bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic Adenosine Triphosphate Impairs Neutrophil Chemotaxis and Host Defense in Sepsis
Authors: Li Xiaoou , Kondo Yutaka , Bao Yi , Staudenmaier Laura , Lee Albert , Zhang Jingping , Ledderose Carola , Junger Wolfgang G.
Published: August 2016

Objective:

Sepsis remains an unresolved clinical problem. Therapeutic strategies focusing on inhibition of neutrophils (polymorphonuclear neutrophils) have failed, which indicates that a more detailed understanding of the underlying pathophysiology of sepsis is required. Polymorphonuclear neutrophil activation and chemotaxis require cellular adenosine triphosphate release via pannexin-1 channels that fuel autocrine feedback via purinergic receptors. In the current study, we examined the roles of endogenous and systemic adenosine triphosphate on polymorphonuclear neutrophil activation and host defense in sepsis.

Design:

Prospective randomized animal investigation and in vitro studies.

Setting:

Preclinical academic research laboratory.

Subjects:

Wild-type C57BL/6 mice, pannexin-1 knockout mice, and healthy human subjects used to obtain polymorphonuclear neutrophils for in vitro studies.

Interventions:

Wild-type and pannexin-1 knockout mice were treated with suramin or apyrase to block the endogenous or systemic effects of adenosine triphosphate. Mice were subjected to cecal ligation and puncture and polymorphonuclear neutrophil activation (CD11b integrin expression), organ (liver) injury (plasma aspartate aminotransferase), bacterial spread, and survival were monitored. Human polymorphonuclear neutrophils were used to study the effect of systemic adenosine triphosphate and apyrase on chemotaxis.

Measurements and Main Results:

Inhibiting endogenous adenosine triphosphate reduced polymorphonuclear neutrophil activation and organ injury, but increased the spread of bacteria and mortality in sepsis. By contrast, removal of systemic adenosine triphosphate improved bacterial clearance and survival in sepsis by improving polymorphonuclear neutrophil chemotaxis.

Conclusions:

Systemic adenosine triphosphate impairs polymorphonuclear neutrophil functions by disrupting the endogenous purinergic signaling mechanisms that regulate cell activation and chemotaxis. Removal of systemic adenosine triphosphate improves polymorphonuclear neutrophil function and host defenses, making this a promising new treatment strategy for sepsis.
Racial/Ethnic Differences in the Prevalence of Anxiety Using the Vanderbilt ADHD Scale in a Diverse Community Outpatient Setting
Authors: Bauer Nerissa S. , Yoder Rachel , Carroll Aaron E. , Downs Stephen M.
Published: August 2016

Objective:

Pediatric anxiety is prevalent but frequently underdiagnosed compared with other behavioral conditions in primary care practice. Pediatricians routinely screen for attention-deficit hyperactivity disorder using the Vanderbilt Rating Scale, which includes a short screen for anxiety. We sought to examine the prevalence of potential anxiety among patients whose parents originally had concerns of disruptive behavior in a diverse setting and examine differences in anxiety across ethnic groups using the Vanderbilt ADHD Diagnostic Rating Scale (VADRS).

Method:

This was a cross-sectional analysis of medical records data of children between the ages of 5 to 12 years whose parents had concerns of disruptive behavior and received primary care from May 25, 2010, to January 31, 2014 at 2 pediatric community health clinics in Indianapolis.

Results:

Sixteen percent of children whose parents had concerns for disruptive behavior screened positive for anxiety based on the VADRS screen. Hispanic parents were less likely to report symptoms of anxiety (Spanish speaking: adjusted odds ratio (AOR) 0.4, 95% confidence interval (CI), 0.2–0.8; English speaking: AOR 0.3, 95% CI, 0.1–0.9) compared with white and black families.

Conclusion:

Anxiety is detected at a lower rate among Hispanic pediatric patients using the VADRS. This may suggest differences in the performance of the VADRS among Spanish-speaking families.
Prenatal Drug Exposure and Adolescent Cortisol Reactivity: Association with Behavioral Concerns
Authors: Buckingham-Howes Stacy , Mazza Dayna , Wang Yan , Granger Douglas A. , Black Maureen M.
Published: August 2016

Objective:

To examine stress reactivity in a sample of adolescents with prenatal drug exposure (PDE) by examining the consequences of PDE on stress-related adrenocortical reactivity, behavioral problems, and drug experimentation during adolescence.

Methods:

Participants (76 PDE, 61 non-drug exposed [NE]; 99% African-American; 50% male; mean age = 14.17 yr, SD = 1.17) provided a urine sample, completed a drug use questionnaire, and provided saliva samples (later assayed for cortisol) before and after a mild laboratory stress task. Caregivers completed the Behavior Assessment System for Children, Second Edition (BASC II) and reported their relationship to the adolescent.

Results:

The NE group was more likely to exhibit task-related cortisol reactivity compared to the PDE group. Overall behavior problems and drug experimentation were comparable across groups with no differences between PDE and NE groups. In unadjusted mediation analyses, cortisol reactivity mediated the association between PDE and BASC II aggression scores (95% bootstrap confidence interval [CI], 0.04–4.28), externalizing problems scores (95% bootstrap CI, 0.03–4.50), and drug experimentation (95% bootstrap CI, 0.001–0.54). The associations remain with the inclusion of gender as a covariate but not when age is included.

