael , Tuddenham Emma , Sanderson Barnaby , Lei Katie , Smith John , Griffiths Anna , Webb Ian , Coutts James , Chambers John , Collinson Paul , Peacock Janet , Bennett David , Treacher David
Published: April 2014

Introduction

Troponin T (cTnT) elevation is common in patients in the Intensive Care Unit (ICU) and associated with morbidity and mortality. Our aim was to determine the epidemiology of raised cTnT levels and contemporaneous electrocardiogram (ECG) changes suggesting myocardial infarction (MI) in ICU patients admitted for non-cardiac reasons.

Methods

cTnT and ECGs were recorded daily during week 1 and on alternate days during week 2 until discharge from ICU or death. ECGs were interpreted independently for the presence of ischaemic changes. Patients were classified into four groups: (i) definite MI (cTnT ≥15 ng/L and contemporaneous changes of MI on ECG), (ii) possible MI (cTnT ≥15 ng/L and contemporaneous ischaemic changes on ECG), (iii) troponin rise alone (cTnT ≥15 ng/L), or (iv) normal. Medical notes were screened independently by two ICU clinicians for evidence that the clinical teams had considered a cardiac event.

Results

Data from 144 patients were analysed (42% female; mean age 61.9 (SD 16.9)). A total of 121 patients (84%) had at least one cTnT level ≥15 ng/L. A total of 20 patients (14%) had a definite MI, 27% had a possible MI, 43% had a cTNT rise without contemporaneous ECG changes, and 16% had no cTNT rise. ICU, hospital and 180-day mortality was significantly higher in patients with a definite or possible MI.

Only 20% of definite MIs were recognised by the clinical team. There was no significant difference in mortality between recognised and non-recognised events.

At the time of cTNT rise, 100 patients (70%) were septic and 58% were on vasopressors. Patients who were septic when cTNT was elevated had an ICU mortality of 28% compared to 9% in patients without sepsis. ICU mortality of patients who were on vasopressors at the time of cTnT elevation was 37% compared to 1.7% in patients not on vasopressors.

Conclusions

The majority of critically ill patients (84%) had a cTnT rise and 41% met criteria for a possible or definite MI of whom only 20% were recognised clinically. Mortality up to 180 days was higher in patients with a cTnT rise.
Exploring the heterogeneity of effects of corticosteroids on acute respiratory distress syndrome: a systematic review and meta-analysis
Authors: Ruan Sheng-Yuan , Lin Hsien-Ho , Huang Chun-Ta , Kuo Ping-Hung , Wu Huey-Dong , Yu Chong-Jen
Published: April 2014

Introduction

The effectiveness of corticosteroid therapy on the mortality of acute respiratory distress syndrome (ARDS) remains under debate. We aimed to explore the grounds for the inconsistent results in previous studies and update the evidence.

Methods

We searched MEDLINE, Cochrane Central Register of Controlled Trials and Web of Science up to December 2013. Eligible studies included randomized clinical trials (RCTs) and cohort studies that reported mortality and that had corticosteroid nonusers for comparison. The effect of corticosteroids on ARDS mortality was assessed by relative risk (RR) and risk difference (RD) for ICU, hospital, and 60-day mortality using a random-effects model.

Results

Eight RCTs and 10 cohort studies were included for analysis. In RCTs, corticosteroids had a possible but statistically insignificant effect on ICU mortality (RD, −0.28; 95% confidence interval (CI), −0.53 to −0.03 and RR, 0.55; 95% CI, 0.24 to 1.25) but no effect on 60-day mortality (RD, −0.01; 95% CI, −0.12 to 0.10 and RR, 0.97; 95% CI, 0.75 to 1.26). In cohort studies, corticosteroids had no effect on ICU mortality (RR, 1.05; 95% CI, 0.74 to 1.49) but non-significantly increased 60-day mortality (RR, 1.30; 95% CI, 0.96 to 1.78). In the subgroup analysis by ARDS etiology, corticosteroids significantly increased mortality in influenza-related ARDS (three cohort studies, RR, 2.45, 95% CI, 1.40 to 4.27).

