bluuebunny/crossref_metadata_2025 huggingface dataset:
A multicentre, randomized, single‐blind comparison of topical clindamycin 1%/benzoyl peroxide 5% once‐daily gel versus clindamycin 1% twice‐daily gel in the treatment of mild to moderate acne vulgaris in Chinese patients
Authors: Xu J.H. , Lu Q.J. , Huang J.H. , Hao F. , Sun Q.N. , Fang H. , Gu J. , Dong X.Q. , Zheng J. , Luo D. , Li F.Q. , Wang G. , Gu H. , Tian H.Q. , Yang H.L. , Xi L.Y. , Li M. , Zheng M. , Wu Y. , Tu Y.T. , He Y.L. , Zhao G. , Sheng W.X. , Li J. , Hamedani A.G.
Published: April 2016

Background

Acne vulgaris affects up to 54% of Chinese adolescents. Combination therapy has become the recommended standard of care for acne.

Objective

The aim of this study was to compare the efficacy and safety of clindamycin (1%) and benzoyl peroxide (5%) (CDP/BPO) gel once daily vs. clindamycin (1%) (CDP) monotherapy gel twice daily in Chinese patients with mild to moderate acne.

Methods

1020 patients (aged 12–45 years) with mild to moderate acne were randomized (1 : 1); 1016 patients were treated with CDP/BPO (n = 500) or CDP (n = 516) for a 12‐week treatment period. Efficacy assessments were performed at baseline, and at weeks 1, 2, 4, 8 and 12; and primarily included change in total lesion count (inflammatory and non‐inflammatory lesions), and proportion of patients with a minimum 2‐grade improvement in Investigator's Static Global Assessment (ISGA) score. Patient safety and local tolerability were also evaluated.

Results

Patients in CDP/BPO group showed a greater per cent reduction in total lesion count compared with patients in CDP group at week 12 (delta = −0.05; 95% CI = −0.09, −0.02; P = 0.003); statistically significant reduction in lesion count was noted as early as week 1 and continued through week 12. A greater proportion of patients in CDP/BPO group showed a ≥2‐grade improvement in ISGA score at week 12 compared with CDP group (30.2% vs. 22.7%; P = 0.018). Overall, the incidence of adverse events (AEs) was higher in the CDP/BPO group (14.4%) than in the CDP group (7.9%); the most commonly reported events were generally related to application site reactions (erythema, pruritus and swelling). Incidence of drug‐related AEs was 8.6% in CDP/BPO group and 1.2% in CDP group. Both groups showed trends towards reduction in investigator and subject rated local tolerability scores.

Conclusion

CDP/BPO gel demonstrated superior efficacy over CDP gel along with acceptable safety and tolerability in Chinese patients with mild to moderate acne.

Clinical Trials.gov number: NCT01915732
Treatment of psoriasis with etanercept: the typical patient profile
Authors: Prinz J.C. , Puig L. , Girolomoni G.
Published: April 2016

The chronic nature of psoriasis means that patients often require lifetime treatment. Over this time, treatment frequently has to be adapted to meet variable demands resulting from changes in life course and life events. Biological drugs used to treat psoriasis vary in their dosing regimens, convenience and flexibility. Dermatologists need to understand which biologic agent is best suited for each individual patient. A wealth of evidence supports the safe and effective use of etanercept, which offers a rapid and sustained response, flexibility of dosing, maintenance of response after dose reduction or interruption, and efficacy against non‐skin manifestations such as psoriatic arthritis. An expert panel met to agree the typical patient profile of a psoriasis patient treated with etanercept, the main benefits of etanercept in psoriasis, and the patient group most likely to benefit from its use. They agreed that flexibility of dosing, the potential to individualize therapy by stopping and starting treatment while maintaining efficacy, and the possibility of cost saving through the use of flexible treatment regimens were important benefits supporting the use of etanercept in many patients with psoriasis.
Migration Kinetics of Ethylene Glycol Monomer from Pet Bottles into Acidic Food Simulant: Effects of Nanoparticle Presence and Matrix Morphology
Authors: Farhoodi Mehdi , Mohammadifar Mohammad Amin , Mousavi Mohammad , Sotudeh‐Gharebagh Rahmat , Emam‐Djomeh Zahra
Published: April 2016

In this study, migration of ethylene glycol from polyethylene terephthalate (PET) bottles (neat PET and PET nanocomposites) into acidic food simulant is investigated. Nanocomposite pellets were prepared by melt blending of PET and TiO2 nanoparticles. The stretch blow molding machine was used to make the preforms and bottles from neat PET and nanocomposites. DSC analyses showed that the presence of nanoparticles at 3 wt % noticeably affected the crystallization temperature, Tc, and the final degree of crystallinity of PET. The incorporation of nanoparticles in the PET matrix leads to a substantial decrease of water vapor permeability. Nanoparticles also decreased the diffusivity of migrants due to the higher degree of crystallinity. The acetic acid samples were stored at 45C for 15 days. Gas chromatography analysis demonstrated that the migration of ethylene glycol from nanocomposite bottles was less than the neat PET. The polymer‐specific parameters (AP values) from mathematical migration models were derived from the experimental data. The diffusion coefficients (DP) based on Piringer's model showed a considerable difference between DP of nanocomposites and neat PET. It was concluded that the migration of monomers from food contact materials considerably depends on the structure of the manufactured packaging plastic.

