bluuebunny/crossref_metadata_2025 huggingface dataset:
Variation in avoidable emergency admissions: multiple case studies of emergency and urgent care systems
Authors: O’Cathain Alicia , Knowles Emma , Turner Janette , Hirst Enid , Goodacre Steve , Nicholl Jon
Published: August 2015

Objective

To identify factors affecting variation in avoidable emergency admissions that are not usually identified in statistical regression.

Methods

As part of an ethnographic residual analysis, we compared six emergency and urgent care systems in England, interviewing 82 commissioners and providers of key emergency and urgent care services.

Results

There was variation between the six cases in how interviewees described three parts of their emergency and urgent care systems. First, interviewees’ descriptions revealed variation in the availability of services before patients decided to attend emergency departments. Poor availability of general practice out of hours services in some of the cases reportedly made attendance at emergency departments the easier option for patients. Second, there was variation in how interviewees described patients being dealt with during their emergency department visit in terms of availability of senior review by specialists and in coding practices when patients were at risk of breaching the NHS’s 4-hour waiting time target. Third, there was variability in services described as facilitating discharge home from emergency departments. In some cases, emergency department staff described dealing with multiple agencies in multiple localities outside the hospital, making admission the easier option. In other cases, proactive multidisciplinary rapid assessment teams were described as available to avoid admissions. Perceptions of resources available out of hours and the extent of integration between different health services, and between health and social services, also differed by case.

Conclusions

This comparative case study approach identified further factors that may affect avoidable emergency admissions. Initiatives to improve GP out of hours services, make coding more accurately reflect patient experience, increase senior review in emergency departments, offer proactive multidisciplinary admission avoidance teams, improve the availability of out of hours care in the wider emergency and urgent care system, and increase service integration may reduce avoidable admissions. Evaluation of such initiatives would be necessary before wide-scale adoption.
‘Biohoarding’: treasures not seen, stories not told
Authors: Catchpoole Daniel
Published: August 2015

This article raises the concern that biobanks are failing to realize the expected research and health service outcomes. Rather than biobanking, we have been engaging in ‘biohoarding’, where building a quantifiable collection of tissue samples is the primary basis of the bio-resource. The root cause of ‘biohoarding’ is an ideological and motivational confusion as to the purpose for collecting the tissue in the first place. We have lost sight of the knowledge gain that biobanks should generate. The obligation to prevent ‘biohoarding’ lies not with researchers, funders or managers but with policy makers.
Effect of telemetric monitoring in the first 30 days of continuous positive airway pressure adaptation for obstructive sleep apnoea syndrome – a controlled pilot study
Authors: Frasnelli Matthias , Baty Florent , Niedermann Jolanda , Brutsche Martin H , Schoch Otto D
Published: August 2015

Obstructive sleep apnoea syndrome (OSAS) is characterised by repetitive collapse of the upper airway during sleep. Continuous positive airway pressure (CPAP) applied via a mask is the standard treatment for OSAS. CPAP adherence is crucial in therapy to prevent the deleterious consequences of OSAS. We hypothesised that a combination of supervision by telemetry together with targeted telephone support in the first month of CPAP would increase CPAP adherence and treatment success. A total of 113 OSAS patients followed by telemetry-triggered interventions used the device for 5.3 h/night on 28/30 nights, significantly more than the 110 OSAS patients in the control group with 4.6 h/night and 27/30 nights. Telemetry-triggered interventions have a significant impact on adherence rate in early CPAP treatment. These results can be reached with an acceptable additional effort.
Anterior Resection for Rectal Cancer and Visceral Blood Flow: An Explorative Study
Authors: Rutegård M. , Hassmén N. , Hemmingsson O. , Haapamäki M. M. , Matthiessen P. , Rutegård J.
Published: August 2015

Background and Aims:

Impaired blood perfusion may be implicated in anastomotic leakage after anterior resection for rectal cancer. We investigated whether high ligation of the inferior mesenteric artery or total mesorectal excision compromises visceral blood flow in the colonic limb and the rectal stump, respectively.

Material and Methods:

A prospective cohort study was conducted in a university hospital setting. We used Laser Doppler flowmetry to evaluate the impact of level of tie on colonic limb perfusion and the extent of the mesorectal excision on the rectal blood flow. In the rectum, different quadrants were also assessed. The Mann–Whitney U test was used to compare mean blood flow ratios between groups.

Results:

Some 23 patients were recruited in a convenience sample during a period in 2012–2013. The mean blood flow ratio was not decreased after high tie compared to low tie surgery (1.71 vs 1.19; p = 0.28). Total mesorectal excision reduced the mean blood flow ratio in the rectum, as compared with partial mesorectal excision (0.76 vs 1.28; p = 0.14). This was especially pronounced in the posterior aspect of the rectum (0.66 vs 1.68; p = 0.02).