Conclusions

The effects of corticosteroids on the mortality of ARDS differed by duration of outcome measures and etiologies. Corticosteroids did not improve longer-term outcomes and may cause harm in certain subgroups. Current data do not support routine use of corticosteroids in ARDS. More clinical trials are needed to specify the favorable and unfavorable subgroups for corticosteroid therapy.
Effectively identifying regulatory hotspots while capturing expression heterogeneity in gene expression studies
Authors: J Joo Jong Wha , Sul Jae Hoon , Han Buhm , Ye Chun , Eskin Eleazar
Published: April 2014

Expression quantitative trait loci (eQTL) mapping is a tool that can systematically identify genetic variation affecting gene expression. eQTL mapping studies have shown that certain genomic locations, referred to as regulatory hotspots, may affect the expression levels of many genes. Recently, studies have shown that various confounding factors may induce spurious regulatory hotspots. Here, we introduce a novel statistical method that effectively eliminates spurious hotspots while retaining genuine hotspots. Applied to simulated and real datasets, we validate that our method achieves greater sensitivity while retaining low false discovery rates compared to previous methods.
Effects of the Peroxisome Proliferator-Activated Receptor (PPAR)-δ Agonist GW501516 on Bone and Muscle in Ovariectomized Rats
Authors: Mosti M. P. , Stunes A. K. , Ericsson M. , Pullisaar H. , Reseland J. E. , Shabestari M. , Eriksen E. F. , Syversen U.
Published: April 2014

Estrogen deficiency promotes bone loss and skeletal muscle dysfunction. Peroxisome proliferator-activated receptors (PPARs) have 3 subtypes (α, δ, and γ). PPARγ agonists induce bone loss, whereas PPARα agonists increase bone mass. Although PPARδ agonists are known to influence skeletal muscle metabolism, the skeletal effects are unsettled. This study investigated the musculoskeletal effects of the PPARδ agonist GW501516 in ovariectomized (OVX) rats. Female Sprague Dawley rats, 12 weeks of age, were allocated to a sham-operated group and 3 OVX groups; high-dose GW501516 (OVX-GW5), low-dose GW501516 (OVX-GW1), and a control group (OVX-CTR), respectively (n = 12 per group). Animals received GW501516 or vehicle (methylcellulose) daily for 4 months by gavage. Bone mineral density (BMD) was assessed by dual x-ray absorptiometry at the femur, spine, and whole body. Bone microarchitecture at the proximal tibia was assessed by microcomputed tomography, and dynamic histomorphometry was performed. Quadriceps muscle morphology and the relative expression of mitochondrial proteins were analyzed. Bone metabolism markers and metabolic markers were measured in plasma. After 4 months, the OVX-GW5 group displayed lower femoral BMD than OVX-CTR. Trabecular separation was higher in the GW-treated groups, compared with OVX-CTR. The OVX-GW5 group also exhibited lower cortical area fraction and a higher structure model index than OVX-CTR. These effects coincided with impaired bone formation in both GW groups. The OVX-GW5 group displayed elevated triglyceride levels and reduced adiponectin levels, whereas no effects on muscle morphology or mitochondrial gene expression appeared. In summary, the PPARδ agonist GW501516 negatively affected bone properties in OVX rats, whereas no effects were detected in skeletal muscle.
Neurokinin B Signaling in the Female Rat: a Novel Link Between Stress and Reproduction
Authors: Grachev P. , Li X.F. , Hu M.H. , Li S.Y. , Millar R.P. , Lightman S.L. , O’Byrne K.T.
Published: April 2014

Acute systemic stress disrupts reproductive function by inhibiting pulsatile gonadotropin secretion. The underlying mechanism involves stress-induced suppression of the GnRH pulse generator, the functional unit of which is considered to be the hypothalamic arcuate nucleus kisspeptin/neurokinin B/dynorphin A neurons. Agonists of the neurokinin B (NKB) receptor (NK3R) have been shown to suppress the GnRH pulse generator, in a dynorphin A (Dyn)-dependent fashion, under hypoestrogenic conditions, and Dyn has been well documented to mediate several stress-related central regulatory functions. We hypothesized that the NKB/Dyn signaling cascade is required for stress-induced suppression of the GnRH pulse generator. To investigate this ovariectomized rats, iv administered with Escherichia coli lipopolysaccharide (LPS) following intracerebroventricular pretreatment with NK3R or κ-opioid receptor (Dyn receptor) antagonists, were subjected to frequent blood sampling for hormone analysis. Antagonism of NK3R, but not κ-opioid receptor, blocked the suppressive effect of LPS challenge on LH pulse frequency. Neither antagonist affected LPS-induced corticosterone secretion. Hypothalamic arcuate nucleus NKB neurons project to the paraventricular nucleus, the major hypothalamic source of the stress-related neuropeptides CRH and arginine vasopressin (AVP), which have been implicated in the stress-induced suppression of the hypothalamic-pituitary-gonadal axis. A separate group of ovariectomized rats was, therefore, used to address the potential involvement of central CRH and/or AVP signaling in the suppression of LH pulsatility induced by intracerebroventricular administration of a selective NK3R agonist, senktide. Neither AVP nor CRH receptor antagonists affected the senktide-induced suppression of the LH pulse; however, antagonism of type 2 CRH receptors attenuated the accompanying elevation of corticosterone levels. These data indicate that the suppression of the GnRH pulse generator by acute systemic stress requires hypothalamic NKB/NK3R signaling and that any involvement of CRH therewith is functionally upstream of NKB.
Associations of Size at Birth and Postnatal Catch-up Growth Status With Clinical and Biomedical Characteristics in Prepubertal Girls With Precocious Adrenarche: Preliminary Results
Authors: Uçar Ahmet , Yackobovitch-Gavan Michal , Erol Oğuz Bülent , Yekeler Ensar , Saka Nurçin , Baş Firdevs , Poyrazoğlu Şükran , Bundak Rüveyde , Darendeliler Feyza
Published: April 2014

