bluuebunny/crossref_metadata_2025 huggingface dataset:
Linguistic Analysis of Clinical Communications
Authors: Rantanen Esa , Alm Cecilia Ovesdotter , Worrell Tracy , Valentage Nancy , Iuliucci Nick
Published: July 2014

This project took a unique perspective on the investigation of decision making in healthcare by examining clinician-patient consultation using methods from linguistics and communication. Our goal was to identify cognitive and behavioral patterns in interactions of clinicians-in-trainings with patients that correspond to decision making processes in time constrained situations. Objective measures of clinician-patient communications in both naturalistic and simulated settings is a promising way to examine clinician decision making under uncertainty and time pressure, and to identify specific errors in decision making that may lead to misdiagnoses. We sought to detect distinguishable patterns of communication adopted by clinicians-in-training in clinical consultation settings under time pressure. A pilot study reported in this paper provides objective measurement tools to study miscommunication within clinician-patient consultations and may positively influence the treatments and services offered within patient consultations.
Care Coordination Models Applied to Cancer Survivorship
Authors: Sun Wenjun , Kuehn Katherine A , Wiegmann Douglas A. , Tevaarwerk Amye , Sesto Mary E.
Published: July 2014

Fragmented and uncoordinated care following active cancer treatment is an important public health problem for many of the 13 million adult cancer survivors not receiving necessary or routine follow-up care. Patients may receive surgery, radiotherapy, or chemotherapy in different departments or health care organizations. The coordination among and between multiple care providers, survivors, and family members is of great importance to cancer survivors to ensure optimal care. While frameworks and models are widely used to guide coordination improvement efforts for chronic diseases, the diversity of these models makes it difficult to choose which model is the best fit for coordinating cancer survivors’ care. This paper analyzes common models used for coordinating chronic and complex disease care to identify key elements in the models that are essential for successfully applying a model to cancer survivors to improve their care coordination.
TO VAD OR NOT TO VAD
Authors: Friedman Emily , McMahon Molly
Published: July 2014

As part of its Healthy Aging & Independent Living (HAIL) initiative, Mayo Clinic Center for Innovation (CFI) examined the patient experience regarding the decision to receive a ventricular assistive device (VAD) implant, and patients’ quality of life after the surgery. As health care technology continues to develop, more people will be living longer, fuller lives with the assistance of wearable/implantable medical devices such as the VAD. This case study examined and made recommendations on ways for the Mayo Clinic VAD Committee to improve the program.
When human factors and design unite: using visual language and usability testing to improve instructions for a home-use medication infusion pump
Authors: Abts Natalie , Hernandez Angelica , Caplan Stanley , Hettinger A. Zachary , Larsen Ethan , Lewis Vicki R.
Published: July 2014

Use of medical devices in the home that had previously been used in a healthcare facility is increasing as more care is being transferred to the home environment. To accommodate these changes, instructions for use (IFU) for these devices must be clear and understandable for patients and caregivers to be able to operate them safety. IFUs that use illustrations and graphics rather than text to convey information may make user guides more accessible. This project consisted of two phases to determine the appropriate design of a visual user guide (VUG). During the first phase, a heuristic evaluation of the manufacturer’s IFU for an infusion pump was conducted. In the second phase, the heuristic evaluation results were used to inform the development of a VUG. Two rounds of iterative user testing were then conducted with a sample of target end users, with each round resulting in updates to the VUG. Findings demonstrated both major deficiencies in the usability of the manufacturer’s IFU, and improvements in helpfulness ratings and subjective participant feedback as the VUG was updated based on testing recommendations. The study demonstrates the value of visual guides for patients using medical devices and the use of discount usability techniques to identify major design issues.
Assessing Instrument Usage Patterns in Multiple Long Duration Colorectal Surgical Proceduresto Categorise Decisions Made by Surgeons and Elicit Specific Design Needs
Authors: White Eoin , McMahon Muireann , Walsh Michael , Coffey J. Calvin , O’Sullivan Leonard
Published: July 2014

The aims of this study are twofold: firstly to apply a method of categorizing surgical instrument use during long duration laparoscopic procedures, and secondly to validate this method by applying it to multiple instances of a single procedure. Case studies were performed on several separate high definition recordings of laparoscopic sigmoid colectomy procedures to assess the actions performed by the surgeon. The Observer XT V11.0(Noldus 2011) software package was used to study specific instrument usage, the actions associated with each instrument, idle behavior time and instrument changeover times. The Observer XT V11.0 software package was an effective method of categorizing the actions during the procedure. The data from the case studies indicated that for this specific right handed operator, the right hand led the procedure, using the most instruments and separate actions. The left hand provided support through actions such as grasping and maneuvering only. The most used instrument was the suction/irrigation instrument, followed by the grasping instruments. Key operations such as stapling/dissecting occupied the least amount of time. More time was spent maneuvering the internal anatomy than mobilizing the sigmoid colon or creating an anastomosis or stoma. Once the actions of each hand during each procedure were categorized, high level statistical analyses were applied to the data. It was necessary to perform these analyses to normalize the data as each part of the laparoscopic sigmoid colectomy procedure utilized different instruments for different durations. The future applications of this work lie in the innovation of new instruments or approaches to laparoscopic surgery. In these case studies, more time was spent navigating to the surgery site than performing the mobilization of the colon. There would appear to be a previously unmet clinical need to innovate new approaches to this type of surgery to shorten the duration of the surgery while preserving or improving the clinical outcome for the patient. More case studies are needed to confirm the validity of this claim.
Characterisation and corrosion performance of HVOF sprayed Ni–10 wt-%Ti coatings
Authors: Verdian M. M.
Published: July 2014