Conclusion:

High tie ligation did not seem to decrease colonic limb perfusion, while total mesorectal excision may decrease rectal blood flow. The posterior quadrant of the rectum might be particularly vulnerable to the dissection involved in total mesorectal excision.
Assessing the Influence of a 360-degree Marketing Communications Campaign With 360-degree Feedback
Authors: Deshpande Sameer , Bhanot Anurudra , Maknikar Sudhir
Published: August 2015

Marketers realize the importance of 360-degree communication (reaching audience members in consistent but multiple ways) to improve brand salience, increase the effectiveness of behavior change strategies, and achieve organizational objectives. While several social marketing organizations have embraced the 360-degree approach, their effectiveness has not been adequately captured by research approaches such as 360-degree feedback. Our study addresses this gap by reporting the influence of Project Raksha (“protection” in Hindi), launched in November 2007 in the rural areas of four Indian states by Pathfinder International in support of government of India’s efforts to reduce maternal mortality and morbidity by promoting institutionalized delivery. The project designed specific interventions at the household, community, local government, and clinical levels to address four types of delays in response to obstetric complications. Westat India carried out postintervention-only evaluation by conducting self-report surveys and interviews with women and their influencers, community health workers, health service providers, and local government members. Findings revealed that most interventions proved effective in addressing the four types of delay that were key contributors to maternal mortality in the project areas. The 360-degree feedback mechanism allowed the social marketing organization to obtain a comprehensive grasp of its persuasion efforts. Achievements and failures were better captured and lessons better learned for future behavior change attempts.
How Do Cooks Actually Cook Vegetables? A Field Experiment With Low-Income Households
Authors: Clarke Peter , Evans Susan H.
Published: August 2015

Vegetables in the diet contribute to disease prevention. However, low-income households underconsume fresh vegetables, perhaps because of cost and of unavailability at nearby stores. A third reason may lurk behind those barriers: cooks’ unfamiliarity with various and appealing ways to prepare vegetables. To illuminate that possibility and to suggest interventions that could be designed more effectively to boost vegetable consumption, this study took the novel step of providing ample, if temporary, supplies of a fresh vegetable to random sets of clients of food pantries. A week later, telephone interviews obtained details about preparations of meals and snacks that household cooks had made with their unexpected bounty. Among the experiment’s 10 vegetables, some were used twice as often as others. Even more striking, cooks practiced a narrow repertoire of preparation methods, dominated by boiling and steaming, across most of the vegetables. Fats and salt were often added to boiled and steamed preparations. Implications are drawn to suggest kinds of recipes—pairings of vegetables and of vegetables with underused means of preparation—that could expand cooks’ repertoires and add variety in flavors, appearances of dishes, meal textures, and aromas.
A Natural Experiment to Determine the Crowd Effect Upon Home Court Advantage
Authors: Boudreaux Christopher J. , Sanders Shane D. , Walia Bhavneet
Published: August 2015

Spectator effects represent a central concept in (behavioral) sports economics. A thorough understanding of the phenomenon promises to further our understanding as to the nature of performance production under pressure. In traditional home advantage studies, it is difficult to isolate the net crowd effect upon relative team performance. In a typical sports setting, multiple factors change at once for a visiting team. Experimental evidence suggests that supportive crowds may hinder task performance. In that it serves as home stadium to two National Basketball Association teams, the Staples Center in Los Angeles offers a rare natural experiment through which to isolate the crowd effect upon competitive output. Each team possesses equivalent familiarity with built environment, and teams face similarly sparse travel demands prior to games between one another. However, the team designated as “home team” in a contest enjoys a largely sympathetic crowd due primarily to season ticket sales. Moreover, crowd effects are sizable in motivating a home team win, raising the likelihood of such an event by between an estimated 21 and 22.8 percentage points. The point estimate implies that essentially the entire home advantage between the two teams is attributable to the crowd effect.
Polyacrylonitrile/polyaniline composite nano/microfiber webs produced by different dopants and solvents
Authors: Kizildag Nuray , Ucar Nuray , Onen Aysen , Karacan Ismail
Published: August 2015

In the present study, the effects of different dopants such as camphorsulfonic acid (CSA), dodecylbenzene sulfonic acid (DBSA) (70 wt% in isopropanol), and dodecylbenzene sulfonic acid sodium salt (DBSANa+), and different solvents such as N-methylpyrrolidone (NMP), and N,N-dimethylformamide (DMF) on the structure and properties of polyacrylonitrile (PAN)/polyaniline (PANI) composite nano/microfiber web produced by the electrospinning technique have been investigated and compared to each other. It has been observed that the nano/microfibers produced from NMP solvent generally had larger fiber diameters than the nano/microfibers produced from DMF, while the use of DBSANa+ resulted in the formation of larger diameters in comparison to other dopants. The use of NMP as the solvent resulted in higher breaking stress values for the reference samples and the composite samples, which contained CSA-doped PANI while the samples that contained DBSA(iso) and DBSANa+-doped PANI showed lower breaking stress values when electrospun from NMP. While the solutions prepared using DBSANa+ showed higher solution conductivities, the use of NMP as the solvent resulted in lower solution conductivity values. Higher conductivity values were obtained with CSA in NMP and with DBSA(iso) in DMF. The conductivity values of the composite nano/microfiber webs were around 10−8 and 10−9 S/cm, which is the range for antistatic materials instead of insulator materials as pure PAN.
Electrophysiological Correlates of Aberrant Motivated Attention and Salience Processing in Unaffected Relatives of Schizophrenia Patients
Authors: Andersen Elizabeth H. , Campbell Alana M. , Schipul Sarah E. , Bellion Carolyn M. , Donkers Franc C. L. , Evans Anna M. , Belger Aysenil
Published: August 2015