Practical Applications

Polyethylene terephthalate (PET) nanocomposite pellets containing 3% wt TiO2 nanoparticles were prepared by melt blending and PET bottles were made by injection stretch blow molding. The results showed that incorporation of TiO2 nano‐fillers in PET matrix considerably increased crystallinity and rigidity of PET packaging material and decreased the amorphous region in the polymer matrix. TiO2 nanoparticles with uniform distribution in the polymer matrix created a tortuous path, leading to reduce in monomer migration from packaging material into food simulant. Mathematical model used in this study was a practical tool for better understanding of migration process. Improved barrier properties and lower monomer migration from PET bottles into food could increase the application of PET nanocomposites in food packaging.
Modeling the Effect of Inulin, pH and Storage Time on the Viability of Selected Lactobacillus in a Probiotic Fruity Yogurt Drink Using the Monte Carlo Simulation
Authors: Nikmaram Parang , Mousavi Seyed Mohamad , Kiani Hossein , Emamdjomeh Zahra , Razavi Seyed Hadi , Mousavi Zeinab
Published: April 2016

The effects of pH (5.5, 5.75, 6 and 6.75) and inulin concentration (0, 0.5, 1 and 2%) on the survival of Lactobacillus casei 431 and Lactobacillus acidophilus LA‐5 in pomegranate yogurt drink during 21 days refrigerator storage at 4C were studied. A polynomial multiple regression equation was used in Monte Carlo simulation to predict the probiotic viability. The model fitted well with experimental data (for L. casei R2 = 0.90 and L. acidophilus R2 = 0.96). Also, sensitivity analysis was applied to identify most substantial factors affected the viability. Through the probability distribution, it was demonstrated that L. casei accommodated to manipulation of the environmental conditions (pH and % inulin) while L. acidophilus failed at the end of shelf life and fell down below the critical number of 106 cfu/mL. The Monte Carlo simulation can be a useful device to estimate the amount of viable probiotic bacteria exist in final product.

Practical Applications

In this study, a functional beverage was produced because the viable probiotic cells are known to be beneficial for human body when sufficient amounts (at least 106 cfu/mL) of probiotic bacteria are carried through dairy products. Monte Carlo simulation can be a robust predictive model in practical industrial applications and in research to make reliable statements about the survival/inactivation of probiotic bacteria when the formulation is changed. Also, this tool makes the industries able to determine the best time to consume a probiotic product to uptake adequate amount of useful microorganisms by the end consumer.
Quality in paediatric emergency medicine: Measurement and reporting
Authors: Borland Meredith L , Shepherd Mike
Published: April 2016

There is a clear demand for quality in the delivery of health care around the world; paediatric emergency medicine is no exception to this movement. It has been identified that gaps exist in the quality of acute care provided to children. Regulatory bodies in Australia and New Zealand are moving to mandate the implementation of quality targets and measures. Within the paediatric emergency department (ED), there is a lack of research into paediatric specific indicators. The existing literature regarding paediatric acute care quality measures has been recently summarised, and expert consensus has now been reported. It is clear that there is much work to be performed to generalise this work to ED. We review suggestions from the current literature relating to feasible indicators within the paediatric acute care setting. We propose options to develop a quality ‘scorecard’ that could be used to assist Australian and New Zealand EDs with quality measurement and benchmarking for their paediatric patients.
Training clinicians to care for children in emergency departments
Authors: Rao Arjun , O'Leary Fenton
Published: April 2016

Children account for 22% of presentations to Emergency Departments in Australia, the majority presenting to mixed departments. A diverse group of clinicians looks after these children. In this review, we examine the different techniques and approaches to implementing education curricula and professional development within these emergency departments with a particular focus on bedside teaching, professional coaching, skills maintenance, e‐learning and simulation.
Scoring systems in paediatric emergency care: Panacea or paper exercise?
Authors: Roland Damian , McCaffery Kevin , Davies Ffion
Published: April 2016

Scoring systems to recognise the most ill patients, or those at risk of deterioration, are increasingly utilised in hospitals that look after paediatric inpatients. There have been efforts to implement these systems in emergency and urgent care settings, but they have yet unproven value. This is because the child or young person presenting acutely is a different cohort than the ‘treated’ ward‐based group. The majority of children presenting to emergency and urgent care settings are discharged home, and so, scoring systems need to recognise the most unwell but also assist in safe and appropriate discharge as well as highlighting those patients in need of more senior review. This article explores this conundrum, suggesting how cognitive factors have a role to play, and how scoring systems can have wider effects than just individual patient care.
Promotion and prelacteal feeding of breastmilk substitutes among mothers in Kathmandu Valley, Nepal
Authors: Pries Alissa M. , Huffman Sandra L. , Adhikary Indu , Upreti Senendra Raj , Dhungel Shrid , Champeny Mary , Zehner Elizabeth
Published: April 2016

In 1992, Nepal passed the Mother's Milk Substitutes (Control of Sale and Distribution) Act in order to regulate the sale, distribution and promotion of substitutes for breastmilk within Nepal, in an effort to protect and promote breastfeeding. Helen Keller International, in collaboration with Nepal's Ministry of Health and Population's Child Health Division, implemented a study to assess mothers' exposure to promotions for and utilization of breastmilk substitutes in Kathmandu Valley, Nepal. A health facility‐based, cross‐sectional survey was conducted among 304 mothers being discharged after delivery. Prelacteal feeding of breastmilk substitutes is prevalent (55.9% of mothers, n = 170). Reported recommendations during antenatal checks and after delivery from health professionals to use breastmilk substitutes were prevalent, occurring among 47.4% (n = 144) of mothers; rates of these recommendations were significantly higher for mothers that delivered in private health facilities, as compared with public (67.7% vs. 38.0%, P < 0.001). Mothers that received a recommendation to use a breastmilk substitute from a health worker were 16.7 times more likely to provide a prelacteal feed of a breastmilk substitute, as compared with mothers that did not receive a recommendation (P < 0.001). Few mothers reported observation of commercial advertisements for breastmilk substitutes inside a health facility (reported by 3.6% of mothers). No mothers reported receiving a sample of a breastmilk substitute, bottle or teat from a health professional. More information is needed to determine why there is such a high rate of health worker recommendations for breastmilk substitute use in the first few days after delivery.