Mechanically alloyed Ni–10 wt-%Ti powders were deposited on 1045 steel substrate using high velocity oxy-fuel (HVOF) thermal spraying process. The microstructure and phase composition of coatings were evaluated by scanning electron microscopy (SEM) and X-ray diffraction (XRD) analysis. The results showed that the phase composition of feedstock powders was preserved during spraying and only supersaturated Ni(Ti) solid solution was present in the coatings. The hardness measurements showed that the hardness of coatings was about 510 HV (50 g). Tafel polarisation tests performed after 1 h immersion revealed that the corrosion behaviour of HVOF Ni–Ti coatings was not affected by substrate. However, delamination of air plasma sprayed (APS) Ni–10 wt-%Ti coatings and significant corrosion of substrate was observed in similar conditions. For HVOF Ni–Ti coating and after 24 h of immersion time, the corrosion of underlying substrate was observed after polarisation measurements but no delamination of coating occurred.
A critical role of autocrine sonic hedgehog signaling in human CD138+ myeloma cell survival and drug resistance
Authors: Liu Zhiqiang , Xu Jingda , He Jin , Zheng Yuhuan , Li Haiyan , Lu Yong , Qian Jianfei , Lin Pei , Weber Donna M. , Yang Jing , Yi Qing
Published: July 2014

Key Points

CD138+ MM cells are a major source of SHH. Autocrine SHH enhances MM drug resistance.
Platelet bioreactor-on-a-chip
Authors: Thon Jonathan N. , Mazutis Linas , Wu Stephen , Sylman Joanna L. , Ehrlicher Allen , Machlus Kellie R. , Feng Qiang , Lu Shijiang , Lanza Robert , Neeves Keith B. , Weitz David A. , Italiano Joseph E.
Published: July 2014

Key Points

We have developed a biomimetic microfluidic platelet bioreactor that recapitulates bone marrow and blood vessel microenvironments. Application of shear stress in this bioreactor triggers physiological proplatelet production, and platelet release.
Defining minimal residual disease in acute myeloid leukemia: which platforms are ready for “prime time”?
Authors: Grimwade David , Freeman Sylvie D.
Published: July 2014

The past 40 years have witnessed major advances in defining the cytogenetic aberrations, mutational landscape, epigenetic profiles, and expression changes underlying hematological malignancies. Although it has become apparent that acute myeloid leukemia (AML) is highly heterogeneous at the molecular level, the standard framework for risk stratification guiding transplant practice in this disease remains largely based on pretreatment assessment of cytogenetics and a limited panel of molecular genetic markers, coupled with morphological assessment of bone marrow (BM) blast percentage after induction. However, application of more objective methodology such as multiparameter flow cytometry (MFC) has highlighted the limitations of morphology for reliable determination of remission status. Moreover, there is a growing body of evidence that detection of subclinical levels of leukemia (ie, minimal residual disease, MRD) using MFC or molecular-based approaches provides powerful independent prognostic information. Consequently, there is increasing interest in the use of MRD detection to provide early end points in clinical trials and to inform patient management. However, implementation of MRD assessment into clinical practice remains a major challenge, hampered by differences in the assays and preferred analytical methods employed between routine laboratories. Although this should be addressed through adoption of standardized assays with external quality control, it is clear that the molecular heterogeneity of AML coupled with increasing understanding of its clonal architecture dictates that a “one size fits all” approach to MRD detection in this disease is not feasible. However, with the range of platforms now available, there is considerable scope to realistically track treatment response in every patient.
Approaches for the design of reduced toxicant emission cigarettes
Authors: Dittrich David J , Fieblekorn Richard T , Bevan Michael J , Rushforth David , Murphy James J , Ashley Madeleine , McAdam Kevin G , Liu Chuan , Proctor Christopher J
Published: July 2014