Conclusion:

Findings support and expand current research in cortisol reactivity and PDE by demonstrating that cortisol reactivity attenuates the association between PDE and behavioral problems (aggression) and drug experimentation. If replicated, PDE may have long-lasting effects on stress-sensitive physiological mechanisms associated with behavioral problems (aggression) and drug experimentation in adolescence.
Hormonal influence on the effect of mirabegron treatment for overactive bladder
Authors: Kallner Helena Kopp , Elmér Caroline , Andersson Karl-Erik , Altman Daniel
Published: August 2016

Objective:

The aim of this study was to evaluate if levels of gonadotropic and sex steroidal hormones influence the efficacy of mirabegron in the treatment of overactive bladder.

Methods:

We included 58 female participants who received treatment with mirabegron 50 mg once daily and provided a blood sample for hormone profiling before treatment was initiated. Serum hormone concentrations for estradiol, progesterone, testosterone, FSH, LH, TSH, and T4 were analyzed. Urinary Distress Inventory (UDI), (overactive bladder domain: UDIOAB), and the short form Pelvic Floor Impact Questionnaire (PFIQ-7) were used to assess subjective outcomes.

Results:

There were significant overall improvements in UDI, UDIOAB, and the PFIQ from baseline to the 2 months of follow-up (P = 0.001, 0.001, and 0.008, respectively). The magnitude of the mean difference of improvements was similar between pre- and postmenopausal women. Estrogen levels were nonsignificantly lower in participants who experienced an improvement in UDI and UDIOAB at 2 months of follow-up as compared with those that did not (P = 0.7). There were no other clinically relevant differences in hormone levels in relation to improvements in UDI, UDIOAB, or PFIQ. In logistic regression analysis there were no associations between UDIOAB outcomes and age, previous use of anticholinergic drugs, parity, menopause, and local estrogen treatment.

Conclusions:

Estradiol, gonadotropic hormones, thyroid hormones, and testosterone levels did not influence the clinical effects of mirabegron in women with overactive bladder. Menopause status should not be a determinant for mirabegron treatment.
Longitudinal assessment of marrow fat content using three-point Dixon technique in osteoporotic rabbits
Authors: Li Guanwu , Xu Zheng , Chen Yilei , Chang Shixin , Calimente Horea , Hu Jiani , Wu Dongmei
Published: August 2016

Objective:

In this longitudinal pilot study, we aimed to investigate the intra-, interobserver, and scan-rescan reproducibility of marrow fat fraction (FF) measurements using three-point Dixon imaging in osteoporotic rabbits: comparison with histopathology.

Methods:

Twenty female rabbits were randomly assigned to sham-operation and ovariectomy in combination with daily methylprednisolone hemisuccinate groups (n = 10 per group). Marrow FF by three-point Dixon technique and bone density by dual-energy x-ray absorptiometry were assessed at baseline, 6 and 12 weeks after operation. Intra-, inter-reader, and scan-rescan reliability of FF measurements were evaluated using intraclass correlation coefficient (ICC) and Bland-Altman 95% limit of agreement. Histomorphometry was performed to quantify marrow adipocyte parameters.

Results:

Intra- and inter-reader reproducibility of FF measurements was “substantial” (ICC = 0.984 and 0.978, respectively). Although the ICC for scan-rescan reliability was excellent (ICC = 0.962), increased measurement variability was observed using Bland-Altman plot. Relative to the sham-operated rabbits, the adipocytes mean diameter, density, and percent adipocytes area in the osteoporotic rabbits increased by 23.4%, 68.9%, and 117.0%, respectively. Marrow FF was positively correlated with the quantitative parameters of adipocytes, particularly with percent adipocyte area, but inversely associated with bone density. At the relatively early stage, the percentage of bone loss was similar to that of elevated fatty marrow in the osteoporotic rabbits; at the later stage, the change for the latter outweighed that of the former.

Conclusions:

Results of three-point Dixon technique demonstrated a very reproducible manner within and between observers and acceptable scan-rescan performance in the assessment of marrow fat in rabbits.
Hydrogel Delivery of Mesenchymal Stem Cell–Expressing Bone Morphogenetic Protein-2 Enhances Bone Defect Repair
Authors: Hsiao Hui-Yi , Yang Shu-Rui , Brey Eric M. , Chu I-Ming , Cheng Ming-Huei
Published: August 2016

Background:

The application of bone tissue engineering for repairing bone defects has gradually shown some satisfactory progress. One of the concerns raising scientific attention is the poor supply of growth factors. A number of growth factor delivery approaches have been developed for promoting bone formation. However, there is no systematic comparison of those approaches on efficiency of neobone formation. In this study, the approaches using periosteum, direct supply of growth factors, or gene transfection of growth factors were evaluated to determine the osteogenic capacity on the repair of bone defect.

