bluuebunny/crossref_metadata_2025 huggingface dataset:
Adverse effects of exposure to armed conflict on pregnancy: a systematic review
Authors: Keasley James , Blickwedel Jessica , Quenby Siobhan
Published: November 2017

Introduction

Exposure to armed conflict has manifold implications for both military and civilian populations. Prenatal stress has detrimental effects on both obstetric outcomes, fetal development and the development of an individual later in life. As well as causing stress to the mother, armed conflicts can decimate local infrastructures making it increasingly difficult to access antenatal and general healthcare. The present review is particularly salient in light of the many ongoing current conflicts. It examines the impacts of exposure to armed conflicts on the pregnancy outcomes.

Methods

A thorough literature search was carried out on three databases using MeSH and truncation terms. 13 studies were included in the final analysis relating to mothers exposed to armed conflicts since 1990.

Results

The studies include data from 1 172 151 patients: mothers from Libya, Bosnia, Herzegovina, Israel, Palestine, Kosovo, Yugoslavia, Nepal, Somalia, Iraq, Kuwait and Afghanistan. There is evidence of an increased risk of mothers giving birth to babies of low birth weight as reported in nine included studies. All have a degree of bias, with four at lower and five at higher risk of bias, either not adjusting for confounders or not employing robust measures of exposure to conflict. Further evidence suggested an increase in the incidence of miscarriage, stillbirth, prematurity, congenital abnormalities, miscarriage and premature rupture of membranes among mothers exposed to armed conflict.

Conclusion

Despite the varying degrees of bias which must be considered for the available evidence, the data with the lowest risk of bias suggest a relationship between exposure to armed conflict and low birth weight. In light of the current level of displacement experienced by such populations, the identification of pregnancies at risk could improve the efficacy of antenatal care. Clinicians should consider additional ultrasound scanning where appropriate to monitor for restricted growth in such pregnancies.
Challenges to discussing palliative care with people experiencing homelessness: a qualitative study
Authors: Hudson Briony F , Shulman Caroline , Low Joseph , Hewett Nigel , Daley Julian , Davis Sarah , Brophy Nimah , Howard Diana , Vivat Bella , Kennedy Peter , Stone Patrick
Published: November 2017

Objectives

To explore the views and experiences of people who are homeless and those supporting them regarding conversations and approaches to palliative care

Setting

Data were collected between October 2015 and October 2016 in homeless hostels and day centres and with staff from primary and secondary healthcare providers and social care services from three London boroughs.

Participants

People experiencing homelessness (n=28), formerly homeless people (n=10), health and social care providers (n=48), hostel staff (n=30) and outreach staff (n=10).

Methods

In this qualitative descriptive study, participants were recruited to interviews and focus groups across three London boroughs. Views and experiences of end-of-life care were explored with people with personal experience of homelessness, health and social care professionals and hostel and outreach staff. Saturation was reached when no new themes emerged from discussions.

Results

28 focus groups and 10 individual interviews were conducted. Participants highlighted that conversations exploring future care preferences and palliative care with people experiencing homelessness are rare. Themes identified as challenges to such conversations included attitudes to death; the recovery focused nature of services for people experiencing homelessness; uncertainty regarding prognosis and place of care; and fear of negative impact.

Conclusions

This research highlights the need for a different approach to supporting people who are homeless and are experiencing advanced ill health, one that incorporates uncertainty and promotes well-being, dignity and choice. We propose parallel planning and mapping as a way of working with uncertainty. We acknowledge that these approaches will not always be straightforward, nor will they be suitable for everyone, yet moving the focus of conversations about the future away from death and dying, towards the present and the future may facilitate conversations and enable the wishes of people who are homeless to be known and explored.
Lived experience of women with gestational diabetes mellitus living in China: a qualitative interview study
Authors: Ge Li , Wikby Kerstin , Rask Mikael
Published: November 2017

Objective

To explore the lived experience of women with gestational diabetes mellitus (GDM) living in China in order to add knowledge about how the Chinese women suffer from GDM.

Design

A qualitative interpretive interview study. Data were collected with a snowball sampling technique. Phenomenological hermeneutics was used as the analysis method based on Ricoeur’s phenomenological hermeneutical interpretation theory.

Setting

The study was performed at the participants’ work places, or at the obstetric clinics or wards at two provincial hospitals and one municipal hospital in the southeast of China.