Context:

The causes of polycystic ovarian syndrome (PCOS) in girls with precocious adrenarche (PA) remain unclear.

Objective:

Our goal was to compare the clinical, biochemical, and ultrasound characteristics of girls with PA whose size at birth was appropriate for gestational age (AGA) vs those born small for gestational age (SGA). PCOS-associated metabolic and morphological correlates were examined.

Design:

Glucose tolerance, ACTH stimulation, and transabdominal ultrasounds were examined in 56 AGA and 31 SGA girls with PA. Bone age and hormonal profiles were determined. SGA girls were divided into 2 groups by catch-up growth (CUG) status. Subgroups were compared.

Results:

Chronological age, Tanner stage for pubarche, ovarian volume, and uterine volume were similar between the groups. SGA girls had lower body mass index and higher bone age-adjusted post-corticotropin cortisol. We found increased body mass index-adjusted mean serum insulin, reduced insulin sensitivity, and reduced IGF-binding protein-1 in SGA girls. Multicystic ovaries were more common in SGA girls (odds ratio [OR] = 9.69, 95% confidence interval [CI] = 3.34–28.15; P < .001). SGA girls without CUG had a higher incidence of multicystic ovaries than CUG counterparts (OR = 8.4, 95% CI = 1.4–19.3; P = .027). Being born SGA (OR = 43.4, 95% CI = 6.9–84.7; P = .001] and exaggerated 17-hydroxyprogesterone response (OR = 15.8, 95% CI = 1.7–49.8; P = .015) were associated with multicystic ovaries.

Conclusions:

Significant differences in hormone levels, insulin sensitivity, and ovarian maturity were found in prepubertal girls with PA who were SGA. Longitudinal follow-up will help determine whether these factors contribute to a specific PCOS phenotype in SGA girls with PA.
Thyroid Hormones and Mortality Risk in Euthyroid Individuals: The Kangbuk Samsung Health Study
Authors: Zhang Yiyi , Chang Yoosoo , Ryu Seungho , Cho Juhee , Lee Won-Young , Rhee Eun-Jung , Kwon Min-Jung , Pastor-Barriuso Roberto , Rampal Sanjay , Han Won Kon , Shin Hocheol , Guallar Eliseo
Published: April 2014

Context:

Hyperthyroidism and hypothyroidism, both overt and subclinical, are associated with all-cause and cardiovascular mortality. The association between thyroid hormones and mortality in euthyroid individuals, however, is unclear.

Objective:

To examine the prospective association between thyroid hormones levels within normal ranges and mortality endpoints.

Setting and Design:

A prospective cohort study of 212 456 middle-aged South Korean men and women who had normal thyroid hormone levels and no history of thyroid disease at baseline from January 1, 2002 to December 31, 2009. Free T4 (FT4), free T3 (FT3), and TSH levels were measured by RIA. Vital status and cause of death ascertainment were based on linkage to the National Death Index death certificate records.

Results:

After a median follow-up of 4.3 years, 730 participants died (335 deaths from cancer and 112 cardiovascular-related deaths). FT4 was inversely associated with all-cause mortality (HR = 0.77, 95% confidence interval 0.63–0.95, comparing the highest vs lowest quartile of FT4; P for linear trend = .01), and FT3 was inversely associated cancer mortality (HR = 0.62, 95% confidence interval 0.45–0.85; P for linear trend = .001). TSH was not associated with mortality endpoints.