Methods:

In total, 42 male 21-week-old Sprague-Dawley rats weighing 250 to 400 g were used as the bone defect model to evaluate the bone repair efficiency. Various tissue engineered constructs of poly(ethylene glycol)-poly(l-lactic acid) (PEG-PLLA) copolymer hydrogel with periosteum, with external supply of bone morphogenetic protein-2 (BMP2), or with BMP2-transfected bone marrow–derived mesenchymal stem cells (BMMSCs) were filled in a 7-mm bone defect region. Animals were euthanized at 3 months, and the hydrogel constructs were harvested. The evaluation with histological staining and radiography analysis were performed for the volume of new bone formation.

Results:

The PEG-PLLA scaffold with BMMSCs promotes bone regeneration with the addition of periosteum. The group with BMP2-transfected BMMSCs demonstrated the largest volume of new bone among all the testing groups.

Conclusions:

Altogether, the results of this study provide the evidence that the combination of PEG-PLLA hydrogels with BMMSCs and sustained delivery of BMP2 resulted in the maximal bone regeneration.
Treatment of Suture-related Complications of Buried-suture Double-eyelid Blepharoplasty in Asians
Authors: Mizuno Tsutomu
Published: August 2016

Background:

Double-eyelid blepharoplasty is a popular aesthetic surgery in Asians. However, the buried suture technique is associated with complications related to implantation of the suture thread. The present study was performed to identify optimal surgical suture removal techniques in Japanese patients with suture-related complications after buried suture double-eyelid blepharoplasty.

Methods:

This retrospective study included 210 upper eyelids of 116 consecutive Japanese patients who had undergone buried suture double-eyelid blepharoplasty at other clinics. All patients underwent suture removal surgery at the author's institution for treatment of suture-related complications. Although 12 patients (10.3%) underwent suture removal surgery alone, 104 (89.7%) underwent secondary double-eyelid blepharoplasty. The outcomes of 3 techniques were evaluated: the small skin incision method, the full skin incision method, and the conjunctival method.

Results:

The small skin incision method was performed in 46 patients, the full skin incision method in 63, and the conjunctival method in 7. The success rate of the full skin incision method was significantly higher than that of the small skin incision method (4.8% vs 37.0%, respectively; p < 0.0001). Patients with an uncomfortable pulling sensation exhibited a linear scar or depressive deformity without inflammation of the tarsal plate and impingement on the subconjunctival capillary vessels of the tarsal plate or a depressive deformity of the levator muscle. Patients with corneal irritation exhibited chronic inflammation of the conjunctival surface of the tarsal plate.

Conclusions:

Suture-related complications of buried suture double-eyelid blepharoplasty in Asians must be treated with suture removal surgery. The full skin incision method is more reliable than the small incision method for such patients.
The Influence of Palatoplasty on Eating Function
Authors: Fujikawa Heishiro , Wakami Satoki , Motomura Hisashi
Published: August 2016

Postoperative dietary control and surgical procedures are important for minimizing complications after a palatoplasty because the palate is always exposed to stresses by various movements associated with eating. Currently, we provide fluid foods (food paste, liquid food, and soft food) to postpalatoplasty patients. However, nutritional inadequacies associated with fluid food necessitate the need to develop a new food specifically for postpalatoplasty patients. Although evaluating the influence of a palatoplasty on eating function is important for the development of a new diet, no data have been published on this topic. Thus, to evaluate the influence of a palatoplasty on eating function, we analyzed postoperative changes in the eating condition of cleft palate patients. We performed a retrospective study. All participants had undergone surgery for a cleft palate at our hospital. Nurses recorded the amount of food that patients consumed as a ratio of the whole meal, and we extracted data on the food type and the amount consumed at each meal from their medical records. After the ratio was expressed as a percentage of the whole meal (eating rate), we calculated the mean value of the percentage of the subject group and examined chronological changes. The eating rate was very low on postoperative day 1, it improved over time and was constant on postoperative day 7. From this result, we concluded that palatoplasty greatly influences the eating function of patients, and the influence lasts for at least a week after surgery.
Internal Pudendal Artery Perforator Island Flap for Management of Recurrent Benign Rectovaginal Fistula
Authors: Khalil Haitham H. , Malahias Marco N. , Karandikar Sharad , Hendrickse Charles
Published: August 2016

The management of recurrent rectovaginal fistula after obstetric injury and cryptoglandular sepsis is considered a major surgical challenge. The fistula poses a significant negative psychosocial and sexual morbidity. In addition, the poor quality of local tissues due to previous attempts at surgical repair adds to this challenge. There are few data regarding the management of persistent or recurrent fistula in the literature; however, several studies reported high failure rates after 2 or more procedures. We present 4 cases managed successfully in a multidisciplinary approach involving fistulectomy and immediate reconstruction with an internal pudendal artery perforator island flap.
Systematic Review and Operative Technique of Recalcitrant Pressure Ulcers Using a Fillet Flap Technique
Authors: McCarthy James E. , Rao Venkat K.
Published: August 2016

Background:

The purpose of this article is to describe the indications, operative technique, outcomes, and systematic review of the literature on the reconstruction of patients with end-stage pressure ulcers using a fillet flap technique. In this technique, the femur, tibia, and fibula are removed from the thigh and leg, and the soft tissue is used as a pedicled, or free, myocutaneous flap for reconstruction. Long-term outcomes, salient surgical technique of flap elevation, and design are detailed for patients who had a fillet of leg flap for reconstruction of extensive pressure ulcers.