Key messages

While utilization of breastmilk substitutes is low among mothers of young children in Nepal, prelacteal feeding of breastmilk substitutes is highly prevalent in Kathmandu Valley.

Reported recommendations from health professionals to use breastmilk substitutes are common (over 40%) and are associated with prelacteal feeding among Nepal mothers included in this study.

Provision of lactation management training to health workers and monitoring their practices regularly could strengthen breastfeeding counselling, aid in reducing high rates of prelacteal feeding and contribute to improved infant feeding practices.
High use of commercial food products among infants and young children and promotions for these products in Cambodia
Authors: Pries Alissa M. , Huffman Sandra L. , Mengkheang Khin , Kroeun Hou , Champeny Mary , Roberts Margarette , Zehner Elizabeth
Published: April 2016

Despite national improvements in child survival, 40% of Cambodian children less than 5 years of age are stunted. Commercially produced complementary foods could be nutritionally beneficial for young children in Cambodia if fortified and of optimal nutrient composition. However, other nutrient‐poor commercially produced snack foods may be detrimental to young child feeding by displacing consumption of other nutritious foods. This study assessed consumption of commercial food products among infants and young children and their mothers' exposure to promotions for these products. A cross‐sectional survey was conducted among 294 mothers of children less than 24 months of age living in Phnom Penh. Of children 6‐23 months of age, 55.0% consumed a commercially produced snack food product on the prior day, and 80.6% had consumed one in the prior week. Only 12 (5.4%) children 6‐23 months of age had consumed a commercially produced complementary food. Almost all mothers (96.9%) had observed a promotion for a commercially produced snack food product, and 29.3% reported observation of a promotion for a commercial complementary food. Only one‐third (32.9%) of children 6‐23 months of age achieved a minimum acceptable diet. Findings indicate that there is a need to improve infant and young child feeding practices among children less than 24 months of age living in Phnom Penh. Nutritious options should be promoted, and consumption of unhealthy commercially produced snack food products should be discouraged.
Point‐of‐sale promotion of breastmilk substitutes and commercially produced complementary foods in Cambodia, Nepal, Senegal and Tanzania
Authors: Champeny Mary , Pereira Catherine , Sweet Lara , Khin Mengkheang , Ndiaye Coly Aminata , Sy Gueye Ndeye Yaga , Adhikary Indu , Dhungel Shrid , Makafu Cecilia , Zehner Elizabeth , Huffman Sandra L.
Published: April 2016

In order to assess the prevalence of point‐of‐sale promotions of infant and young child feeding products in Phnom Penh, Cambodia; Kathmandu Valley, Nepal; Dakar Department, Senegal; and Dar es Salaam, Tanzania, approximately 30 retail stores per site, 121 in total, were visited. Promotional activity for breastmilk substitutes (BMS) and commercially produced complementary foods in each site were recorded. Point‐of‐sale promotion of BMS occurred in approximately one‐third of sampled stores in Phnom Penh and Dakar Department but in 3.2% and 6.7% of stores in Kathmandu Valley and Dar es Salaam, respectively. Promotion of commercially produced complementary foods was highly prevalent in Dakar Department with half of stores having at least one promotion, while promotions for these products occurred in 10% or less of stores in the other three sites. While promotion of BMS in stores is legal in Senegal, it is prohibited in Cambodia without prior permission of the Ministry of Health/Ministry of Information and prohibited in both Nepal and Tanzania. Strengthening legislation in Senegal and enforcing regulations in Cambodia could help to prevent such promotion that can negatively affect breastfeeding practices.

Key messages

Even in countries such as Cambodia, Nepal and Tanzania where point‐of‐sale promotion is restricted, promotions of BMS were observed (in nearly one‐third of stores in Phnom Penh and less than 10% in Dar es Salaam and Kathmandu).

Limited promotion of commercially produced complementary foods was evident (less than 10% of stores had a promotion for such foods), except in Dakar Department, where promotions were found in half of stores.

Efforts are needed to strengthen monitoring, regulation and enforcement of restrictions on the promotion of BMS.