Cigarette smoking causes serious diseases through frequent and prolonged exposure to toxicants. Technologies are being developed to reduce smokers’ toxicant exposure, including filter adsorbents, tobacco treatments and substitutes. This study examined the effect of modifications to filter ventilation, variations in cigarette circumference and active charcoal filter length and loading, as well as combinations of these features in a reduced-toxicant prototype (RTP) cigarette, on the yields of toxicants in cigarette smoke. An air-dilution mechanism, called split-tipping, was developed in which a band of porous paper in the centre of the filter tipping functions to minimise the loss of effective filter ventilation that occurs at the high flow rates encountered during human-smoking, and to facilitate the diffusional loss of volatile toxicants. As compared with conventional filter ventilation cigarettes, split-tipping reduced tar and volatile smoke constituent emissions under high flow rate machine-smoking conditions, most notably for products with a 1-mg ISO tar yield. Furthermore, mouth level exposure (MLE) to tar and nicotine was reduced among smokers of 1-mg ISO tar cigarettes in comparison to smokers of cigarettes with traditional filter ventilation. For higher ISO tar level cigarettes, however, there were no significant reductions in MLE. Smaller cigarette circumferences reduced sidestream toxicant yields and modified the balance of mainstream smoke chemistry with reduced levels of aromatic amines and benzo[a]pyrene but increased yields of formaldehyde. Smaller circumference cigarettes also had lower mainstream yields of volatile toxicants. Longer cigarette filters containing increased levels of high-activity carbon (HAC) showed reduced machine-smoking yields of volatile toxicants: with up to 97% removal for some volatile toxicants at higher HAC loadings. Split-tipping was combined with optimal filter length and cigarette circumference in an RTP cigarette that gave significantly lower mainstream (up to ~90%) and sidestream (predominately 20%–60%) smoke yields of numerous toxicants as compared with a commercial comparator cigarette under machine-smoking conditions. Significantly lower mainstream and sidestream smoke toxicant yields were observed for an RTP cigarette comprising several toxicant reducing technologies; these observations warrant further evaluation in clinical studies where real-world relevance can be tested using biomarkers of exposure and physiological effect.
Short term treatment versus long term management of neck and back disability in older adults utilizing spinal manipulative therapy and supervised exercise: a parallel-group randomized clinical trial evaluating relative effectiveness and harms
Authors: Vihstadt Corrie , Maiers Michele , Westrom Kristine , Bronfort Gert , Evans Roni , Hartvigsen Jan , Schulz Craig
Published: July 2014

Background

Back and neck disability are frequent in older adults resulting in loss of function and independence. Exercise therapy and manual therapy, like spinal manipulative therapy (SMT), have evidence of short and intermediate term effectiveness for spinal disability in the general population and growing evidence in older adults. For older populations experiencing chronic spinal conditions, long term management may be more appropriate to maintain improvement and minimize the impact of future exacerbations. Research is limited comparing short courses of treatment to long term management of spinal disability.

The primary aim is to compare the relative effectiveness of 12 weeks versus 36 weeks of SMT and supervised rehabilitative exercise (SRE) in older adults with back and neck disability.

Methods/Design

Randomized, mixed-methods, comparative effectiveness trial conducted at a university-affiliated research clinic in the Minneapolis/St. Paul, Minnesota metropolitan area.

Participants

Independently ambulatory community dwelling adults ≥ 65 years of age with back and neck disability of minimum 12 weeks duration (n = 200).

Interventions

12 weeks SMT + SRE or 36 weeks SMT + SRE.

Randomization

Blocked 1:1 allocation; computer generated scheme, concealed in sequentially numbered, opaque, sealed envelopes.

Blinding

Functional outcome examiners are blinded to treatment allocation; physical nature of the treatments prevents blinding of participants and providers to treatment assignment.

Primary endpoint

36 weeks post-randomization.

Data collection

Self-report questionnaires administered at 2 baseline visits and 4, 12, 24, 36, 52, and 78 weeks post-randomization. Primary outcomes include back and neck disability, measured by the Oswestry Disability Index and Neck Disability Index. Secondary outcomes include pain, general health status, improvement, self-efficacy, kinesiophobia, satisfaction, and medication use. Functional outcome assessment occurs at baseline and week 37 for hand grip strength, short physical performance battery, and accelerometry. Individual qualitative interviews are conducted when treatment ends. Data on expectations, falls, side effects, and adverse events are systematically collected.

Primary analysis

Linear mixed-model method for repeated measures to test for between-group differences with baseline values as covariates.

Discussion

Treatments that address the management of spinal disability in older adults may have far reaching implications for patient outcomes, clinical guidelines, and healthcare policy.

Trial registry

www.ClinicalTrials.gov; Identifier: NCT01057706.
A study protocol for the profile of pain in older women: assessing the multi dimensional nature of the experience of pain in arthritis
Authors: de Luca Katie , Parkinson Lynne , Byles Julie
Published: July 2014

Background

Arthritis is a significant contributor to illness, pain and disability and imposes a considerable burden upon the community. Pain is a cardinal symptom of arthritis and has significant implications on biopsychosocial wellbeing. The multidimensional nature of the experience of pain in arthritis has not been well defined in community-based samples.

Aims

The two aims of this study are to generate profiles of pain from a community sample of older women and to compare profiles for women with and without arthritis.

Methods

The sub study is a cross-sectional postal survey of 700 Australian community-based women. The survey includes a range of measures on health, arthritis and pain that will be used to examine the multidimensional nature of the experience of pain in arthritis and generate profiles of pain.

Discussion

With no core set of measures for the evaluation of arthritis pain, this survey was created from an amalgamation of measures to capture multiple dimensions of pain. Findings from this study will assist in defining the symptom of pain in arthritis and may lead to further research in evidence-based treatment options for people with arthritis.
Corset: enabling differential gene expression analysis for de novoassembled transcriptomes
Authors: Davidson Nadia M , Oshlack Alicia
Published: July 2014

Next generation sequencing has made it possible to perform differential gene expression studies in non-model organisms. For these studies, the need for a reference genome is circumvented by performing de novo assembly on the RNA-seq data. However, transcriptome assembly produces a multitude of contigs, which must be clustered into genes prior to differential gene expression detection. Here we present Corset, a method that hierarchically clusters contigs using shared reads and expression, then summarizes read counts to clusters, ready for statistical testing. Using a range of metrics, we demonstrate that Corset out-performs alternative methods. Corset is available from https://code.google.com/p/corset-project/.
Molecularly and clinically related drugs and diseases are enriched in phenotypically similar drug-disease pairs
Authors: Vogt Ingo , Prinz Jeanette , Campillos Mónica
Published: July 2014

Background

The incomplete understanding of disease causes and drug mechanisms of action often leads to ineffective drug therapies or side effects. Therefore, new approaches are needed to improve treatment decisions and to elucidate molecular mechanisms underlying pathologies and unwanted drug effects.