Methods:

The indications, surgical technique, and postoperative outcomes of 5 patients who had pedicled fillet flaps are reviewed including patient age, sex, underlying comorbidities, duration of paraplegia, operative technique, and complications. A systematic review of the literature was performed searching PubMed, Cochrane Database, and Medline with the following MeSH terms: pressure ulcer, pressure sore, decubitus ulcer, fillet flap, and fillet flap. Inclusion criteria were use of a fillet technique, article data on the number of reconstructions before fillet flap, complications, and English language.

Results:

Most of our patients were male 75% (n = 3) with an average age of 47.5 years, had been paralyzed for an average of 16 years, and had few medical comorbidities. Two patients (3 flaps) required hip disarticulation, 1 patient had a bilateral fillet flaps, and 3 patients had resection of tibia/fibula. After following patients for an average of 1.4 years (4 mo to 2 yr), complications were limited to 1 patient who had partial-thickness flap loss at the distal skin flap that healed by secondary intention and 1 patient who had ulcer recurrence because of noncompliance. Four articles met inclusion criteria for systematic review and 3 were excluded.

Conclusions:

The fillet of leg flap remains a useful and reliable method of reconstructing end-stage pressure ulcers.
Right Ventricular Assist Device Configuration for Remote Decannulation
Authors: Tchantchaleishvili Vakhtang , Sagebin Fabio , Massey Howard Todd
Published: August 2016

Preoperative risk factors, intraoperative fluid shifts, and transfusions place patients at increased risk for right ventricular failure during left ventricular assist device implantation. Despite aggressive use of inotropes and pulmonary vasodilators, in severe cases of RV failure, a right ventricular assist device may be required. For the past several years, we have been implanting right ventricular assist devices in the presented configuration, allowing less invasive removal without sternotomy. The method is presented herein.
Treatment Patterns and Antipsychotic Medication Adherence Among Commercially Insured Patients With Schizoaffective Disorder in the United States
Authors: Joshi Kruti , Lin Jay , Lingohr-Smith Melissa , Fu Dong-Jing , Muser Erik
Published: August 2016

This study assessed real-world treatment patterns and antipsychotic (AP) medication adherence among commercially insured US patients with schizoaffective disorder (SCA). Continuously insured adults aged 18 years or older with a diagnosis of SCA from January 1, 2009, to December 31, 2012, were identified from the Clinformatics Data Mart database. Patients were categorized into 2 cohorts: incident or prevalent SCA. Demographics and clinical characteristics were evaluated during the baseline period. Use of psychiatric medications and adherence to AP medications were evaluated during a 12-month follow-up period after index diagnosis of SCA. Of the overall study population (N = 2713; mean age, 40.2 y; 52.7% female), 1961 patients (72.3%) (mean age, 38.7 y; 51.3% female) had incident SCA, and 752 patients (27.7%) (mean age, 43.9 y; 56.5% female) had prevalent SCA. Antipsychotics were used by 74.8% of patients in the overall study population during the follow-up period. The most commonly prescribed oral AP was risperidone (23.9%), followed by quetiapine (21.4%) and aripiprazole (20.4%). Use of any long-acting injectable APs in the overall study population during the follow-up period was less than 3%. A total of 49.0% and 38.0% of the overall study population had medication possession ratios and proportion of days covered for APs of 80% or greater, respectively. Overall use of long-acting injectable APs for the treatment of SCA is low, and adherence to AP medications, measured by both medication possession ratio and proportion of days covered, is suboptimal among patients with SCA in the real-world setting.
Transforming Nursing Education With Apple Technology
Authors: Clark Angela , Glazer Greer , Edwards Christopher , Pryse Yvette
Published: August 2016

The widespread adoption of technology has the potential to redefine nursing education. Currently, there is limited knowledge of how to implement technological advancements in nursing curricula. This article describes 1 college's journey to transform nursing education through leadership, professional development, and innovative learning and teaching. The iPad opens the classroom experience to resources and learning opportunities for students. Facilitating the culture change required to adopt the iPad as a teaching and learning tool required a supportive vision, strong leadership, commitment to provide adequate technological support, early adopters, and planning.
Cataract and Depressive Symptoms among Older Chinese Adults
Authors: Wang Haifang , Sun Hong-Peng , Wang Pei , Xu Yong , Pan Chen-Wei
Published: August 2016

Purpose

We aimed to assess the association of age-related cataract, a common eye condition in older people, with the presence of depressive symptoms in a community-based cohort of Chinese adults after controlling for a wide range of confounders.

Methods

A community-based survey of 4611 Chinese adults aged 60 years or older was conducted. Depressive symptoms were measured using the 9-item Patient Health Questionnaire (PHQ-9) depression scale in 4597 study participants whereas age-related cataracts were graded clinically using the Lens Opacities Classification System (LOCS) III scheme. The presence of depressive symptoms was defined as a PHQ-9 score from 5 to 27. Binary logistic regression models were fitted to calculate the odds ratios and 95% confidence intervals for the association between the age-related cataract and depressive symptoms.