Manufacturers and distributors should take responsibility for compliance with national regulations and global policies pertaining to the promotion of breastmilk substitutes.
Infant and young child feeding practices among children under 2 years of age and maternal exposure to infant and young child feeding messages and promotions in Dar es Salaam, Tanzania
Authors: Vitta Bineti S. , Benjamin Margaret , Pries Alissa M. , Champeny Mary , Zehner Elizabeth , Huffman Sandra L.
Published: April 2016

There are limited data describing infant and young child feeding practices (IYCF) in urban Tanzania. This study assessed the types of foods consumed by children under 2 years of age and maternal exposure to promotions of these foods in Dar es Salaam, Tanzania. A cross‐sectional survey was conducted among 305 mothers of children less than 24 months of age who attended child health services in October and November, 2014. Among infants less than 6 months of age, rates of exclusive breastfeeding were low (40.8%) and a high proportion (38.2%) received semi‐solid foods. Continued breastfeeding among 20–23‐month‐olds was only 33.3%. Consumption of breastmilk substitutes was not prevalent, and only 3.9% of infants less than 6 months of age and 4.8% of 6–23 month‐olds were fed formula. Among 6–23‐month‐olds, only 38.4% consumed a minimum acceptable diet (using a modified definition). The homemade complementary foods consumed by the majority of 6‐23‐month‐olds (85.2%) were cereal‐dominated and infrequently contained micronutrient‐rich ingredients. Only 3.1% of 6–23‐month‐olds consumed commercially produced infant cereal on the day preceding the interview. In contrast, commercially produced snack foods were consumed by 23.1% of 6–23‐month‐olds. Maternal exposure to commercial promotions of breastmilk substitutes and commercially produced complementary foods was low (10.5% and 1.0%, respectively), while exposure to promotions of commercially produced snack foods was high (45.9%). Strategies are needed to improve IYCF practices, particularly with regard to exclusive and continued breastfeeding, increased dietary diversity and consumption of micronutrient‐rich foods, and avoidance of feeding commercially produced snack foods.
Population genomic scans suggest novel genes underlie convergent flowering time evolution in the introduced range of Arabidopsis thaliana
Authors: Gould Billie A. , Stinchcombe John R.
Published: April 2016

A long‐standing question in evolutionary biology is whether the evolution of convergent phenotypes results from selection on the same heritable genetic components. Using whole‐genome sequencing and genome scans, we tested whether the evolution of parallel longitudinal flowering time clines in the native and introduced ranges of Arabidopsis thaliana has a similar genetic basis. We found that common variants of large effect on flowering time in the native range do not appear to have been under recent strong selection in the introduced range. We identified a set of 38 new candidate genes that are putatively linked to the evolution of flowering time. A high degree of conditional neutrality of flowering time variants between the native and introduced range may preclude parallel evolution at the level of genes. Overall, neither gene pleiotropy nor available standing genetic variation appears to have restricted the evolution of flowering time to high‐frequency variants from the native range or to known flowering time pathway genes.
Pharmacological management of IPF
Authors: Borie Raphael , Justet Aurelien , Beltramo Guillaume , Manali Effrosyni D. , Pradère Pauline , Spagnolo Paolo , Crestani Bruno
Published: April 2016

Idiopathic pulmonary fibrosis (IPF) is a deadly disease with a median survival of approximately three years in historical cohorts. Despite increased knowledge of disease pathophysiology and selection of more targeted therapy, main clinical trials yielded negative results. However, two agents, pirfenidone and nintedanib, were recently shown to be effective in IPF and received marketing authorization worldwide. Both drugs significantly reduce functional decline and disease progression with an acceptable safety profile. Yet, none of these drugs actually improves or even stabilizes the disease or the symptoms perceived by the patient. Several other treatments and combinations are currently tested, and many more are ready for clinical trials. Their completion is critical for achieving the ultimate goal of curing patients with IPF.
We Restrict CRRT to Only the Most Hemodynamically Unstable Patients
Authors: Kashani Kianoush , Mehta Ravindra L.
Published: April 2016

From the initial version of an extended renal replacement therapy, the initiative to provide safer, more efficient means for detoxification and volume removal in comparison with intermittent renal replacement therapies (IRRT) has been evaluated. As a result, the Kidney Disease Improving Global Outcomes guidelines for acute kidney injury recommend the preferential use of continuous renal replacement therapy (CRRT) in patients who are hemodynamically unstable or who suffer from intracranial hypertension. The choice of dialysis modality is also influenced by other factors including clinical expertise, and the availability of each treatment option in individual medical centers. In the scientific community, there is an ongoing debate regarding the choice of dialysis modality. On one side, the inability of recent studies to demonstrate any mortality or renal recovery benefit for CRRT, the need for patient immobilization, and prohibitive additional costs impede widespread adoption of the method.On the other side, the physiological advantages of CRRT in detoxification and volume removal and the identified flaws related to the comparative literature regarding CRRT and IRRT fuel this debate. Fluid overload is a recognized and yet clinically underappreciated factor that increases morbidity and mortality in the intensive care unit (ICU). Continuous renal replacement therapy has a distinct advantage over IRRT in achieving euvolemia and thus the potential for improving outcomes in all patients in the ICU setting in which extensive fluid administration is often obligatory. With this in mind, perhaps CRRT should not be restricted to only those patients in whom their hemodynamic status requires it. This article reviews the current literature and the myths that may influence the selection of one mode of therapy over the other among patients requiring renal replacement therapy in the ICU.
Selenium and vitamin E together improve intestinal epithelial barrier function and alleviate oxidative stress in heat‐stressed pigs
Authors: Liu Fan , Cottrell Jeremy J. , Furness John B. , Rivera Leni R. , Kelly Fletcher W. , Wijesiriwardana Udani , Pustovit Ruslan V. , Fothergill Linda J. , Bravo David M. , Celi Pietro , Leury Brian J. , Gabler Nicholas K. , Dunshea Frank R.
Published: April 2016

New Findings

What is the central question of this study?

Oxidative stress may play a role in compromising intestinal epithelial barrier integrity in pigs subjected to heat stress, but it is unknown whether an increase of dietary antioxidants (selenium and vitamin E) could alleviate gut leakiness in heat‐stressed pigs.