Participants

Inclusion criteria were age ≥18 years, diagnosis of GDM without other pregnancy complications, in 34th gestational weeks—postpartum 4th weeks and speaking Mandarin Chinese without speech impediment. 62 women, who met the inclusion criteria, took part in the study.

Results

The lived experience of the women with GDM living in China was formulated into a main theme: ‘longing for caring care’. The main theme was derived from four themes: being stricken by GDM, wishing to receive caring GDM care, being left alone to struggle with GDM and trying to adjust and adapt to life with GDM.

Conclusion

The eagerness for caring care in China was highlighted. The lack of caring care could be one of the possible reasons why the professional–patient relations were deteriorating in China. It could be useful for health providers and health policymakers to receive education and training about caring care. Using the health metaphor of balance and ‘patient participation’ and ‘patient-centred’ approaches may benefit women with GDM and thus improve the quality of care in China.
Improving hearing and vision in dementia: protocol for a field trial of a new intervention
Authors: Regan Jemma , Dawes Piers , Pye Annie , Armitage Christopher J , Hann Mark , Himmelsbach Ines , Reeves David , Simkin Zoe , Yang Fan , Leroi Iracema
Published: November 2017

Introduction

Quality of life and other key outcomes may be improved by optimising hearing and vision function in people living with dementia. To date, there is limited research assessing the efficacy of interventions aimed at improving hearing and vision in people with dementia. Here, we outline a protocol to field test a newly developed home-based intervention, designed to optimise sensory functioning in people with dementia in three European sites. The results of this study will inform the design and conduct of a full-scale randomised controlled trial (RCT) in five European sites.

Methods and analysis

In this multisite, single arm, open label, feasibility study, participants with dementia (n=24) will be assessed for hearing and vision impairments and be prescribed a hearing aid and/or glasses. Each participant will have a study partner (‘dyads’). A subset of dyads will receive ‘sensory support’ from a ‘sensory support therapist’, comprising home visits over 12 weeks. The therapist will offer the following intervention: adherence support for corrective devices; adaptations to the home environment to facilitate sensory function; communication training; and referral to community-based support services. The primary outcomes will be process measures assessing the feasibility, tolerability and acceptability of: (1) the intervention components; (2) the method of implementation of the intervention and (3) the study procedures, including outcome assessment measures. Quantitative data will be collected at baseline and follow-up. Qualitative data using semistructured interviews will be collected postintervention and weekly, using participant diaries. Finally, we will explore a model of cost-effectiveness to apply in the subsequent full-scale trial. This feasibility study is a necessary step in the development of a complex, individualised, psychosocial intervention. The data gathered will allow logistical and theoretical processes to be refined in preparation for a full-scale RCT.

Ethics and dissemination

Ethical approval was obtained in all three participating countries. Results of the field trial will be submitted for publication in a peer-reviewed journal.
Late-stage left ventricular dysfunction in adult survivors of tetralogy of Fallot repair in childhood
Authors: Anabtawi Abdel , Mondragon Judith , Dodendorf Diane , Laskey Warren K
Published: November 2017

Objective

Left ventricular systolic dysfunction (LVSD) in adult survivors of tetralogy of Fallot (TOF) repair in childhood has been observed, although the relationship with long-term outcome remains inadequately described.

Methods

A cohort of 44 consecutive adult patients with TOF repair in childhood were followed prospectively from January 2001 through June 2016. LVSD was defined as an echocardiographically derived left ventricular (LV) ejection fraction <0.55. Clinical and demographic characteristics in patients with and without LVSD were compared. Event-free survival (all-cause death or hospitalisation) was estimated using the product limit method.

Results

The average time from childhood surgical repair to cohort inception was similar between groups (LVSD, 33.7±12.7 years; normal LV function, 36.1±14.9 years; P=0.62) as were their mean ages (LVSD, 36.5±14.5 years; normal LV function, 40.7±15.2 years; P=0.73). Patients with LVSD (n=13) had more prior surgeries, more frequent history of significant pulmonic regurgitation, right ventricular systolic dysfunction and more implantable cardiac devices. Over a total observation time of 15.5 years, patients with LVSD were at significantly higher risk of all-cause death or hospitalisation (P=0.006). Onset of LVSD frequently preceded an adverse outcome.