Methods

We present here the first analysis of phenotypically related drug-disease pairs. The phenotypic similarity between 4,869 human diseases and 1,667 drugs was evaluated using an ontology-based semantic similarity approach to compare disease symptoms with drug side effects. We assessed and visualized the enrichment over random of clinical and molecular relationships among drug-disease pairs that share phenotypes using lift plots. To determine the associations between drug and disease classes enriched among phenotypically related pairs we employed a network-based approach combined with Fisher's exact test.

Results

We observed that molecularly and clinically related (for example, indication or contraindication) drugs and diseases are likely to share phenotypes. An analysis of the relations between drug mechanisms of action (MoAs) and disease classes among highly similar pairs revealed known and suspected MoA-disease relationships. Interestingly, we found that contraindications associated with high phenotypic similarity often involve diseases that have been reported as side effects of the drug, probably due to common mechanisms. Based on this, we propose a list of 752 precautions or potential contraindications for 486 drugs.

Conclusions

Phenotypic similarity between drugs and diseases facilitates the proposal of contraindications and the mechanistic understanding of diseases and drug side effects.
Parathyroid Hormone-Related Protein: Potential Therapeutic Target for Melanoma Invasion and Metastasis
Authors: Huang Dao Chao , Yang Xian Fang , Ochietti Benoît , Fadhil Ibtihal , Camirand Anne , Kremer Richard
Published: July 2014

The role of PTHrP in the highly metastatic human melanoma disease is not known. This study investigates the mechanisms of action of this secreted factor through homozygous inactivation of the Pthrp gene in A375 human melanoma cells. In vitro, Pthrp-ablated cells (knockout [KO]-A375, −/−) showed decreased motility and anchorage-independent growth, rounder morphology, and a significant reduction in invasion capacity compared with nonablated A375 cells (wild-type [WT]-A375, +/+). PTHrP peptide 1–34 and conditioned medium from WT-A375 cells partially restored the invasive phenotype in KO-A375. Pthrp ablation substantially decreased actin polymerization, matrix metallopeptidase 9 expression and focal adhesion kinase phosphorylation. In vivo, green fluorescent protein-transduced ablated and nonablated A375 cells were injected intracardially or sc into nude mice to study proliferation and multiorgan metastasis. Dissemination of injected Pthrp-ablated cells to lung and liver was reduced by 85% and 50%, respectively, compared with nonablated controls (120 hours after injection). The number of metastatic lesions and the percentage of animals with metastasis were markedly lower in mice injected with Pthrp-ablated A375, and 45% of these animals survived a 7-week period compared with 15% of mice injected with nonablated WT-A375. When mice injected with WT-A375 were treated with our blocking anti-PTHrP monoclonal antibody raised against the first 33 amino acids of human PTHrP, tumor size was decreased by more than 80% over 4 weeks and survival was significantly improved over 8 months. This study provides direct evidence of the major role for PTHrP in melanoma invasion and metastasis and suggests that agents that suppress PTHrP may be beneficial against melanoma progression.
Estrogen Receptor (ER) Agonists Differentially Regulate Neuroangiogenesis in Peritoneal Endometriosis via the Repellent Factor SLIT3
Authors: Greaves Erin , Collins Frances , Esnal-Zufiaurre Arantza , Giakoumelou Sevasti , Horne Andrew W. , Saunders Philippa T. K.
Published: July 2014

Endometriosis is an estrogen-dependent neurovascular disorder characterized by growth of endometrial tissue (lesions) outside the uterine cavity. Patients suffer chronic pelvic pain, and it has been proposed that co-recruitment of nerves/blood vessels (neuroangiogenesis) into the lesions is fundamental to the development of painful symptoms. We hypothesized that estrogen-dependent regulation of axonal guidance molecules of the SLIT/ROBO (Roundabout) family could play a role in neuroangiogenesis occurring in endometriosis lesions found on the peritoneal wall. In tissue samples from human patients and a mouse model of endometriosis, concentrations of mRNA encoded by SLIT3 were significantly higher in lesions than normal peritoneum. Estrogen regulation of SLIT3 was investigated using 17β-estradiol and selective agonists for each subtype of estrogen receptor (ER) (ERα agonist, 4,4′,4″-(4-propyl-(1H)-pyrazole-1,3,5-tryl) trisphenol; ERβ agonist, 2,3-bis(4-hydroxy-phenyl)-propionitrile [DPN]). In mice, DPN (EC50 0.85) increased Slit3 mRNA concentrations compared with hormone-depleted and 17β-estradiol-treated (EC50 0.1) animals and decreased the density of nerves but not vessels in endometriosis lesions. SLIT3 mRNA concentrations were increased in DPN-treated human endometrial endothelial cells and in 4,4′,4″-(4-propyl-(1H)-pyrazole-1,3,5-tryl) trisphenol-treated (EC50 200) rat dorsal root ganglia neurons. Functional assays (neurite outgrowth, network formation) revealed that SLIT3 promotes angiogenesis but decreases neurogenesis. In conclusion, these data suggest that estrogen-dependent expression of SLIT3 may play a key role in regulating nerve-vessel interactions within the complex microenvironment of endometriosis lesions.
5-HT Obesity Medication Efficacy via POMC Activation is Maintained During Aging
Authors: Burke Luke K. , Doslikova Barbora , D'Agostino Giuseppe , Garfield Alastair S. , Farooq Gala , Burdakov Denis , Low Malcolm J. , Rubinstein Marcelo , Evans Mark L. , Billups Brian , Heisler Lora K.
Published: July 2014