What is the main finding and its importance?

Levels of dietary selenium (1.0 p.p.m.) and vitamin E (200 IU kg−1) greater than those usually recommended for pigs reduced intestinal leakiness caused by heat stress. This finding suggests that oxidative stress plays a role in compromising intestinal epithelial barrier integrity in heat‐stressed pigs and also provides a nutritional strategy for mitigating these effects.

Heat stress compromises the intestinal epithelial barrier integrity of mammals through mechanisms that may include oxidative stress. Our objective was to test whether dietary supplementation with antioxidants, selenium (Se) and vitamin E (VE), protects intestinal epithelial barrier integrity in heat‐stressed pigs. Female growing pigs (n = 48) were randomly assigned to four diets containing from 0.2 p.p.m. Se and 17 IU kg−1 VE (control, National Research Council recommended) to 1.0 p.p.m. Se and 200 IU kg−1 VE for 14 days. Six pigs from each dietary treatment were then exposed to either thermoneutral (20°C) or heat‐stress conditions (35°C 09.00–17.00 h and 28°C overnight) for 2 days. Transepithelial electrical resistance and fluorescein isothiocyanate–dextran (4 kDa; FD4) permeability were measured in isolated jejunum and ileum using Ussing chambers. Rectal temperature, respiratory rate and intestinal HSP70 mRNA abundance increased (all P < 0.001), and respiratory alkalosis occurred, suggesting that pigs were heat stressed. Heat stress also increased FD4 permeability and decreased transepithelial electrical resistance (both P < 0.01). These changes were associated with changes indicative of oxidative stress, a decreased glutathione peroxidase (GPX) activity and an increased glutathione disulfide (GSSG)‐to‐glutathione (GSH) ratio (both P < 0.05). With increasing dosage of Se and VE, GPX‐2 mRNA (P = 0.003) and GPX activity (P = 0.049) increased linearly, the GSSG:GSH ratio decreased linearly (P = 0.037), and the impacts of heat stress on intestinal barrier function were reduced (P < 0.05 for both transepithelial electrical resistance and FD4 permeability). In conclusion, in pigs an increase of dietary Se and VE mitigated the impacts of heat stress on intestinal barrier integrity, associated with a reduction in oxidative stress.
The myths and physiology surrounding intrapartum decelerations: the critical role of the peripheral chemoreflex
Authors: Lear Christopher A. , Galinsky Robert , Wassink Guido , Yamaguchi Kyohei , Davidson Joanne O. , Westgate Jenny A. , Bennet Laura , Gunn Alistair J.
Published: April 2016

A distinctive pattern of recurrent rapid falls in fetal heart rate, called decelerations, are commonly associated with uterine contractions during labour. These brief decelerations are mediated by vagal activation. The reflex triggering this vagal response has been variably attributed to a mechanoreceptor response to fetal head compression, to baroreflex activation following increased blood pressure during umbilical cord compression, and/or a Bezold–Jarisch reflex response to reduced venous return from the placenta. Although these complex explanations are still widespread today, there is no consistent evidence that they are common during labour. Instead, the only mechanism that has been systematically investigated, proven to be reliably active during labour and, crucially, capable of producing rapid decelerations is the peripheral chemoreflex. The peripheral chemoreflex is triggered by transient periods of asphyxia that are a normal phenomenon associated with all uterine contractions. This should not cause concern as the healthy fetus has a remarkable ability to adapt to these repeated but short periods of asphyxia. This means that the healthy fetus is typically not at risk of hypotension and injury during uncomplicated labour even during repeated brief decelerations. The physiologically incorrect theories surrounding decelerations that ignore the natural occurrence of repeated asphyxia probably gained widespread support to help explain why many babies are born healthy despite repeated decelerations during labour. We propose that a unified and physiological understanding of intrapartum decelerations that accepts the true nature of labour is critical to improve interpretation of intrapartum fetal heart rate patterns.

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NRF2 activation by antioxidant antidiabetic agents accelerates tumor metastasis
Authors: Wang Hui , Liu Xiufei , Long Min , Huang Yi , Zhang Linlin , Zhang Rui , Zheng Yi , Liao Xiaoyu , Wang Yuren , Liao Qian , Li Wenjie , Tang Zili , Tong Qiang , Wang Xiaocui , Fang Fang , de la Vega Montserrat Rojo , Ouyang Qin , Zhang Donna D. , Yu Shicang , Zheng Hongting
Published: April 2016

Antioxidant antidiabetic drugs may promote tumor metastasis.
Global health partnerships: Are they working?
Authors: Muir Jonathan A. , Farley Jessica , Osterman Allison , Hawes Stephen E. , Martin Keith , Stephen Morrison J. , Holmes King K.
Published: April 2016

An assessment of global health collaborations highlights the advantages of synergies between global health research and training programs.
Can the past predict the future?
Authors: Peñagarikano Olga
Published: April 2016

Maternal immune activation may induce transgenerational transmission of behavioral defects.
CoINcIDE: All together now
Authors: Greene Casey S.
Published: April 2016

Meta-analysis for unsupervised clustering of clinical data empowers scientists to use small data sets for patient subtype discovery.
Metabolic Requirements of Escherichia coli in Intracellular Bacterial Communities during Urinary Tract Infection Pathogenesis
Authors: Conover Matt S. , Hadjifrangiskou Maria , Palermo Joseph J. , Hibbing Michael E. , Dodson Karen W. , Hultgren Scott J.
Published: April 2016