Patients with schizophrenia (SCZ) exhibit debilitating deficits in attention and affective processing, which are often resistant to treatment and associated with poor functional outcomes. Impaired orientation to task-relevant target information has been indexed by diminished P3b event-related potentials in patients, as well as their unaffected first-degree relatives, suggesting that P3b may be a vulnerability marker for schizophrenia. Despite intact affective valence processing, patients are unable to employ cognitive change strategies to reduce electrophysiological responses to aversive stimuli. Less is known about the attentional processing of emotionally salient task-irrelevant information in patients and unaffected first-degree relatives. The goal of the present study was to examine the neural correlates of salience processing, as indexed by the late positive potential (LPP), during the processing of emotionally salient distractor stimuli in 31 patients with SCZ, 28 first-degree relatives, and 47 control participants using an oddball paradigm. Results indicated that despite intact novelty detection (P3a), both SCZ and first-degree relatives demonstrated deficiencies in attentional processing, reflected in attenuated target-P3b, and aberrant motivated attention, with reduced early-LPP amplitudes for aversive stimuli relative to controls. First-degree relatives revealed a unique enhancement of the late-LPP response, possibly underlying an exaggerated evaluation of salient information and a compensatory engagement of neural circuitry. Furthermore, reduced early-LPP and target-P3b amplitudes were associated with enhanced symptom severity. These findings suggest that, in addition to P3b, LPP may be useful for monitoring clinical state. Future studies will explore the value of P3 and LPP responses as vulnerability markers for early detection and prediction of psychopathology.
Brain Network Connectivity and Topological Analysis During Voluntary Arm Movements
Authors: Storti Silvia Francesca , Formaggio Emanuela , Manganotti Paolo , Menegaz Gloria
Published: August 2015

Functional connectivity estimates the temporal synchrony among functionally homogeneous brain regions based on the assessment of the dynamics of topologically localized neurophysiological responses. The aim of this study was to investigate task-related changes in brain activity and functional connectivity by applying different methods namely event-related desynchronization (ERD), coherence, and graph-theoretical analysis to electroencephalographic (EEG) recordings, for comparing their respective descriptive power and complementarity. As it is well known, ERD provides an estimate of differences in power spectral densities between active (or task) and rest conditions, functional connectivity allows assessing the level of synchronization between the signals recorded at different scalp locations and graph analysis enables the estimation of the functional network features and topology. EEG activity was recorded on 10 subjects during left/right arm movements. The theta, alpha, and beta bands were considered. Conventional analysis showed a significant ERD in both alpha and beta bands over the sensorimotor cortex during the left arm movement and in beta band during the right arm movement, besides identifying the regions involved in the task, as it was expected. On the other hand, connectivity assessment highlighted that stronger connections are those that involved the motor regions for which graph analysis revealed reduced accessibility and an increased centrality during the movement. Jointly, the last two methods allow identifying the cortical areas that are functionally related in the active condition as well as the topological organization of the functional network. Results support the hypothesis that network analysis brings complementary knowledge with respect to established approaches for modeling motor-induced functional connectivity and could be profitably exploited in clinical contexts.
Underreporting in Psychology Experiments
Authors: Franco Annie , Malhotra Neil , Simonovits Gabor
Published: August 2015

Many scholars have raised concerns about the credibility of empirical findings in psychology, arguing that the proportion of false positives reported in the published literature dramatically exceeds the rate implied by standard significance levels. A major contributor of false positives is the practice of reporting a subset of the potentially relevant statistical analyses pertaining to a research project. This study is the first to provide direct evidence of selective underreporting in psychology experiments. To overcome the problem that the complete experimental design and full set of measured variables are not accessible for most published research, we identify a population of published psychology experiments from a competitive grant program for which questionnaires and data are made publicly available because of an institutional rule. We find that about 40% of studies fail to fully report all experimental conditions and about 70% of studies do not report all outcome variables included in the questionnaire. Reported effect sizes are about twice as large as unreported effect sizes and are about 3 times more likely to be statistically significant.
Solving the fever mystery: Fever and tonsillar ulcer in an elderly patient
Authors: Chung Jasmine Shimin , Lao Zhentang , Tan Ban Hock
Published: August 2015

Pyrexia of unknown origin in the elderly is not an uncommon clinical problem. In day to day clinical practice, it has been observed that antibiotics are often empirically escalated to ‘treat fever’ in an otherwise well patient. However, this may not be warranted. It is more important that a comprehensive history, detailed physical examination and a systematic evaluation be undertaken to identify the cause so that definitive therapy may be administered. Apart from infection, neoplastic and connective tissue disorders are other common causes of pyrexia of unknown origin which should be considered. We describe our approach for evaluating an 80-year-old man who presented with fever and sore throat.
Factors Influencing Quality of Life among People Living with HIV in Coastal South India
Authors: Arjun Banagi Yathiraj , Unnikrishnan Bhaskaran , Ramapuram John T. , Thapar Rekha , Mithra Prasanna , Kumar Nithin , Madi Deepak , Kulkarni Vaman , Holla Ramesh , Darshan Bhagawan
Published: August 2015

Background:

Antiretroviral therapy (ART) has increased life expectancy of HIV/AIDS patients, but the quality of life (QOL) still remains the same.