The phenomenon commonly described as the middle-age spread is the result of elevated adiposity accumulation throughout adulthood until late middle-age. It is a clinical imperative to gain a greater understanding of the underpinnings of age-dependent obesity and, in turn, how these mechanisms may impact the efficacy of obesity treatments. In particular, both obesity and aging are associated with rewiring of a principal brain pathway modulating energy homeostasis, promoting reduced activity of satiety pro-opiomelanocortin (POMC) neurons within the arcuate nucleus of the hypothalamus (ARC). Using a selective ARC-deficient POMC mouse line, here we report that former obesity medications augmenting endogenous 5-hydroxytryptamine (5-HT) activity d-fenfluramine and sibutramine require ARC POMC neurons to elicit therapeutic appetite-suppressive effects. We next investigated whether age-related diminished ARC POMC activity therefore impacts the potency of 5-HT obesity pharmacotherapies, lorcaserin, d-fenfluramine, and sibutramine and report that all compounds reduced food intake to a comparable extent in both chow-fed young lean (3–5 months old) and middle-aged obese (12–14 months old) male and female mice. We provide a mechanism through which 5-HT anorectic potency is maintained with age, via preserved 5-HT–POMC appetitive anatomical machinery. Specifically, the abundance and signaling of the primary 5-HT receptor influencing appetite via POMC activation, the 5-HT2CR, is not perturbed with age. These data reveal that although 5-HT obesity medications require ARC POMC neurons to achieve appetitive effects, the anorectic efficacy is maintained with aging, findings of clinical significance to the global aging obese population.
A Novel Model for Neuroendocrine Toxicology: Neurobehavioral Effects of BPA Exposure in a Prosocial Species, the Prairie Vole (Microtus ochrogaster)
Authors: Sullivan Alana W. , Beach Elsworth C. , Stetzik Lucas A. , Perry Amy , D'Addezio Alyssa S. , Cushing Bruce S. , Patisaul Heather B.
Published: July 2014

Impacts on brain and behavior have been reported in laboratory rodents after developmental exposure to bisphenol A (BPA), raising concerns about possible human effects. Epidemiological data suggest links between prenatal BPA exposure and altered affective behaviors in children, but potential mechanisms are unclear. Disruption of mesolimbic oxytocin (OT)/vasopressin (AVP) pathways have been proposed, but supporting evidence is minimal. To address these data gaps, we employed a novel animal model for neuroendocrine toxicology: the prairie vole (Microtus ochrogaster), which are more prosocial than lab rats or mice. Male and female prairie vole pups were orally exposed to 5-μg/kg body weight (bw)/d, 50-μg/kg bw/d, or 50-mg/kg bw/d BPA or vehicle over postnatal days 8–14. Subjects were tested as juveniles in open field and novel social tests and for partner preference as adults. Brains were then collected and assessed for immunoreactive (ir) tyrosine hydroxylase (TH) (a dopamine marker) neurons in the principal bed nucleus of the stria terminalis (pBNST) and TH-ir, OT-ir, and AVP-ir neurons in the paraventricular nucleus of the hypothalamus (PVN). Female open field activity indicated hyperactivity at the lowest dose and anxiety at the highest dose. Effects on social interactions were also observed, and partner preference formation was mildly inhibited at all dose levels. BPA masculinized principal bed nucleus of the stria terminalis TH-ir neuron numbers in females. Additionally, 50-mg/kg bw BPA-exposed females had more AVP-ir neurons in the anterior PVN and fewer OT-ir neurons in the posterior PVN. At the 2 lowest doses, BPA eliminated sex differences in PVN TH-ir neuron numbers and reversed this sex difference at the highest dose. Minimal behavioral effects were observed in BPA-exposed males. These data support the hypothesis that BPA alters affective behaviors, potentially via disruption of OT/AVP pathways.
Maternal Diet-induced Obesity Programs Cardiovascular Dysfunction in Adult Male Mouse Offspring Independent of Current Body Weight
Authors: Blackmore Heather L. , Niu Youguo , Fernandez-Twinn Denise S. , Tarry-Adkins Jane L. , Giussani Dino A. , Ozanne Susan E.
Published: July 2014