Results

After adjusting for age, gender, educational level, monthly income, living alone, smoking, alcohol intake, tea consumption, sleeping hours per day, and presenting visual acuity, adults with cataract had higher odds of having depressive symptoms compared with those without (odds ratio = 1.33; 95% confidence interval 1.08, 1.70). There were no significant differences in the risk of depressive symptoms between those with bilateral and unilateral cataract. Adults with nuclear cataract had the greatest odds of having depressive symptoms among all cataract subtypes. Cataract patients with less education had greater odds of having depressive symptoms compared to those with higher levels of education.

Conclusions

Age-related cataract was related to the presence of depressive symptoms among older adults, particularly in poorly educated ones. This observed association was independent of poor vision and other potential confounders. It may be recommended that efforts and resources be channeled towards the surgical treatment programs of cataract in depressive adults.
What Public Policies Should Be Developed to Deal with the Epidemic of Myopia?
Authors: Morgan Ian G.
Published: August 2016

Developed countries in East and Southeast Asia are now faced with a high prevalence of high myopia in young adults, and this trend is emerging in other parts of the world. This is likely to lead to increased levels of pathological myopia. Fortunately, several school-based clinical trials have demonstrated that interventions based on increasing the amount of time that children spend outdoors can significantly slow the onset of myopia. I argue that it is time to implement mandatory programs of this kind in school systems, within a framework of regular monitoring of visual acuity, so that those children who become myopic are referred for clinical treatment as soon as possible to slow progression of their myopia towards high and potentially pathological myopia.
What Public Policies Should Be Developed to Cope with the Myopia Epidemic?
Authors: Verkicharla Pavan Kumar , Chia Nadine En Hui , Saw Seang-Mei
Published: August 2016

The epidemic of myopia in urban Asian cities has increased over recent generations and has become a significant public health concern. Considering the potential role of time outdoors in myopia prevention, and the differences in behavioral attitudes of individuals living in Urban East Asian (more indoor-centric) and Western countries, public policies should be developed in different countries accordingly to encourage children to go outdoors to counteract myopia. This is a short manuscript (presented at the International Myopia Conference—2015 by Prof. Seang Mei Saw) about public policies that should be developed to cope with the “myopia epidemic.”
Epstein–Barr Virus Neuroretinitis in a Lung Transplant Patient
Authors: Hsia Yen C. , Chin-Hong Peter V. , Levin Marc H.
Published: August 2016

Epstein–Barr virus (EBV)-associated optic neuropathy is rare with few reported cases, mostly involving immunocompetent patients who developed optic nerve involvement after infectious mononucleosis. We describe a unique case of a patient who developed severe bilateral EBV neuroretinitis after solid organ transplant.
“Salt and Pepper” Pontine Infarct
Authors: Lyons Lance J. , Law Susan W. , Kubie John L.
Published: August 2016

A paramedian pontine stroke may herald the unique symptom of “salt and pepper” eye pain, in which patients describe the sensation of pepper rubbed into the eye. While localization of the lesion is a common thread among published cases, the mechanism for the sensation of eye pain is still a matter of conjecture. It is important for clinicians to be aware of this unique symptom because strokes rarely present with eye pain and failure to establish this diagnosis might lead to a poor clinical outcome.
Highly parallel direct RNA sequencing on an array of nanopores
Authors: Garalde Daniel R. , Snell Elizabeth A. , Jachimowicz Daniel , Heron Andrew J. , Bruce Mark , Lloyd Joseph , Warland Anthony , Pantic Nadia , Admassu Tigist , Ciccone Jonah , Serra Sabrina , Keenan Jemma , Martin Samuel , McNeill Luke , Wallace Jayne , Jayasinghe Lakmal , Wright Chris , Blasco Javier , Sipos Botond , Young Stephen , Juul Sissel , Clarke James , Turner Daniel J
Published: August 2016

Ribonucleic acid sequencing can allow us to monitor the RNAs present in a sample. This enables us to detect the presence and nucleotide sequence of viruses, or to build a picture of how active transcriptional processes are changing – information that is useful for understanding the status and function of a sample. Oxford Nanopore Technologies’ sequencing technology is capable of electronically analysing a sample’s DNA directly, and in real-time. In this manuscript we demonstrate the ability of an array of nanopores to sequence RNA directly, and we apply it to a range of biological situations. Nanopore technology is the only available sequencing technology that can sequence RNA directly, rather than depending on reverse transcription and PCR. There are several potential advantages of this approach over other RNA-seq strategies, including the absence of amplification and reverse transcription biases, the ability to detect nucleotide analogues and the ability to generate full-length, strand-specific RNA sequences. Direct RNA sequencing is a completely new way of analysing the sequence of RNA samples and it will improve the ease and speed of RNA analysis, while yielding richer biological information.
Evo-engineering and the Cellular and Molecular Origins of the Vertebrate Spinal Cord
Authors: Steventon Ben , Arias Alfonso Martinez
Published: August 2016