Methods:

In this cross-sectional study, 356 people living with HIV (PLHIV) were interviewed to assess their QOL using WHOQOL-HIV BREF questionnaire. The association between QOL with sociodemographic, clinical and cohabitation status of the participants was tested using ANOVA and Student t-test, and p value < .05 was considered statistically significant.

Results:

Physical domain of QOL showed maximum score of 16.4, while a minimum score of 12.2 was seen in social relationship domain. Participants with higher socioeconomic status (SES) and self-motivated to take ART had shown better scores across all the domains of QOL ( p < .05).

Conclusion:

In our study, quality of life was high among males, younger patients, married participants, higher socioeconomic status, longer duration of ART, self-motivation to take ART, absence of opportunistic infection, and with higher CD4 count.
Critique of Glenn on Settler Colonialism and Bonilla-Silva on Critical Race Analysis from Indigenous Perspectives
Authors: Fenelon James V.
Published: August 2015

I critique Glenn’s article on settler colonialism and Bonilla-Silva’s article on critical race analysis from Indigenous perspectives, including racial genocide and world-systems analysis, to cover five centuries of global systemic racism during the conquest of the Americas, by Spanish and English colonizers and United States imperialism. I also propose macro-structural, comparative-historical analysis of racism including the destruction, resistance, and revitalization of Native Nations and American Indians.
Stem cell therapy: a novel treatment option for cerebral malaria?
Authors: Wang Wei , Qian Hui , Cao Jun
Published: August 2015

Cerebral malaria, a severe form of the disease, is one of the most severe complications of infection with Plasmodium parasites and a leading cause of malaria mortality. Currently available antimalarial therapy has proven insufficient to prevent neurological complications and death in all cases of cerebral malaria. Souza and colleagues observed that transplantation of bone marrow-derived mesenchymal stromal cells (BM-MSCs) increased survival, reduced parasitemia, decreased malaria pigment accumulation in the spleen, liver and kidney, elevated Kupffer cell count in liver, alleviated renal injury and lung inflammation, and improved lung mechanics in an experimental mouse model of cerebral malaria. Although plenty of challenges lie ahead, their findings show the promise of BM-MSC therapy for the treatment of cerebral malaria.
Time evolution of face recognition in accessible scenarios
Authors: Blanco-Gonzalo Ramon , Poh Norman , Wong Rita , Sanchez-Reillo Raul
Published: August 2015

Up to now, biometric recognition
has shown significant advantages as to be considered a reliable solution for security systems in mobile environments. Nevertheless, due to the short lifetime of biometrics in mobile devices, a handful of concerns regarding usability and accessibility need to be covered in order to meet users’ requirements. This work is focused on analysing the usability and accessibility of a face recognition system used by visually impaired people, focusing on the time spent in the process, which is a critical aspect. Specifically, we cover different key questions including which kind of feedback is more useful for visually impaired users and beneficial for performance and how is the performance evolution in contrast with the time spent in the recognition. Our findings suggest that several parameters improve along with the time spent in the process, including performance. The audio feedback provided in real time involves also better performance and user experience than instructions given previously.
Relationship between family meal frequency and individual dietary intake among diabetic patients
Authors: Ruhee Divya , Mahomoodally Fawzi
Published: August 2015

Background

Notoriously, the island of Mauritius has one of the highest prevalence of diabetes in the world. Management of the disease is very important and family meals are undoubtedly beneficial to patients as they promote the development of healthy eating behaviours and food choices. This study has aimed to probe into potential relationship(s) between family meal frequency and individual dietary intake among diabetic patients and to establish whether family cohesion may be a plausible mediator of this relationship.

Methods

A cross-sectional survey was carried out with a random sample of 384 diabetic patients. The Family Adaptability and Cohesion Evaluation Scale III was used to obtain information on two general aspects of family functioning, that is, cohesiveness and adaptability. Chi-squared (χ2) tests, independent sample t-tests and one-way ANOVA were used to determine statistical significance. Pearson correlation was used to examine associations between family meal frequency, individual dietary intake and family cohesion. Hierarchical linear regression models were performed for the mediation analysis.

Results

Family meal frequency (breakfast, lunch and dinner) was observed to be positively associated with intake of fish, raw vegetables, dried and fresh fruits, low-fat milk, cheese, yogurt, nuts and light butter and negatively associated with intake of red meat, white rice, white bread, whole egg fried, chocolates, fried cakes, burgers, chips, and fried noodles/rice. Average mediation (52.6 %) was indicated by family cohesion for the association between family meal frequency and individual dietary intake among diabetic patients. Sobel’s test further confirmed the trend towards complete mediation (z = 15.4; P < 0.05).