Uropathogenic
Escherichia coli
(UPEC) is the primary etiological agent of over 85% of community-acquired urinary tract infections (UTIs). Mouse models of infection have shown that UPEC can invade bladder epithelial cells in a type 1 pilus-dependent mechanism, avoid a TLR4-mediated exocytic process, and escape into the host cell cytoplasm. The internalized UPEC can clonally replicate into biofilm-like intracellular bacterial communities (IBCs) of thousands of bacteria while avoiding many host clearance mechanisms. Importantly, IBCs have been documented in urine from women and children suffering acute UTI. To understand this protected bacterial niche, we elucidated the transcriptional profile of bacteria within IBCs using microarrays. We delineated the upregulation within the IBC of genes involved in iron acquisition, metabolism, and transport. Interestingly,
lacZ
was highly upregulated, suggesting that bacteria were sensing and/or utilizing a galactoside for metabolism in the IBC. A Δ
lacZ
strain displayed significantly smaller IBCs than the wild-type strain and was attenuated during competitive infection with a wild-type strain. Similarly, a
galK
mutant resulted in smaller IBCs and attenuated infection. Further, analysis of the highly upregulated gene
yeaR
revealed that this gene contributes to oxidative stress resistance and type 1 pilus production. These results suggest that bacteria within the IBC are under oxidative stress and, consistent with previous reports, utilize nonglucose carbon metabolites. Better understanding of the bacterial mechanisms used for IBC development and establishment of infection may give insights into development of novel anti-virulence strategies.

IMPORTANCE
Urinary tract infections (UTIs) are one of the most common bacterial infections, impacting mostly women. Every year, millions of UTIs occur in the U.S. with most being caused by uropathogenic
E. coli
(UPEC). During a UTI, UPEC invade bladder cells and form an intracellular bacterial community (IBC) that allows for the bacteria to replicate protected from the host immune response. In this study, we investigated genes that are expressed by UPEC within the IBC and determined how they contribute to the formation of this specialized community. Our findings suggest that galactose is important for UPEC growth in the IBC. Additionally, we found that a gene involved in oxidative stress is also important in the regulation of a key factor needed for UPEC invasion of bladder cells. These results may open the door for the development of treatments to diminish UTI frequency and/or severity.
Ralstonia solanacearum Type III Effector RipAY Is a Glutathione-Degrading Enzyme That Is Activated by Plant Cytosolic Thioredoxins and Suppresses Plant Immunity
Authors: Mukaihara Takafumi , Hatanaka Tadashi , Nakano Masahito , Oda Kenji
Published: April 2016

The plant pathogen
Ralstonia solanacearum
uses a large repertoire of type III effector proteins to succeed in infection. To clarify the function of effector proteins in host eukaryote cells, we expressed effectors in yeast cells and identified seven effector proteins that interfere with yeast growth. One of the effector proteins, RipAY, was found to share homology with the ChaC family proteins that function as γ-glutamyl cyclotransferases, which degrade glutathione (GSH), a tripeptide that plays important roles in the plant immune system. RipAY significantly inhibited yeast growth and simultaneously induced rapid GSH depletion when expressed in yeast cells. The
in vitro
GSH degradation activity of RipAY is specifically activated by eukaryotic factors in the yeast and plant extracts. Biochemical purification of the yeast protein identified that RipAY is activated by thioredoxin TRX2. On the other hand, RipAY was not activated by bacterial thioredoxins. Interestingly, RipAY was activated by plant
h
-type thioredoxins that exist in large amounts in the plant cytosol, but not by chloroplastic
m
-,
f
-,
x
-,
y
- and
z
-type thioredoxins, in a thiol-independent manner. The transient expression of RipAY decreased the GSH level in plant cells and affected the flg22-triggered production of reactive oxygen species (ROS) and expression of pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) marker genes in
Nicotiana benthamiana
leaves. These results indicate that RipAY is activated by host cytosolic thioredoxins and degrades GSH specifically in plant cells to suppress plant immunity.

IMPORTANCE
Ralstonia solanacearum
is the causal agent of bacterial wilt disease of plants. This pathogen injects virulence effector proteins into host cells to suppress disease resistance responses of plants. In this article, we report a biochemical activity of
R. solanacearum
effector protein RipAY. RipAY can degrade GSH, a tripeptide that plays important roles in the plant immune system, with its γ-glutamyl cyclotransferase activity. The high GSH degradation activity of RipAY is considered to be a good weapon for this bacterium to suppress plant immunity. However, GSH also plays important roles in bacterial tolerance to various stresses and growth. Interestingly, RipAY has an excellent safety mechanism to prevent unwanted firing of its enzyme activity in bacterial cells because RipAY is specifically activated by host eukaryotic thioredoxins. This study also reveals a novel host plant protein acting as a molecular switch for effector activation.
Are parents’ anxiety and depression related to child fussy eating?
Authors: de Barse Lisanne M , Cardona Cano Sebastian , Jansen Pauline W , Jaddoe Vincent V W , Verhulst Frank C , Franco Oscar H , Tiemeier Henning , Tharner Anne
Published: April 2016

Objective

To examine the association between parental anxiety and depression with child fussy eating—that is, consistent rejection of particular food items.

Design

This study was embedded in Generation R, a prospective cohort from fetal life onwards in the Netherlands.

Setting

Population-based.

Participants

4746 4-year-old children and their parents.