Obese pregnancies are not only associated with adverse consequences for the mother but also the long-term health of her child. Human studies have shown that individuals from obese mothers are at increased risk of premature death from cardiovascular disease (CVD), but are unable to define causality. This study aimed to determine causality using a mouse model of maternal diet–induced obesity. Obesity was induced in female C57BL/6 mice by feeding a diet rich in simple sugars and saturated fat 6 weeks prior to pregnancy and throughout pregnancy and lactation. Control females were fed laboratory chow. Male offspring from both groups were weaned onto chow and studied at 3, 5, 8, and 12 weeks of age for gross cardiac morphometry using stereology, cardiomyocyte cell area by histology, and cardiac fetal gene expression using qRT-PCR. Cardiac function was assessed by isolated Langendorff technology at 12 weeks of age and hearts were analyzed at the protein level for the expression of the β1 adrenergic receptor, muscarinic type-2 acetylcholine receptor, and proteins involved in cardiac contraction. Offspring from obese mothers develop pathologic cardiac hypertrophy associated with re-expression of cardiac fetal genes. By young adulthood these offspring developed severe systolic and diastolic dysfunction and cardiac sympathetic dominance. Importantly, cardiac dysfunction occurred in the absence of any change in corresponding body weight and despite the offspring eating a healthy low-fat diet. These findings provide a causal link to explain human observations relating maternal obesity with premature death from CVD in her offspring.
Inhibin at 90: From Discovery to Clinical Application, a Historical Review
Authors: Makanji Yogeshwar , Zhu Jie , Mishra Rama , Holmquist Chris , Wong Winifred P. S. , Schwartz Neena B. , Mayo Kelly E. , Woodruff Teresa K.
Published: July 2014

When it was initially discovered in 1923, inhibin was characterized as a hypophysiotropic hormone that acts on pituitary cells to regulate pituitary hormone secretion. Ninety years later, what we know about inhibin stretches far beyond its well-established capacity to inhibit activin signaling and suppress pituitary FSH production. Inhibin is one of the major reproductive hormones involved in the regulation of folliculogenesis and steroidogenesis. Although the physiological role of inhibin as an activin antagonist in other organ systems is not as well defined as it is in the pituitary-gonadal axis, inhibin also modulates biological processes in other organs through paracrine, autocrine, and/or endocrine mechanisms. Inhibin and components of its signaling pathway are expressed in many organs. Diagnostically, inhibin is used for prenatal screening of Down syndrome as part of the quadruple test and as a biochemical marker in the assessment of ovarian reserve. In this review, we provide a comprehensive summary of our current understanding of the biological role of inhibin, its relationship with activin, its signaling mechanisms, and its potential value as a diagnostic marker for reproductive function and pregnancy-associated conditions.
Long-term Efficacy of Ultrasound-Guided Laser Ablation for Benign Solid Thyroid Nodules. Results of a Three-Year Multicenter Prospective Randomized Trial
Authors: Papini E. , Rago T. , Gambelunghe G. , Valcavi R. , Bizzarri G. , Vitti P. , De Feo P. , Riganti F. , Misischi I. , Di Stasio E. , Pacella C. M.
Published: July 2014

Background:

The aim of the present trial on ultrasound (US)-guided laser ablation therapy (LAT) of solid thyroid nodules is to assess long-term clinical efficacy, side effects, and predictability of outcomes in different centers operating with the same procedure.

Patients:

Two hundred consecutive patients were randomly assigned to a single LAT session (group 1, 101 cases) or to follow-up (group 2, 99 cases) at four thyroid referral centers. Entry criteria were: solid thyroid nodule with volume of 6–17 mL, repeat benign cytological findings, normal thyroid function, no autoimmunity, and no thyroid gland treatment.

Methods:

Group 1: LAT was performed in a single session with two optical fibers, a 1064 nm Nd-YAG laser source, and an output power of 3 W. Volume and local symptom changes were evaluated 1, 6, 12, 24, and 36 months after LAT. Side effects and tolerability of treatment were registered. Group 2: Follow-up with no treatment.

Results:

One patient was lost to follow-up in each group. Group 1: Volume decrease after LAT was −49 ± 22%, −59 ± 22%, −60 ± 24%, and −57 ± 25% at 6, 12, 24, and 36 months, respectively (P < .001 vs baseline). LAT resulted in a nodule reduction of >50% in 67.3% of cases (P < .001). Local symptoms decreased from 38 to 8% of cases (P = .002) and cosmetic signs from 72 to 16% of cases (P = .001). Baseline size, presence of goiter (P = .55), or US findings (fluid component ≤ 20% [P = .84], halo [P = .46], vascularization [P = .98], and calcifications [P = .06]) were not predictive factors of a volume decrease > 50%. The procedure was well tolerated in most (92%) cases. No changes in thyroid function or autoimmunity were observed. In group 2, nodule volume increased at 36 months (25 ± 42%; P = .04). The efficacy and tolerability of the procedure were similar in different centers.