Conclusions

A strong relationship between family meal frequency and individual dietary intake among diabetic patients was recorded. The present study is one of the few studies that have examined family cohesion as a mediator of the relationship and to our best knowledge is the first work to demonstrate a trend towards complete mediation. Results obtained can be used by health professionals to devise strategies for increasing knowledge and awareness of both diabetic patients and their respective families to curd down this public health burden.
Carcinogenic effects of circadian disruption: an epigenetic viewpoint
Authors: Salavaty Adrian
Published: August 2015

Circadian rhythms refer to the endogenous rhythms that are generated to synchronize physiology and behavior with 24-h environmental cues. These rhythms are regulated by both external cues and molecular clock mechanisms in almost all cells. Disruption of circadian rhythms, which is called circadian disruption, affects many biological processes within the body and results in different long-term diseases, including cancer. Circadian regulatory pathways result in rhythmic epigenetic modifications and the formation of circadian epigenomes. Aberrant epigenetic modifications, such as hypermethylation, due to circadian disruption may be involved in the transformation of normal cells into cancer cells. Several studies have indicated an epigenetic basis for the carcinogenic effects of circadian disruption. In this review, I first discuss some of the circadian genes and regulatory proteins. Then, I summarize the current evidence related to the epigenetic modifications that result in circadian disruption. In addition, I explain the carcinogenic effects of circadian disruption and highlight its potential role in different human cancers using an epigenetic viewpoint. Finally, the importance of chronotherapy in cancer treatment is highlighted.
Independent simultaneous source acquisition and processing
Authors: Abma Ray , Howe David , Foster Mark , Ahmed Imtiaz , Tanis Mehmet , Zhang Qie , Arogunmati Adeyemi , Alexander Gino
Published: August 2015

Seismic surveys are often constrained by the time needed to activate all the required sources so the source signals do not interfere with each other. Simultaneous source seismic acquisition, also referred to as blended acquisition, is an effective method for reducing the cost and improving the quality of seismic surveys by eliminating the requirement that the sources do not interfere with each other. Independent simultaneous shooting is a unique form of blended acquisition in which sources operate independently of each other and the receiver recording is continuous. This acquisition method is particularly efficient and robust in obtaining high-density source grids for land and marine surveys. Processing the simultaneous source data depends on the randomness of the shot times to create a situation where the signal is coherent, and the interference is random in common-receiver gathers. Although the older and simpler method of separating interfering shots with random noise attenuation works well when the residual interference noise left by the random noise attenuation is acceptable, higher separation quality is possible using a shot separation process based on sparse inversion and compressive sensing methodology. We found that the resulting simultaneous source surveys produced images that were equivalent to or better than conventional seismic surveys, while requiring less acquisition effort, thus reducing costs.
Elevated C-reactive protein and late-onset bipolar disorder in
78 809 individuals from the general population
Authors: Wium-Andersen Marie Kim , Ørsted David Dynnes , Nordestgaard Børge Grønne
Published: August 2015

Background

No prospective studies have examined the role of C-reactive protein (CRP)
in late-onset bipolar disorder.

Aims

We tested the hypothesis that elevated levels of CRP are associated
cross-sectionally and prospectively with late-onset bipolar disorder, and
that such an association possibly is causal.

Method

We performed cross-sectional and prospective analyses with a median
follow-up time of 5.9 years (interquartile range: 4.4– 7.6) in 78 809
individuals from the general population, and used genetic variants
influencing CRP levels to perform a Mendelian randomisation study.

Results

Elevated levels of CRP were associated both cross-sectionally and
prospectively with late-onset bipolar disorder. When CRP was on a
continuous scale, a doubling in CRP yielded an observational odds ratio
for late-onset bipolar disorder of 1.28 (1.08–1.52) with a corresponding
causal odds ratio of 4.66 (0.89–24.3).

Conclusion

Elevated CRP is associated with increased risk of late-onset bipolar
disorder in the general population which was supported by the genetic
analysis.
GLP-1 Increases Preovulatory LH Source and the Number of Mature Follicles, As Well As Synchronizing the Onset of Puberty in Female Rats
Authors: Outeiriño-Iglesias Verónica , Romaní-Pérez Marina , González-Matías Lucas C. , Vigo Eva , Mallo Federico
Published: August 2015

Control of estrous cycle and reproductive capacity involves a large number of central and peripheral factors, integrating numerous nutritional and metabolic signals. Here we show that glucagon-like peptide-1 (GLP-1), a peptide with anorexigenic and insulinotropic actions, and the GLP-1 receptor agonist Exendin-4 (Ex4) exert a regulatory influence on the gonadal axis, in both adult and prepubertal female rats. In adult rats, Glp-1 receptor expression varies during the estrous cycle at the hypothalamus, pituitary, and ovary. Furthermore, acute treatment with GLP-1 in the morning proestrus doubled the amplitude of the preovulatory LH surge, as well as influencing estradiol and progesterone levels along the estrous cycle. These changes provoked an important increase in the number of Graafian follicles and corpora lutea, as well as in the litter size. Conversely, Ex4 diminished the levels of LH, later producing a partial blockade at the preovulatory surge, yet not affecting either the number of mature follicles or corpora lutea. Chronic administration of low doses of GLP-1 to prepubertal rats synchronized vaginal opening and increased LH levels on the 35th day of life, yet at these doses it did not modify their body weight, food intake, or ovarian and uterine weight. By contrast, chronic exposure to Ex4 produced a significant reduction in ovarian and uterine weight, and serum LH, and the animals treated chronically with Ex4 showed no vaginal opening in the period studied. Overall, our results demonstrate that GLP-1 and Ex4 act on the gonadal axis, involving the hypothalamic kisspeptin system, to influence reproductive efficiency in female rats.
Heme Oxygenase-1 Induction Prevents Autoimmune Diabetes in Association With Pancreatic Recruitment of M2-Like Macrophages, Mesenchymal Cells, and Fibrocytes
Authors: Husseini Mahmoud , Wang Gen-Sheng , Patrick Christopher , Crookshank Jennifer A. , MacFarlane Amanda J. , Noel J. Ariana , Strom Alexander , Scott Fraser W.
Published: August 2015