Exposure

Parental internalising problems (ie, symptoms of anxiety and depression) were assessed with the Brief Symptoms Inventory during pregnancy and the preschool period (child age 3 years).

Main outcome measure

The food fussiness scale of the Children's Eating Behaviour Questionnaire.

Results

Maternal anxiety during pregnancy and during the child's preschool period was related to higher food fussiness sum-scores in children. For instance, per point on the anxiety scale in pregnancy, children had on average a 1.02 higher sum-score (95% CI 0.59 to 1.46) on the food fussiness scale, after adjustment for confounders. Likewise, mothers’ depressive symptoms at both time points were associated with fussy eating behaviour in their children (eg, in the antenatal period: per point on the depression scale, children had a 0.91 point higher sum-score on the food fussiness scale, 95% CI 0.49 to 1.33). We found largely similar associations between fathers’ internalising problems and children's fussy eating. However, fathers’ anxiety during the antenatal period was not related to child fussy eating.

Conclusions

Maternal and paternal internalising problems were prospectively associated with fussy eating in preschoolers. Healthcare practitioners should be aware that non-clinical symptoms of anxiety and depression in parents are risk factors for child fussy eating.
Unmasking the elusive giant: an unusual case presenting as third nerve palsy in a patient with scleroderma
Authors: Ng Wan Lin , McManus John , Devlin James Anthony Joseph , Fraser Alexander
Published: April 2016

We report a case of an 80-year-old woman being treated with rituximab and maintenance corticosteroids for long-standing scleroderma who presented with right-sided third nerve palsy. Radiological investigations including CT, MRI and MR angiography of the brain were unremarkable. The patient was discharged with a diagnosis of probable microvascular third nerve palsy but was readmitted 1 week later with total visual loss in her left eye. Despite the absence of diagnostic clinical signs, giant cell arteritis (GCA) was suspected, and she was started on intravenous corticosteroids. Left temporal artery biopsy subsequently confirmed histological findings diagnostic of GCA. Unfortunately, she remained blind in the left eye.
A systematic review of technology-based interventions for unintentional injury prevention education and behaviour change
Authors: Omaki Elise , Rizzutti Nicholas , Shields Wendy , Zhu Jeffrey , McDonald Eileen , Stevens Martha W , Gielen Andrea
Published: April 2016

Objective

The aims of this literature review are to (1) summarise how computer and mobile technology-based health behaviour change applications have been evaluated in unintentional injury prevention, (2) describe how these successes can be applied to injury-prevention programmes in the future and (3) identify research gaps.

Methods

Studies included in this systematic review were education and behaviour change intervention trials and programme evaluations in which the intervention was delivered by either a computer or mobile technology and addressed an unintentional injury prevention topic. Articles were limited to those published in English and after 1990.

Results

Among the 44 technology-based injury-prevention studies included in this review, 16 studies evaluated locally hosted software programmes, 4 studies offered kiosk-based programmes, 11 evaluated remotely hosted internet programmes, 2 studies used mobile technology or portable devices and 11 studies evaluated virtual-reality interventions. Locally hosted software programmes and remotely hosted internet programmes consistently increased knowledge and behaviours. Kiosk programmes showed evidence of modest knowledge and behaviour gains. Both programmes using mobile technology improved behaviours. Virtual-reality programmes consistently improved behaviours, but there were little gains in knowledge. No studies evaluated text-messaging programmes dedicated to injury prevention.

Conclusions

There is much potential for computer-based programmes to be used for injury-prevention behaviour change. The reviewed studies provide evidence that computer-based communication is effective in conveying information and influencing how participants think about an injury topic and adopt safety behaviours.
The association between diet and glucocorticoid treatment in patients with SLE
Authors: Lourdudoss Cecilia , Hafström Ingiäld , Frostegård Johan , van Vollenhoven Ronald
Published: April 2016

Background

Some studies suggest that the risk for and severity of systemic lupus erythematosus (SLE) can be modified by certain nutrients. The aim of this study was to investigate the association between diet and glucocorticoid (GC) treatment, as a proxy for disease activity, in patients with SLE.

Methods

We included 111 patients with SLE from the SLE Vascular Impact Cohort (SLEVIC). Dietary data were linked with data on GC treatment during a 2-year period. The association between diet and GC treatment was analysed with logistic regression. GC treatment and unchanged/increased doses were considered a proxy for active SLE.

Results

During the 2-year period, 54 patients (48.6%) had continued GC treatment. Dietary vitamin D was associated with GC treatment (OR=2.70–2.85 (95% CI 1.00 to 8.11)), whereas alcohol was inversely associated with GC treatment (OR=0.28–0.39 (95% CI 0.10 to 98)). Beta-carotene, fatty acid C18:2 and vitamin B6were inversely associated with unchanged/increased GC dose (OR=0.29–0.30 (95% CI 0.10 to 0.90)). Finally, total energy intake was associated with GC doses >5.0 mg/day and >7.5 mg/day, explaining a direct association between 35 nutrients and higher GC dose levels (OR=2.98–23.82 (95% CI 1.01 to 203.88)).