The formation of the spinal cord during early embryonic development in vertebrate embryos is a continuous process that begins at gastrulation and continues through to the completion of somitogenesis. Despite the conserved usage of patterning mechanisms and gene regulatory networks that act to generate specify spinal cord progenitors, there now exists two seemingly disparate models to account for their action. In the first, a posterior localized signalling source transforms previously anterior-specified neural plate into the spinal cord. In the second, a population of bipotent stem cells undergo continuous self-renewal and differentiation to progressively lay down the spinal cord and axial mesoderm by posterior growth. Whether this represents fundamental differences between the experimental model organisms utilised in the generation of these models remains to be addressed. Here we review lineage studies across four key vertebrate models: mouse, chicken,Xenopusand zebrafish and relate this to the underlying gene regulatory networks that are known to be required for spinal cord formation. We propose that by applying a dynamical systems approach to understanding how distinct neural and mesodermal fates arise from a bipotent progenitor pool, it is possible to begin to understand how differences in the dynamical cell behaviours such as proliferation rates and cell movements can map onto conserved regulatory networks to generate diversity in the timing of tissue generation and patterning during development.
Planning horizon affects prophylactic decision-making and epidemic dynamics
Authors: Nardin Luis G. , Miller Craig R. , Ridenhour Benjamin J. , Krone Stephen M. , Joyce Paul , Baumgaertner Bert O.
Published: August 2016

Human behavior can change the spread of infectious disease. There is limited understanding of how the time in the future over which individuals make a behavioral decision, their planning horizon, affects epidemic dynamics. We developed an agent-based model (along with an ODE analog) to explore the decision-making of self-interested individuals on adopting prophylactic behavior. The decision-making process incorporates prophylaxis efficacy and disease prevalence with individuals' payoffs and planning horizon. Our results show that for short and long planning horizons individuals do not consider engaging in prophylactic behavior. In contrast, individuals adopt prophylactic behavior when considering intermediate planning horizons. Such adoption, however, is not always monotonically associated with the prevalence of the disease, depending on the perceived protection efficacy and the disease parameters. Adoption of prophylactic behavior reduces the peak size while prolonging the epidemic and potentially generates secondary waves of infection. These effects can be made stronger by increasing the behavioral decision frequency or distorting an individual’s perceived risk of infection.
Physical model of the genotype-to-phenotype map of proteins
Authors: Tlusty Tsvi , Libchaber Albert , Eckmann Jean-Pierre
Published: August 2016

How DNA is mapped to functional proteins is a basic question of living matter. We introduce and study a physical model of protein evolution which suggests a mechanical basis for this map. Many proteins rely on large-scale motion to function. We therefore treat protein as learning amorphous matter that evolves towards such a mechanical function: Genes are binary sequences that encode the connectivity of the amino acid network that makes a protein. The gene is evolved until the network forms a shear band across the protein, which allows for long-range, soft modes required for protein function. The evolution reduces the high-dimensional sequence space to a low-dimensional space of mechanical modes, in accord with the observed dimensional reduction between genotype and phenotype of proteins. Spectral analysis of the space of 106solutions shows a strong correspondence between localization around the shear band of both mechanical modes and the sequence structure. Specifically, our model shows how mutations are correlated among amino acids whose interactions determine the functional mode.

PACS numbers: 87.14.E-, 87.15.-v, 87.10.-e
Reward learning deficits in Parkinson’s disease depend on depression
Authors: Timmer Monique H.M. , Sescousse Guillaume , van der Schaaf Marieke E. , Esselink Rianne A.J. , Cools Roshan
Published: August 2016

Background

Depression is one of the most common and debilitating non-motor symptoms of Parkinson’s disease (PD). The neurocognitive mechanisms underlying depression in PD are unclear and treatment is often suboptimal.

Methods

We investigated the role of striatal dopamine in reversal learning from reward and punishment by combining a controlled medication withdrawal procedure with functional magnetic resonance imaging (fMRI) in 22 non-depressed PD patients and 19 PD patients with past or present PD-related depression.

Results

PD patients with a PD-related depression (history) exhibited impaired reward versus punishment reversal learning as well as reduced reward versus punishment-related BOLD signal in the striatum (putamen) compared with non-depressed PD patients. No effects of dopaminergic medication were observed.

Conclusions

The present findings demonstrate that impairments in reversal learning from reward versus punishment and associated reward-related striatal signalling depend on the presence of (a history of) depression in PD.
ARGLU1 is a Glucocorticoid Receptor Coactivator and Splicing Modulator Important in Stress Hormone Signaling and Brain Development
Authors: Magomedova Lilia , Tiefenbach Jens , Zilberman Emma , Voisin Veronique , Robitaille Melanie , Gueroussov Serge , Irimia Manuel , Ray Debashish , Patel Rucha , Xu ChangJiang , Jeyasuria Pancharatnam , Bader Gary D. , Hughes Timothy R. , Krause Henry , Blencowe Benjamin J. , Angers Stephane , Cummins Carolyn L.
Published: August 2016

Prolonged exposure to glucocorticoid stress hormones precipitates mood and cognitive disorders. We identified arginine and glutamate rich 1 (ARGLU1) in a screen for new modulators of glucocorticoid signaling in the CNS. Biochemical studies found that the glutamate rich C-terminus coactivates the glucocorticoid receptor (GR) and the arginine rich N-terminus interacts with splicing factors and RNA. RNA-seq of neuronal cells ±siARGLU1found significant changes in the expression and alternative splicing of distinct genes involved in neurogenesis. Loss of ARGLU1 was embryonic lethal in mice, and knockdown in zebrafish caused neurodevelopmental and heart defects. Treatment with dexamethasone, a GR activator, also induced changes in the pattern of alternatively spliced genes, highlighting an underappreciated global mechanism of glucocorticoid action in neuronal cells. Thus, in addition to its basal role, ARGLU1 links glucocorticoid-mediated transcription and alternative splicing in neural cells, providing new avenues from which to investigate the molecular underpinnings of cognitive stress disorders.
Low-pH induced reversible reorganizations of chloroplast thylakoid membranes - as revealed by small-angle neutron scattering
Authors: Ünnep Renáta , Zsiros Ottó , Hörcsik Zsolt , Markó Márton , Jajoo Anjana , Kohlbrecher Joachim , Garab Győző , Nagy Gergely
Published: August 2016