Immunoregulatory and regenerative processes are activated in the pancreas during the development of type 1 diabetes (T1D) but are insufficient to prevent the disease. We hypothesized that the induction of cytoprotective heme oxygenase-1 (HO-1) by cobalt protophoryrin (CoPP) would prevent T1D by promoting anti-inflammatory and pro-repair processes. Diabetes-prone BioBreeding rats received ip CoPP or saline twice per week for 3 weeks, starting at 30 days and were monitored for T1D. Immunohistochemistry, confocal microscopy, quantitative RT-PCR, and microarrays were used to evaluate postinjection pancreatic changes at 51 days, when islet inflammation is first visible. T1D was prevented in CoPP-treated rats (29% vs 73%). Pancreatic Hmox1 was up-regulated along with islet-associated CD68+HO-1+cells, which were also observed in a striking peri-lobular interstitial infiltrate. Most interstitial cells expressed the mesenchymal marker vimentin and the hematopoietic marker CD34. Spindle-shaped, CD34+vimentin+ cells coexpressed collagen V, characteristic of fibrocytes. M2 macrophage factors Krüppel-like factor 4, CD163, and CD206 were expressed by interstitial cells, consistent with pancreatic upregulation of several M2-associated genes. CoPP upregulated islet-regenerating REG genes and increased neogenic REG3β+ and insulin+ clusters. Thus, short-term induction of HO-1 promoted a protective M2-like milieu in the pancreas and recruited mesenchymal cells, M2 macrophages, and fibrocytes that imparted immunoregulatory and pro-repair effects, preventing T1D.
Anti-Müllerian Hormone Is a Marker for Chemotherapy-Induced Testicular Toxicity
Authors: Levi Mattan , Hasky Noa , Stemmer Salomon M. , Shalgi Ruth , Ben-Aharon Irit
Published: August 2015

Due to increased numbers of young cancer patients and improved survival, the impact of anticancer treatments on fertility has become a major health concern. Despite mounting research on ovarian toxicity, there is paucity of data regarding reliable biomarkers of testicular toxicity. Our aim was to evaluate anti-Müllerian hormone (AMH) as a marker for chemotherapy-induced testicular toxicity. Serum AMH and a panel of gonadal hormones were measured in male cancer patients at baseline and after chemotherapy. In the preclinical setting, mice were injected with diverse chemotherapies and were killed 1 week or 1, 3, or 6 months later. We evaluated spermatogenesis by AMH as well as qualitative and quantitative sperm parameters. Nineteen patients were enrolled, the median age was 38 years (21–44 y). Serum AMH was correlated with increased FSH and T and decreased inhibin-B in gonadotoxic protocols (cisplatin or busulfan) and remained unchanged in nongonadotoxic protocols (capecitabine). AMH expression had the same pattern in mice serum and testes; it was negatively correlated with testicular/epididymal weight and sperm motility. The increase in testicular AMH expression was also correlated with elevated apoptosis (terminal transferase-mediated deoxyuridine 5-triphosphate nick-end labeling) and reduced proliferation (Ki67, proliferating cell nuclear antigen; all seminiferous tubules cells were analyzed). Severely damaged mice testes demonstrated a marked costaining of AMH and GATA-4, a Sertoli cell marker; staining that resembled the pattern of the Sertoli cell-only condition. Our study indicates that the pattern of serum AMH expression, in combination with other hormones, can delineate testicular damage, as determined in both experimental settings. Future large-scale clinical studies are warranted to further define the role of AMH as a biomarker for testicular toxicity.
The Posterodorsal Medial Amygdala Regulates the Timing of Puberty Onset in Female Rats
Authors: Li X. F. , Hu M. H. , Hanley B. P. , Lin Y. S. , Poston L. , Lightman S. L. , O'Byrne K. T.
Published: August 2015

Obesity is the major risk factor for early puberty, but emerging evidence indicates other factors including psychosocial stress. One key brain region notable for its role in controlling calorie intake, stress, and behavior is the amygdala. Early studies involving amygdala lesions that included the medial nucleus advanced puberty in rats. More recently it was shown that a critical site for lesion-induced hyperphagia and obesity is the posterodorsal subnucleus of the medial amygdala (MePD), which may explain the advancement of puberty. Glutamatergic activity also increases in the MePD during puberty without a corresponding γ-aminobutyric acid (GABA)ergic change, suggesting an overall activation of this brain region. In the present study, we report that neurotoxic lesioning of the MePD advances puberty and increases weight gain in female rats fed a normal diet. However, MePD lesioned rats fed a 25% nonnutritive bulk diet also showed the dramatic advancement of puberty but without the increase in body weight. In both dietary groups, MePD lesions resulted in an increase in socialization and a decrease in play fighting behavior. Chronic GABAA receptor antagonism in the MePD from postnatal day 21 for 14 days also advanced puberty, increased socialization, and decreased play fighting without altering body weight, whereas glutamate receptor antagonism delayed puberty and decreased socialization without affecting play fighting. In conclusion, our results suggest the MePD regulates the timing of puberty via a novel mechanism independent of change in body weight and caloric intake. MePD glutamatergic systems advance the timing of puberty whereas local GABAergic activation results in a delay.
Surgery-Induced Weight Loss Is Associated With the Downregulation of Genes Targeted by MicroRNAs in Adipose Tissue
Authors: Ortega Francisco J. , Mercader Josep M. , Moreno-Navarrete José M. , Nonell Lara , Puigdecanet Eulàlia , Rodriquez-Hermosa José I. , Rovira Oscar , Xifra Gemma , Guerra Ester , Moreno María , Mayas Dolores , Moreno-Castellanos Natalia , Fernández-Formoso José A. , Ricart Wifredo , Tinahones Francisco J. , Torrents David , Malagón María M. , Fernández-Real José M.
Published: August 2015