Conclusions:

In a large cohort of euthyroid men and women, FT4 and FT3 levels within the normal range were inversely associated with the risk of all-cause mortality and cancer mortality, particularly liver cancer mortality.
Change in Overhauser Effect-enhanced MRI Signal in Response to uPA Highly Expressing in Tumor
Authors: Niidome Takuro , Chijiiwa Nobukatsu , Yamasaki Toshihide , Yamada Ken-ichi , Mori Takeshi , Naganuma Tatsuya , Utsumi Hideo , Ichikawa Kazuhiro , Katayama Yoshiki
Published: April 2014

Dendritic poly(l-lysine) polymers were modified with stable nitroxyl radicals through the substrate peptides of a protease specifically expressed in tumors. Cleavage of the peptides by the protease affected the Overhauser-enhanced MRI (OMRI) signal from the radicals. This system could be the basis of a functional tumor-imaging technique by OMRI.
The Bright Side of Loss Aversion in Dynamic and Competitive Markets
Authors: Kuksov Dmitri , Wang Kangkang
Published: April 2014

A well-established phenomenon of consumer buying behavior is that consumers evaluate prices relative to a reference point and exhibit loss aversion; i.e., their propensity to buy is more negatively affected by prices above the reference point than it is positively affected by prices below the reference point. The objective of this paper is to analytically examine how the competitive strategy and profitability of firms are affected by the presence of consumer loss aversion in the price dimension. Although we assume that consumer loss aversion increases consumer propensity to search for lower prices, we find that it does not necessarily lead to lower prices or profits when firms compete over multiple periods and when the consumer reference price in subsequent periods is affected by current prices. Specifically, consumer loss aversion could lead to higher prices and profits when consumer valuation is sufficiently high relative to search costs and the proportion of consumers with positive search costs is in an intermediate range. We also show that when forward-looking firms incorporate the negative effect of price promotions on future profits, the equilibrium range of price promotions may actually increase.
Hormonal, metabolic and genetic predictors of metformin efficacy in patients with diabetes mellitus and cancer
Authors: Bershteyn Lev Mikhaylovich , Vasil'ev Dmitriy Alexeevich , Ievleva Aglaya Gennadievna , Poroshina Tatiana Evgen'evna , Imyanitov Evgeny Naumovich
Published: April 2014

Aims. To compare hormonal and metabolic profile of type 2 diabetes mellitus patients (T2DM) with or without neoplastic processes with the data from screening for SNPs affecting sensitivity to metformin.To compare the abovementioned parameters including relevant genotype frequency in patients with positive and negative response to metformin.Materials and Methods. A total of 167 patients, all female, aged 43 to 88 years in menopause no shorter than 1 year, with or without history of T2DM were enrolled in this study. 156 patients underwent genetic screening for SNPs that were previously suggested as relevant to metformin efficacy. 55 patients received metformin 1000-1700 g daily with hormonal and metabolic monitoring and assessment of surrogate antineoplastic markers (such as endometrial thickness and mammographic density of mammary glands). Results. There was no unifying hormonal or metabolic phenotype for patients with given metformin-associated SNPs. However, we observed a certain trend for alterations in HOMA-IR and plasma estradiol levels. Dyslipidemia and elevated estradiol levels were positively associated with both types of positive response to metformin ? ?metabolic? and ?antineoplastic? ? though the latter was observed less frequently. Our data suggests that among 8 studied SNPs, the OCT1_R61C genotype (organic cation transporter-1) carriers require more close attention. Conclusion. Larger studies are required for further elucidation of the genetic background for metformin action in patients with various forms of cancer.
Markers for hepatic autoimmune disorders in patients with type 1 diabetes mellitus
Authors: Derevyanko Olga Sergeevna , Dalantaeva Nadejda Sergeevna , Ivanova Olga Nikolaevna , Goncharov Nikolay Petrovich , Nikonova Tatiana Vasil'evna , Smirnova Olga Mikhailovna
Published: April 2014