Conclusions

In this cohort of adult patients with TOF repair in childhood followed for a total of 550 patient-years, the frequency of LVSD was 30%. LVSD was associated with lower event-free survival. The appearance of LVSD many years after TOF repair may herald the onset of an adverse outcome.
Underwater faunal assemblages: radiocarbon dates and late Quaternary vertebrates from Cold Lake, Alberta and Saskatchewan, Canada
Authors: Jass Christopher N. , Caldwell Devyn , Barrón-Ortiz Christina I. , Beaudoin Alwynne B. , Brink Jack , Sawchuk Matthew
Published: November 2017

Late Quaternary faunal remains from three underwater settings in Cold Lake, Alberta and Saskatchewan, Canada, include at least 13 vertebrate taxa consistent with assemblages that postdate the Last Glacial Maximum (LGM). Seven new radiocarbon dates range from 10 350 ± 40 to 161 ± 23 years BP and provide insight into the post-LGM biotic history of east-central Alberta and west-central Saskatchewan. The presence of an essentially modern large mammal biota is suggested for the mid-Holocene, and possibly earlier, if the absence of extinct or extirpated taxa in association with Late Pleistocene Bison at the Alberta–Saskatchewan site is meaningful. Taphonomically, some of the remains suggest deposition in open environments during the Holocene, possibly when lake levels were lower. The recovery of late Quaternary faunal remains from a present-day lacustrine setting is novel, and suggests that similar records may occur in other lakes in western Canada, including those in areas with scarce Quaternary vertebrate records.
Fertilization increased leaf water use efficiency and growth of Pinus taeda subjected to five years of throughfall reduction
Authors: Samuelson Lisa J. , Kane Michael B. , Markewitz Daniel , Teskey Robert O. , Akers Madison K. , Stokes Tom A. , Pell Charles J. , Qi Ji
Published: November 2017

High productivity of fertilized loblolly pine (Pinus taeda L.) plantations in the southern United States is related to increased leaf area index (LAI), but higher evaporative leaf surface area may increase drought vulnerability. To determine if the benefits of fertilization are affected by water availability or the effects of drought are exacerbated by fertilization, the interactive effects of throughfall treatment (ambient throughfall versus throughfall reduction) and fertilization treatment (no fertilization versus one-time fertilization) on a loblolly pine plantation were examined over five growing seasons. Enhancement of LAI and growth from fertilization was unaffected by throughfall treatment, and reductions in LAI, tree height, and stand volume increment in response to throughfall reduction were unaffected by fertilization treatment. Leaf-level stomatal conductance (gS) was decreased and water use efficiency was increased by fertilization and by throughfall reduction. Lower gS was associated with decreased leaf predawn water potential in response to throughfall reduction. In contrast, lower gs in response to fertilization was associated with a reduction in the hydraulic allometry index, a measure of the ability of sapwood to supply water to leaves. These results suggest that fertilization may enhance LAI and growth even under mild or moderate drought.
U1 snDNA chromosomal mapping in ten spittlebug species (Cercopidade, Auchenorrhyncha, Hemiptera)
Authors: Anjos Allison , Paladini Andressa , Mariguela Tatiane C. , Cabral-de-Mello Diogo C.
Published: November 2017

Spittlebugs, which belong to the family Cercopidae (Auchenorrhyncha, Hemiptera), form a large group of xylem-feeding insects that are best known for causing damage to plantations and pasture grasses. The holocentric chromosomes of these insects remain poorly studied in regards to the organization of different classes of repetitive DNA. To improve chromosomal maps based on repetitive DNAs and to better understand the chromosomal organization and evolutionary dynamics of multigene families in spittlebugs, we physically mapped the U1 snRNA gene with fluorescence in situ hybridization (FISH) in 10 species of Cercopidae belonging to three different genera. All the U1 snDNA clusters were autosomal and located in interstitial position. In seven species, they were restricted to one autosome per haploid genome, while three species of the genus Mahanarva showed two clusters in two different autosomes. Although it was not possible to precisely define the ancestral location of this gene, it was possible to observe the presence of at least one cluster located in a small bivalent in all karyotypes. The karyotype stability observed in Cercopidae is also observed in respect to the distribution of U1 snDNA. Our data are discussed in light of possible mechanisms for U1 snDNA conservation and compared with the available data from other species.
INTERNAL MIGRATION RESTRICTIONS AND LABOR ALLOCATION IN DEVELOPING COUNTRIES
Authors: RANGAZAS PETER , WANG XIAOBING
Published: November 2017