Context:

Molecular mechanisms associated with physiological variations in adipose tissue (AT) are not fully recognized. The most recent reports highlight the critical relevance of microRNAs (miRNAs) found in AT.

Objective:

To identify changes in messenger RNA (mRNA) and miRNA expressions and their interaction in human AT before and after surgery-induced weight loss.

Research Design and Setting:

Genome-wide mRNA and miRNA expressions were assessed by microarrays in abdominal subcutaneous AT of 16 morbidly obese women before and 2 years after laparoscopic Roux-en-Y gastric bypass. The association of changes in miRNAs with their respective mRNA targets was studied. The results were replicated in publicly available microarray datasets. Validation was made by real-time polymerase chain reaction in additional fat samples from 26 age-matched lean women and in isolated human adipocytes.

Results:

A total of 5018 different mRNA probe sets and 15 miRNAs were differentially expressed after surgery-induced weight loss. The clustering of similar expression patterns for gene products with related functions revealed molecular footprints that elucidate significant changes in cell cycle, development, lipid metabolism, and the inflammatory response. The participation of inflammation was demonstrated by results assessed in isolated adipocytes. Interestingly, when transcriptomes were analyzed taking into account the presence of miRNA target sites, miRNA target mRNAs were upregulated in obese AT (P value = 2 × 10−181) and inflamed adipocytes (P value = 4 × 10−61), according to the number of target sites harbored by each transcript.

Conclusions:

Current findings suggest impaired miRNA target gene expression in obese AT in close association with inflammation, both improving after weight loss.
Interplay among transcription factors Ets21c, Fos and Ftz-F1 drives JNK-mediated tumor malignancy
Authors: Külshammer Eva , Mundorf Juliane , Kilinc Merve , Frommolt Peter , Wagle Prerana , Uhlirova Mirka
Published: August 2015

Cancer initiation and maintenance of the transformed cell state depend on altered cellular signaling and aberrant activities of transcription factors (TFs) that drive pathological gene expression in response to cooperating genetic lesions. Deciphering the roles of interacting TFs is therefore central to understanding carcinogenesis and for designing cancer therapies. Here, we use an unbiased genomic approach to define a TF network that triggers an abnormal gene expression program promoting malignancy of clonal tumors, generated in Drosophila imaginal disc epithelium by gain of oncogenic Ras (RasV12) and loss of the tumor suppressor Scribble (scrib1). We show that malignant transformation of the rasV12scrib1 tumors requires TFs of distinct families, namely the bZIP protein Fos, the ETS-domain factor Ets21c, and the nuclear receptor Ftz-F1, all acting downstream of Jun-N-terminal kinase (JNK). Depleting any of the three TFs improves viability of tumor bearing larvae, and this positive effect can be further enhanced by their combined removal. Although both Fos and Ftz-F1 synergistically contribute to rasV12scrib1 tumor invasiveness only Fos is required for JNK-induced differentiation defects and Matrix metalloprotease (MMP1) upregulation. In contrast, the Fos-dimerizing partner Jun is dispensable for JNK to exert its effects in rasV12scrib1 tumors. Interestingly, Ets21c and Ftz-F1 are transcriptionally induced in these tumors in a JNK- and Fos-dependent manner, thereby demonstrating a hierarchy within the tripartite TF network with Fos acting as the most upstream JNK effector. Of the three TFs, only Ets21c can efficiently substitute for loss of polarity and cooperate with RasV12 in inducing malignant clones that, like rasV12scrib1 tumors, invade other tissues and overexpress MMP1 and the Drosophila insulin-like peptide 8 (Dilp8). While rasV12ets21c tumors require JNK for invasiveness, the JNK activity is dispensable for their growth. In conclusion, our study delineates both unique and overlapping functions of distinct TFs that cooperatively promote aberrant expression of target genes, leading to malignant tumor phenotypes.
Transient alteration of the vestibular calyceal junction and synapse in response to chronic ototoxic insult in rats.
Authors: Sedó-Cabezón Lara , Jedynak Paulina , Boadas-Vaello Pere , Llorens Jordi
Published: August 2015