Discussion

Dietary vitamin D did not protect against lupus activity. Beta-carotene, fatty acid C18:2 and vitamin B6may protect against increased GC dose. The inverse association between alcohol intake and GC treatment/lupus activity may provide a partial explanation for the link between moderate alcohol intake and reduced risk of SLE. The association between higher dietary intake and higher GC dose levels indicated GC's influence on increasing appetite.
Complete reperfusion mitigates influence of treatment time on outcomes after acute stroke
Authors: Prabhakaran Shyam , Castonguay Alicia C , Gupta Rishi , Sun Chung-Huan J , Martin Coleman O , Holloway William , Mueller-Kronast Nils H , English Joey , Linfante Italo , Dabus Guilherme , Malisch Tim , Marden Franklin , Bozorgchami Hormozd , Xavier Andrew , Rai Ansaar , Froehler Michael , Badruddin Aamir , Taqi Mohammad Asif , Novakovic Roberta , Abraham Michael , Janardhan Vallabh , Shaltoni Hashem , Yoo Albert J , Abou-Chebl Alex , Chen Peng , Britz Gavin , Kaushal Ritesh , Nanda Ashish , Nogueira Raul , Nguyen Thanh , Zaidat Osama O
Published: April 2016

Background

Time to reperfusion following endovascular treatment (ET) predicts outcomes after acute ischemic stroke (AIS).

Objective

To assess the time–outcome relationship within reperfusion grades in the North American Solitaire Acute Stroke registry.

Methods

We identified patients given ET for anterior circulation ischemic stroke within 8 h from onset and in whom reperfusion was achieved. Together with clinical and outcome data, site-adjudicated modified Thrombolysis in Cerebral Ischemia (TICI) was recorded. We assessed the impact of time to reperfusion (onset to procedure completion time) on good outcome (modified Rankin Scale 0–2 at 3 months) in patients who achieved TICI 2 or higher reperfusion in multivariable models. We further assessed this relationship within strata of reperfusion grades. A p<0.05 was considered significant.

Results

Independent predictors of good outcome at 3 months among those achieving TICI ≥2a reperfusion (n=188) were initial National Institutes of Health Stroke Scale score (adjusted OR=0.90, 95% CI 0.85 to 0.95), symptomatic hemorrhage (adj. OR=0.16, 95% CI 0.05 to 0.60), TICI grade (TICI 3: adj. OR=11.52, 95% CI 3.34 to 39.77; TICI 2b: adj. OR=5.14, 95% CI 1.61 to 16.39), and time to reperfusion per 30 min interval (adj. OR=0.91, 95% CI 0.82 to 0.99). There was an interaction between final TICI grade and 30 min time to reperfusion intervals (p=0.001) such that the effect of time was strongest in TICI 2a patients.

Conclusions

Time to reperfusion was a strong predictor of outcome following ET for AIS. However, the effect varied by TICI grade such that its greatest effect was in those achieving TICI 2a reperfusion.
Brain imaging in dementia
Authors: Bonifacio Guendalina , Zamboni Giovanna
Published: April 2016

The introduction of MRI and positron emission tomography (PET) brain imaging has contributed significantly to the understanding of different dementia syndromes. Over the past 20 years these imaging techniques have been increasingly used for clinical characterisation and differential diagnosis, and to provide insight into the effects on functional capacity of the brain, patterns of spatial distribution of different dementia syndromes and their natural history and evolution over time. Brain imaging is also increasingly used in clinical trials, as part of inclusion criteria and/or as a surrogate outcome measure. Here we review all the relatively specific findings that can be identified with different MRI and PET techniques in each of the most frequent dementing disorders.
Hydraulic behaviour of parallel fibres under longitudinal flow: a numerical treatment
Authors: Nguyen Thanh Trung , Indraratna Buddhima
Published: April 2016

Modelling fluid flow through fibrous porous materials has gained increasing attention from industry and research communities. Analytical and numerical methods are commonly used to predict the hydraulic characteristics of fibrous material during fluid flow, although to date most techniques have been conducted using the same assumption that the geometric features of fibres remain unchanged. In other words, the mutual interaction between fibre elements and fluid is ignored, which undermines the actual working condition of fibres. This paper therefore presents a potential numerical approach that is capable of capturing the behaviour of a fluid–solid system. Individual fibres are simulated by the discrete element method (DEM) coupled with the concept of computational fluid dynamics (CFD), whereby the information contained in each phase is constantly exchanged and updated with other phases. In comparison with conventional solutions, including the Kozeny–Carman (K–C) fluid flow principle and other valid studies, the results show an acceptable agreement in predicting the hydraulic conductivity of a fibrous system. Subjected to laminar longitudinal flow, fibre motion is also evaluated with respect to varying bond stiffness and flow velocity. The study indicates the potential of the proposed technique in modelling drainage and filtration that is based on the hydraulic behaviour of fibrous porous geomaterials.
Pollen DNA barcoding: current applications and future prospects
Authors: Bell Karen L. , de Vere Natasha , Keller Alexander , Richardson Rodney T. , Gous Annemarie , Burgess Kevin S. , Brosi Berry J.
Published: April 2016

Identification of the species origin of pollen has many applications, including assessment of plant–pollinator networks, reconstruction of ancient plant communities, product authentication, allergen monitoring, and forensics. Such applications, however, have previously been limited by microscopy-based identification of pollen, which is slow, has low taxonomic resolution, and has few expert practitioners. One alternative is pollen DNA barcoding, which could overcome these issues. Recent studies demonstrate that both chloroplast and nuclear barcoding markers can be amplified from pollen. These recent validations of pollen metabarcoding indicate that now is the time for researchers in various fields to consider applying these methods to their research programs. In this paper, we review the nascent field of pollen DNA barcoding and discuss potential new applications of this technology, highlighting existing limitations and future research developments that will improve its utility in a wide range of applications.