Conclusions:

A single LAT treatment of solid nodules results in significant and persistent volume reduction and local symptom improvement, in the absence of thyroid function changes.
On operator-valued monotone independence
Authors: Hasebe Takahiro , Saigo Hayato
Published: July 2014

We investigate operator-valued monotone independence, a noncommutative version of independence for conditional expectation. First we introduce operator-valued monotone cumulants to clarify the whole theory and show the moment-cumulant formula. As an application, one can obtain an easy proof of the central limit theorem for the operator-valued case. Moreover, we prove a generalization of Muraki’s formula for the sum of independent random variables and a relation between generating functions of moments and cumulants.
The dynamics of plant plasma membrane proteins: PINs and beyond
Authors: Luschnig Christian , Vert Grégory
Published: July 2014

Plants are permanently situated in a fixed location and thus are well adapted to sense and respond to environmental stimuli and developmental cues. At the cellular level, several of these responses require delicate adjustments that affect the activity and steady-state levels of plasma membrane proteins. These adjustments involve both vesicular transport to the plasma membrane and protein internalization via endocytic sorting. A substantial part of our current knowledge of plant plasma membrane protein sorting is based on studies of PIN-FORMED (PIN) auxin transport proteins, which are found at distinct plasma membrane domains and have been implicated in directional efflux of the plant hormone auxin. Here, we discuss the mechanisms involved in establishing such polar protein distributions, focusing on PINs and other key plant plasma membrane proteins, and we highlight the pathways that allow for dynamic adjustments in protein distribution and turnover, which together constitute a versatile framework that underlies the remarkable capabilities of plants to adjust growth and development in their ever-changing environment.
The cellular and molecular etiology of the craniofacial defects in the avian ciliopathic mutant talpid2
Authors: Chang Ching-Fang , Schock Elizabeth N. , O'Hare Elizabeth A. , Dodgson Jerry , Cheng Hans H. , Muir William M. , Edelmann Richard E. , Delany Mary E. , Brugmann Samantha A.
Published: July 2014

talpid2 is an avian autosomal recessive mutant with a myriad of congenital malformations, including polydactyly and facial clefting. Although phenotypically similar to talpid3, talpid2 has a distinct facial phenotype and an unknown cellular, molecular and genetic basis. We set out to determine the etiology of the craniofacial phenotype of this mutant. We confirmed that primary cilia were disrupted in talpid2 mutants. Molecularly, we found disruptions in Hedgehog signaling. Post-translational processing of GLI2 and GLI3 was aberrant in the developing facial prominences. Although both GLI2 and GLI3 processing were disrupted in talpid2 mutants, only GLI3 activator levels were significantly altered in the nucleus. Through additional fine mapping and whole-genome sequencing, we determined that the talpid2 phenotype was linked to a 1.4 Mb region on GGA1q that contained the gene encoding the ciliary protein C2CD3. We cloned the avian ortholog of C2CD3 and found its expression was ubiquitous, but most robust in the developing limbs and facial prominences. Furthermore, we found that C2CD3 is localized proximal to the ciliary axoneme and is important for docking the mother centriole to the ciliary vesicle and cell membrane. Finally, we identified a 19 bp deletion in talpid2 C2CD3 that produces a premature stop codon, and thus a truncated protein, as the likely causal allele for the phenotype. Together, these data provide insight into the cellular, molecular and genetic etiology of the talpid2 phenotype. Our data suggest that, although the talpid2 and talpid3 mutations affect a common ciliogenesis pathway, they are caused by mutations in different ciliary proteins that result in differences in craniofacial phenotype.
Retinoic acid controls body axis extension by directly repressing Fgf8 transcription
Authors: Kumar Sandeep , Duester Gregg
Published: July 2014

Retinoic acid (RA) generated in the mesoderm of vertebrate embryos controls body axis extension by downregulating Fgf8 expression in cells exiting the caudal progenitor zone. RA activates transcription by binding to nuclear RA receptors (RARs) at RA response elements (RAREs), but it is unknown whether RA can directly repress transcription. Here, we analyzed a conserved RARE upstream of Fgf8 that binds RAR isoforms in mouse embryos. Transgenic embryos carrying Fgf8 fused to lacZ exhibited expression similar to caudal Fgf8, but deletion of the RARE resulted in ectopic trunk expression extending into somites and neuroectoderm. Epigenetic analysis using chromatin immunoprecipitation of trunk tissues from E8.25 wild-type and Raldh2−/− embryos lacking RA synthesis revealed RA-dependent recruitment of the repressive histone marker H3K27me3 and polycomb repressive complex 2 (PRC2) near the Fgf8 RARE. The co-regulator RERE, the loss of which results in ectopic Fgf8 expression and somite defects, was recruited near the RARb RARE by RA, but was released from the Fgf8 RARE by RA. Our findings demonstrate that RA directly represses Fgf8 through a RARE-mediated mechanism that promotes repressive chromatin, thus providing valuable insight into the mechanism of RA-FGF antagonism during progenitor cell differentiation.
Facile and Green Decomposition of Dioxane with Catalytic Supercritical Water Gasification
Authors: Hara Takahiro , Nguyen Hung Thanh , Komiyama Masaharu
Published: July 2014

1,4-Dioxane, a persistent organic pollutant, was easily decomposed to methane and CO2 under supercritical water gasification (SCWG) conditions (400 °C, 26 MPa) in the presence of a Ni or Ru catalyst. Charcoal-supported Ru catalyst achieved 100% decomposition of 0.01 M dioxane at 450 °C within 90 min. This catalyst was able to clear the current wastewater discharge limit of 0.5 mg L−1 set by the Japanese Ministry of the Environment within 60 min reaction time at 400 °C for the same dioxane concentration and maintained its activity up to nine times of repeated usage. It is emphasized that the present process employs no chemical oxidants such as ozone or hydrogen peroxide.
Case Report: Group B Streptococcus meningitis in an adolescent
Authors: Vittorino Roselle , Hui-Yuen Joyce , Ratner Adam J. , Starr Amy , McCann Teresa
Published: July 2014