Ototoxicity is known to cause permanent loss of vestibule function through degeneration of sensory hair cells (HCs). However, functional recovery has been reported at times during washout after chronic ototoxicity, although the mechanisms underlying this reversible dysfunction are unknown. Here we study this question in rats chronically exposed to the ototoxic compound 3,3'-iminodipropionitrile (IDPN). Pronounced alterations in vestibular function appeared before significant loss of HCs or stereociliary coalescence became evident by ultrastructural analyses. This early dysfunction was fully reversible if the exposure was terminated promptly. In cristae and utricles, the distinct junctions formed between type I HCs (HCI) and calyx endings were completely dismantled at these early stages of reversible dysfunction, and completely rebuilt during washout. Immunohistochemical observations revealed loss and recovery of the junction proteins caspr1 and tenascin-C; while RT-PCR indicated that their loss was not due to decreased gene expression. KCNQ4 was mislocalized during intoxication and recovered control-like localization after washout. At early stages of the intoxication, the calyces could be classified as showing intact or lost junctions, indicating that calyceal junction dismantlement is triggered on a calyx-by-calyx basis. Chronic toxicity also altered the presence of ribeye, PSD-95 and GluA2 puncta in the calyces. These synaptic alterations varied between the two types of calyx endings (formed by calyx-only or dimorphic afferents) and some persisted at the end of the washout period. The present data reveal new forms of plasticity of the calyx endings in adult mammals, including a robust capacity for rebuilding the calyceal junction. These findings contribute to a better understanding of the phenomena involved in progressive vestibular dysfunction and its potential recovery during and after ototoxic exposure.
Novel Insights and Therapeutics in Multiple Sclerosis
Authors: Wagner Catriona A. , Goverman Joan M.
Published: August 2015

The last twelve years have witnessed the development of new therapies for relapsing-remitting multiple sclerosis that demonstrate increased efficacy relative to previous therapies. Many of these new drugs target the inflammatory phase of disease by manipulating different aspects of the immune system. While these new treatments are promising, the development of therapies for patients with progressive multiple sclerosis remains a significant challenge. We discuss the distinct mechanisms that may contribute to these two types of multiple sclerosis and the implications of these differences in the development of new therapeutic targets for this debilitating disease.
Freshwater distributions and water mass structure in the Amundsen Sea Polynya region, Antarctica
Authors: Randall-Goodwin E. , Meredith M. P. , Jenkins A. , Yager P. L. , Sherrell R. M. , Abrahamsen E. P. , Guerrero R. , Yuan X. , Mortlock R. A. , Gavahan K. , Alderkamp A.-C. , Ducklow H. , Robertson R. , Stammerjohn S. E.
Published: August 2015

We present the first densely-sampled hydrographic survey of the Amundsen Sea Polynya (ASP) region, including a detailed characterization of its freshwater distributions. Multiple components contribute to the freshwater budget, including precipitation, sea ice melt, basal ice shelf melt, and iceberg melt, from local and non-local sources. We used stable oxygen isotope ratios in seawater (δ18O) to distinguish quantitatively the contributions from sea ice and meteoric-derived sources. Meteoric fractions were high throughout the winter mixed layer (WML), with maximum values of 2–3% (±0.5%). Because the ASP region is characterized by deep WMLs, column inventories of total meteoric water were also high, ranging from 10–13 m (±2 m) adjacent to the Dotson Ice Shelf (DIS) and in the deep trough to 7–9 m (±2 m) in shallower areas. These inventories are at least twice those reported for continental shelf waters near the western Antarctic Peninsula. Sea ice melt fractions were mostly negative, indicating net (annual) sea ice formation, consistent with this area being an active polynya. Independently determined fractions of subsurface glacial meltwater (as one component of the total meteoric inventory) had maximum values of 1–2% (±0.5%), with highest and shallowest maximum values at the DIS outflow (80–90 m) and in iceberg-stirred waters (150–200 m). In addition to these upwelling sites, contributions of subsurface glacial meltwater could be traced at depth along the ∼ 27.6 isopycnal, from which it mixes into the WML through various processes. Our results suggest a quasi-continuous supply of melt-laden iron-enriched seawater to the euphotic zone of the ASP and help to explain why the ASP is Antarctica’s most biologically productive polynya per unit area.
Improve Synergy Between Health Information Exchange and Electronic Health Records
to Increase Rates of Continuously Insured Patients
Authors: Gold Rachel , Burdick Tim , Angier Heather , Wallace Lorraine , Nelson Christine , Likumahuwa-Ackman Sonja , Sumic Aleksandra , DeVoe Jennifer E.
Published: August 2015

Introduction: The Affordable Care Act increases health insurance options, yet many
Americans may struggle to consistently maintain coverage. While health care providers
have traditionally not been involved in providing insurance enrollment support to their
patients, the ability for them to do so now exists. We propose that providers could
capitalize on the expansion of electronic health records (EHRs) and the advances in
health information exchanges (HIEs) to improve their patients’ insurance coverage rates
and continuity.Evidence for Argument: We describe a project in which we are building
strategies for linking and thus improving synergy between payer and EHR data. Through
this effort, care teams will have access to new automated tools and increased EHR
functionality designed to help them assist their patients in obtaining and maintaining
health insurance coverage.Suggestion for the Future: The convergence of increasing EHR
adoption, improving HIE functionality, and expansions in insurance coverage options,
creates new opportunities for clinics to help their patients obtain public health
insurance. Harnessing this nascent ability to exchange information between payers and
providers may improve synergies between HIE and EHRs, and thus support clinic-based
efforts to keep patients continuously insured.