Aim. To assess the occurrence of autoantibodies characteristic of autoimmune hepatitis in patients with type 1 diabetes mellitus (T1DM), and to analyze clinical features of positive subjects. Materials and Methods. . 84 patients (39 male, 45 female) with T1DM were subdivided into two groups and underwent biochemical, immunologic and instrumental examination. Results. Markers for hepatic autoimmune disorders were found to be highly prevalent in patients with T1DM, even in those asymptomatic according to clinical and instrumental diagnostic methods. Conclusion.  Our data suggests that T1DM patients are at higher risk of corresponding, though possibly asymptomatic autoimmune disorders.
Current report from Russian Diabetic Retinopathy Register
Authors: Lipatov Dmitriy Valentinovich , Aleksandrova Vera Kirillovna , Atarshchikov Dmitriy Sergeevich , Bessmertnaya Elena Grigor'evna , Kon Irina L'vovna , Kuz'min Anatoliy Gennad'evich , Smirnova Nataliya Borisovna , Tolkacheva Anna Anatol'evna , Chistyakov Timofey Alexandrovich
Published: April 2014

A pandemic expansion of diabetes mellitus (DM) observed nowadays across the globe is increasingly acknowledged as a disaster by all peoples of the world. Statistical analysis indicates an annual increase in prevalence of DM in Russian Federation that had reached 3 779 423 registered patients by 01.01.2013. Besides the humanitarian aspects, DM poses severe economic challenges for this country ? challenges that stem both from high mortality and growing disability rate due to limb loss, decrease in visual acuity and need for hemodialysis, plaguing many DM patients. Aim. To produce an epidemiological evaluation based on the dynamics of prevalence of diabetic retinopathy in the Russian Federation ? nationwide and in individual regions ? across the last 13 years. Materials and Methods. Current survey included patients from various regions of the Russian Federation that were examined during epidemiological missions conducted by the federal Endocrinology Research Centre (2000?2009), as well as National Programmes ?Health? (2007) and ?Diabetes ? Learn In Advance? (2012?2013). Results. In the Russian Federation registered more than 630,000 patients with different stages of diabetic retinopathy. The prevalence of diabetic retinopathy among adults (18 years and older) with type 1 diabetes is 35.25%, while in type 2 diabetes - 16.67%. On average, this means that almost one in five patients (17.63%) with diabetes have certain eye problems. Conclusion. In summary, our data indicate a dramatic growth in the rate of diabetic ocular complications, with a particular increase in proliferative diabetic retinopathy, complicated cataract and neovascular glaucoma. These findings call for an even closer attention to early diagnostics, adequate management and, above everything else, timely prevention of ocular pathologies in patients with DM.
Effects of growth factors and cytokins on soft tissue regeneration in patients with diabetes mellitus
Authors: Zaytseva Ekaterina Leonidovna , Tokmakova Alla Yur'evna
Published: April 2014

Delayed wound healing is characteristic of a glycemic disorder and often results in trophic ulcer formation, ? a process still poorly understood but likely multifaceted. Current review addresses latest reports from cellular and molecular studies of soft tissue regeneration in patients with diabetes mellitus.
Vernetzte Regelungen aus der Sicht der Theorie komplexer Netzwerke / Networked Control Systems and Network Science
Authors: Lunze Jan
Published: April 2014

Der Übersichtsbeitrag gibt einen Einblick in die Theorie komplexer Netzwerke und zeigt an drei Anwendungsszenarien, welche Konsequenzen die Ergebnisse dieser Theorie für zentrale Probleme der Regelungstheorie vernetzter Systeme haben und welche wichtigen Fragestellungen sich daraus ergeben. Die Tatsache, dass real existierende komplexe Netze trotz großer Knotenanzahl i. Allg. über kurze Pfade zwischen beliebigen Knotenpaaren verfügen, muss bei vernetzten Regelungssystemen dadurch nachgebildet werden, dass durch eine gezielte Wahl von Kommunikationsverbindungen eine kleine charakteristische Pfadlänge erzeugt wird. Die Anwendungsszenarien weisen darauf hin, dass dabei die Pfadlänge auch von den Übertragungseigenschaften der Teilsysteme bestimmt wird.
Control of Networked Switched Systems Using Passivity and Dissipativity / Regelung vernetzter geschalteter Systeme unter Nutzung von Passivitäts- und Dissipativitätseigenschaften
Authors: McCourt Michael J. , Antsaklis Panos J.
Published: April 2014

Passivity and dissipativity are important in the study of Cyber Physical Systems (CPS) where systems with time and event-driven dynamics are connected. This paper provides conditions which guarantee stability of interconnected switched systems which may be used to model CPS. Results are presented for maintaining stability when switched systems are connected in feedback. Then methods for maintaining stability of passive switched systems that are connected over a network with delays are presented.