Energization of thylakoid membranes brings about the acidification of the lumenal aqueous phase, which activates important regulatory mechanisms. Earlier Jajoo and coworkers (2014 FEBS Lett. 588:970) have shown that low pH in isolated plant thylakoid membranes induces changes in the excitation energy distribution between the two photosystems. In order to elucidate the structural background of these changes, we used small-angle neutron scattering on thylakoid membranes exposed to low p2H and show that gradually lowering the p2H from 8.0 to 5.0 causes small but well discernible reversible diminishment of the periodic order and the lamellar repeat distance and an increased mosaicity – similar to the effects elicited by light-induced acidification of the lumen. Our data strongly suggest that thylakoids dynamically respond to the membrane energization and actively participate in different regulatory mechanisms.

Highlights

Thylakoid membranes exposed to low p2H studied by small-angle neutron scattering

Acidification causes reversible shrinkage and diminished lamellar order

SANS changes induced by low pH resemble those due to light-induced lumenal acidification

Abbreviations

NPQ

non-photochemical quenching

qE

the energy-dependent component of NPQ

ΔμH+

transmembrane electrochemical potential gradient

PSI

photosystem I

PSII

photosystem II

LET

linear electron transport

CD

circular dichroism

SANS

small-angle neutron scattering

q

scattering vector or momentumtransfer

I

intensity

q*

center position of the Bragg peak

RD

repeat distance

φ

azimuthal angle

I(φ)

angular dependency of the scattering intensity

FWHM

full width at half maximum
3-5 Hz membrane potential oscillations decrease the gain of neurons in visual cortex
Authors: Einstein Michael C. , Polack Pierre-Olivier , Golshani Peyman
Published: August 2016

Gain modulation is a computational mechanism critical for sensory processing. Yet, the cellular mechanisms that decrease the gain of cortical neurons are unclear. To test if low frequency subthreshold oscillations could reduce neuronal gain during wakefulness, we measured the membrane potential of primary visual cortex (V1) layer 2/3 excitatory, parvalbumin-positive (PV+), and somatostatin-positive (SOM+) neurons in awake mice during passive visual stimulation and sensory discrimination tasks. We found prominent 3-5 Hz membrane potential oscillations that reduced the gain of excitatory neurons but not the gain of PV+ and SOM+ interneurons, which oscillated synchronously with excitatory neurons and fired strongly at the peak of de polarizations. 3-5 Hz oscillation prevalence and timing were strongly modulated by visual input and the animal’s behavior al response, suggesting that these oscillations are triggered to adjust sensory responses for specific behavioral contexts. Therefore, these findings reveal a novel gain reduction mechanism that adapts sensory processing to behavior.
Dynamic representation of time in brain states
Authors: Bueno Fernanda Dantas , Morita Vanessa C. , Camargo Raphael Y. de , Reyes Marcelo B. , Caetano Marcelo S. , Cravo André M.
Published: August 2016

The ability to process time on the scale of milliseconds and seconds is essential for behaviour. A growing number of studies have started to focus on brain dynamics as a mechanism for temporal encoding. Although there is growing evidence in favour of this view from computational andin vitrostudies, there is still a lack of results from experiments in humans. We show that high-dimensional brain states revealed by multivariate pattern analysis of human EEG are correlated to temporal judgements. First, we show that, as participants estimate temporal intervals, the spatiotemporal dynamics of their brain activity are consistent across trials. Second, we present evidence that these dynamics exhibit properties of temporal perception, such as the scalar property. Lastly, we show that it is possible to predict temporal judgements based on brain states. These results show how scalp recordings can reveal the spatiotemporal dynamics of human brain activity related to temporal processing.
Gene-culture co-inheritance of a behavioral trait
Authors: Aguilar Elliot G. , Akçay Erol
Published: August 2016

Human behavioral traits are complex phenotypes that result from both genetic and cultural transmission. But different inheritance systems need not favor the same phenotypic outcome. What happens when there are conflicting selection forces in the two domains? To address this question, we derive a Price equation that incorporates both cultural and genetic inheritance of a phenotype where the effects of genes and culture are additive. We then use this equation to investigate whether a genetically maladaptive phenotype can evolve under dual transmission. We examine the special case of altruism using an illustrative model, and show that cultural selection can overcome genetic selection when the variance in culture is sufficiently high with respect to genes. Finally, we show how our basic result can be extended to non-additive effects models. We discuss the implications of our results for understanding the evolution of maladaptive behaviors.
phyC: Clustering cancer evolutionary trees
Authors: Matsui Yusuke , Niida Atsushi , Uchi Ryutaro , Mimori Koshi , Miyano Satoru , Shimamura Teppei
Published: August 2016

Motivation

Multi-regional sequencing provides new opportunities to investigate genetic heterogeneity within or between common tumors from an evolutionary perspective. Several state-of-the-art methods have been proposed for reconstructing cancer sub-clonal evolutionary trees based on multi-regional sequencing data to develop models of cancer evolution. However, the methods developed thus far are not sufficient to characterize and interpret the diversity of cancer sub-clonal evolutionary trees.