Streptococcus agalactiae (group B Streptococcus, GBS) usually colonizes the gastrointestinal and lower genital tracts of asymptomatic hosts, yet the incidence of invasive disease is on the rise. We describe a case of an 18 year old woman, recently diagnosed with lupus, who reported a spontaneous abortion six weeks prior to her hospitalization.  She presented with fever, altered mental status, and meningeal signs, paired with a positive blood culture for GBS. Magnetic resonance imaging of her brain demonstrated an extra-axial fluid collection, and she was diagnosed with meningitis.  She received prolonged intravenous antibiotic therapy and aggressive treatment for lupus, leading to clinical recovery. This case illustrates the importance of recognizing GBS as a potential pathogen in all patients presenting with CNS infection.
Case Report: Pneumocephalus after labor epidural anesthesia
Authors: Nistal-Nuño Beatriz , Gómez-Ríos Manuel Ángel
Published: July 2014

Lumbar epidural anesthesia is commonly used for labor analgesia. The 'loss-of- resistance' to air technique (LORA) is generally employed for recognition of the epidural space. One of the rare complications of this technique is pneumocephalus (PC). Here we describe the case of a parturient who developed a frontal headache when locating the epidural space using LORA. On the second day after epidural injection, the patient exhibited occipital headaches with gradual worsening. Computed tomography scans of the brain indicated PC. Following symptomatic treatment, our patient was discharged on the 13th day. We concluded that the amount of air used to identify the epidural space in LORA should be minimized, LORA should not be used after dural puncture and the use of saline avoids PC complications.
Cancer, strokes, menopause
Authors: Greener Mark
Published: July 2014

JOURNALS WATCH

In-depth analysis of the latest research. Compiled by Mark Greener
Introduction to nutrition in paediatric chronic kidney disease
Authors: Kearns Victoria , Brennan Eileen
Published: July 2014

Good nutrition is an important factor in the management of chronic kidney disease in paediatric patients, aiding growth and development. The recommendations for adequate nutritional intake depend on a number of factors and should be individual to each patient. In this article, Victoria Kearns and Eileen Brennan outline the nutrients needed.
Effect of manure and NPK to increase soil bacterial population of Azotobacter and Azospirillus in chili (Capsicum annum) cultivation
Authors: MUJIYATI MUJIYATI , SUPRIYADI SUPRIYADI
Published: July 2014

Mujiyati, Supriyadi. 2009. Effect of manure and NPK to increase soil bacterial population of Azotobacter and AzospirillumÂ in chili (Capsicum annum) cultivation. Nusantara Bioscience 1: 59-64. The objectives of this research were to find out the increaseÂ number of two bacterials populations, Azotobacter and Azospirillum, due to the use of manure fertilizer. The exsperiment was conductedÂ using group randomly designed with two treatments. The plant populations were treated (i) whithout fertilizer as the control, (ii) withÂ manure fertilizer, and (iii) with NPK fertilizer. Data was experimentally collected by planting chili in several plots treated by manure,Â with three replications. The field experiment was conducted in Gathak Village, Karangnongko Sub-district, Klaten District, CentralÂ Java. The data collected consist of the total population of Azotobacter and Azospirillum, nitrogen content in soil and the chili yield. TheÂ primary data of research were analyzed using ANOVA test and followed by LSD test, with the degree of significance by 95% .TheÂ results showed that the manure fertilizer can increase the population of bacteria as many as 0.02% (Azotobacter) and 0.46%Â (Azospirillum) when they were compared to the control one. So that it can increase the soil fertility when they were used in long time.Â Therefore increasing the nutrient availability in the soil was occurred. Application of manure fertilizer could increase the total nitrogenÂ content in the soil and it is very useful for the fertilizing of plants.
Characterization of white grub (Melolonthidae; Coleoptera) in salak plantation based on morphology and protein banding pattern
Authors: MARYATI KRISNANDARI TITIK , SUGIYARTO SUGIYARTO
Published: July 2014

Abstract. Maryati KT, Sugiyarto. 2010. Characterization of white grub (Melolonthidae; Coleoptera) in salak plantation based on morphology and protein banding pattern. Nusantara Bioscience 1: 72-77. This research aims to find out the white grub (Melolonthidae; Coleoptera) variability based on the morphological characteristic and protein banding pattern found in "salak pondoh" farm in Regencies of Sleman, Yogyakarta and Magelang, Central Java. Each area has five sampling points. Morphological analysis on white grub was conducted using descriptive method and analysis on protein banding pattern was conducted using qualitative analysis based on the presence or absence of band pattern on the gel, and qualitatively based on the relative mobility value (Rf) of protein. The result indicated that the white grub in Sleman and Magelang, based on morphology characteristic is only one species, namely Holothricia sp. Based on the protein banding pattern, the white grub sample has differences in protein band number and molecular protein weight.