Results

We propose a clustering method (phyC) for cancer sub-clonal evolutionary trees, in which sub-groups of the trees are identified based on topology and edge length attributes. For interpretation, we also propose a method for evaluating the diversity of trees in the clusters, which provides insight into the acceleration of sub-clonal expansion. Simulation showed that the proposed method can detect true clusters with sufficient accuracy. Application of the method to actual multi-regional sequencing data of clear cell renal carcinoma and non-small cell lung cancer allowed for the detection of clusters related to cancer type or phenotype.

Availability

phyCis implemented with R(>=3.2.2) and is available fromhttps://github.com/ymatts/phyC.

Contact

ymatsui@med.nagoya-u.ac.jp
A Single Nucleotide Resolution Model for Large-Scale Simulations of Double Stranded DNA
Authors: Fosado Y. A. G. , Michieletto D. , Allan Jim , Brackley Chris , Henrich O. , Marenduzzo D.
Published: August 2016

The computational modelling of DNA is becoming crucial in light of new advances in DNA nanotechnology, single-molecule experiments andin vivoDNA tampering. Here we present a mesoscopic model for double stranded DNA (dsDNA) at the single nucleotide level which retains the characteristic helical structure, while being able to simulate large molecules — up to a million base pairs — for time-scales which are relevant to physiological processes. This is made possible by an efficient and highly-parallelised implementation of the model which we discuss here. We compare the behaviour of our model with single molecule experiments where dsDNA is manipulated by external forces or torques. We also present some results on the kinetics of denaturation of linear DNA.
Engaging patients in antimicrobial resistance and stewardship
Authors: Popescu Ioana , Neudorf Kim , Kossey Sandi N.
Published: August 2016

Purpose

– The purpose of this paper is to provide an overview of the perspectives of patient advisors (PAs) on the current state of antimicrobial resistance (AR) and stewardship in Canada and identifies next steps, with the goal of stimulating further collaboration for action between leaders and PAs as well as research.

Design/methodology/approach

– The perspectives of PAs were gathered using an electronic online survey of 72 respondents. A search of peer reviewed literature and publicly available reports informed the development of the survey and the articulation of a more comprehensive viewpoint in this paper.

Findings

– PAs view AR as a serious and growing public health threat. They believe sharing the responsibility for infection prevention and control and antimicrobial stewardship will help to control the problem. They see healthcare professionals as the most appropriate stakeholders to influence behaviors associated with appropriate antibiotic use, however, they also see value in public campaigns. Importantly, they identify several opportunities for PA contribution: education of care providers, patients, families, and the public; co-design and development of materials, policies, improvement initiatives, and research; and participation in and promotion of public campaigns.

Practical implications

– Engaging PAs as partners at all system levels is becoming common practice. PAs bring a unique and complementary perspective that could contribute to antimicrobial stewardship efforts.

Originality/value

– This paper begins to bridge a gap between literature and practice, and proposes that PAs can contribute to antimicrobial stewardship efforts.
Antimicrobial stewardship: Australia
Authors: Spigelman Allan D. , Rendalls Shane , McLaws Mary-Louise , Gray Ashleigh
Published: August 2016

Purpose

– The purpose of this paper is to provide an overview of the context for strategies to overcome antimicrobial resistance in Australia, which may provide valuable learnings for other jurisdictions.

Design/methodology/approach

– Non-systematic review of literature from websites of national, state and territory health departments and interviews with key stakeholders for Australian strategies to reduce antimicrobial resistance.

Findings

– In July 2015 all states and territories in Australia adopted the National Antimicrobial Resistance Strategy 2015-2019, which is built on the World Health Organization policy package to combat antimicrobial resistance. This strategy represents “the collective, expert views of stakeholders on how best to combat antimicrobial resistance in Australia. It will also support global and regional efforts, recognising that no single country can manage the threat of antimicrobial resistance alone”. It combines quantitative and qualitative monitoring strategies with frameworks and guidelines to improve management of the use of antimicrobial resistant drugs. Prior to this, health services and states developed and implemented initiatives aimed at monitoring and improving prescribing practices. Development of the national strategy has encouraged and fostered debate within the Australian health system and a raft of new policy initiatives.

Research limitations/implications

– Surveillance strategies are in place to monitor impact and trends at jurisdictional and sector levels. However, actual impact on antimicrobial resistance and prescribing practices remains to be seen as existing initiatives are expanded and new initiatives implemented.

Practical implications

– This overview of key Australian initiatives balancing quantitative and qualitative surveillance, accreditation, research, education, community awareness and price signals on antibiotic prescribing practices may be valuable to health systems in developing local strategies.

Originality/value

– The authors provide an up to date overview of the context, strategies and aims of antimicrobial stewardship in Australia.