We develop a simple model with endogenous rural–urban migration to analyze the implications of migration restrictions for economic welfare. The model reveals that a combination of an efficient urban bias in public service provision and internal migration restrictions can raise social welfare. Our results suggest that migration restrictions should be carefully assessed as a policy choice rather than immediately dismissed as suboptimal. However, even when restrictions raise social welfare, they increase urban households’ welfare at the expense of rural households’ welfare, creating an equity tradeoff for policy-makers to consider.
A Programmable IEEE 1500-Compliant Wrapper for Testing of Word-Oriented Memory Cores
Authors: Nourmandi-Pour Reza
Published: November 2017

In today’s embedded technology, memories are the universal components. With the onset of the deep-submicron VLSI technology, the density and capacity of the memory are growing. However, providing a cost-effective test solution for these on-chip memories is becoming a challenging task. As memory and other processing cores have been embedded deeply in system chips, the IEEE std 1500 has been suggested to facilitate the test of these core types. Whereas up to now this standard has not presented a definite solution for testing of memory cores, in this paper, we proposed a programmable IEEE 1500-compliant wrapper for applying several Mach algorithms on word-oriented memory cores to reach the desired fault coverage. The proposed wrapper is without finite-state-machine controller, and as a result, the complexity of wrapper circuitry is low and hardware redundancy is acceptable as well.
PREVENTING THE SPREAD OF SCHISTOSOMIASIS IN GHANA: POSSIBLE OUTCOMES OF INTEGRATED OPTIMAL CONTROL STRATEGIES
Authors: ZHANG HONG , HARVIM PRINCE , GEORGESCU PAUL
Published: November 2017

The goal of a future free from schistosomiasis in Ghana can be achieved through integrated strategies, targeting simultaneously several stages of the life cycle of the schistosome parasite. In this paper, the transmission of schistosomiasis is modeled as a multi-scale 12-dimensional system of ODEs that includes vector-host and within-host dynamics of infection. An explicit expression for the basic reproduction number [Formula: see text] is obtained via the next generation method, this expression being interpreted in biological terms, as well as in terms of reproductive numbers for each type of interaction involved. After discussing the stability of the disease-free equilibrium and the existence and uniqueness of the endemic equilibrium, the Center Manifold Theory is used to show that for values of [Formula: see text] larger than 1, but close to 1, the unique endemic equilibrium is locally asymptotically stable. A sensitivity analysis indicates that [Formula: see text] is most sensitive to the natural death rate of the vector population, while numerical simulations of optimal control strategies reveal that the most effective strategy for the control and possible elimination of schistosomiasis should combine sanitary measures (access to safe water, improved sanitation and hygiene education), large-scale treatment of infected population and vector control measures (via the use of molluscicides), for a significant amount of time.
Full spectrum of nonlinear Jaynes–Cummings and anti-Jaynes–Cummings models
Authors: Raffa Francesco A. , Rasetti Mario
Published: November 2017

The unitary transformation method is utilized for the closed form solution of the nonlinear generalization of the Jaynes–Cummings (JC) model, which includes arbitrary multiphoton and intensity-dependent interactions between radiation and matter. Specifically, the unitary transformation leading to the diagonalization of the relevant Hamiltonian is established and energy levels and eigenstates are derived. It is also shown that the results for the JC model can be extended to the anti-Jaynes–Cummings (AJC) model through the map between the two models.
A review and statistical assessment of the criteria for determining cave significance
Authors: Auler Augusto S. , Souza Tatiana A. R. , Sé Daniela C. , Soares Gustavo A.
Published: November 2017

Determining the significance of caves is challenging due to a lack of consensus on which parameters to consider and their relative importance, in addition to difficulties in applying the parameters in a repeatable way. However, classifying caves by levels of significance is unequivocally important because it allows the prioritization of caves for future environmental protection. In countries where the subsurface belongs to the government, such as Brazil, the decision process is coordinated at the government level and a comprehensive approach balancing environmental protection and economic/social interests should be applied. Brazil has the most comprehensive set of criteria for assessing the significance of caves, encompassing parameters applied in other countries. A sample of 401 Brazilian caves in limestone and iron-rich rocks was analysed statistically to infer the relative frequency of each criterion in assigning significance to caves. The analysis included 70 parameters; 30 were present in caves, but on average less than five of these parameters occurred together at each cave. Subjective parameters tended to be less represented. Biotic parameters were dominant and both abiotic and biotic parameters displayed a correlation with length and area, suggesting that these parameters could be good indicators of cave significance. Applying the set of criteria proposed by the Brazilian government to our sample, there was no marked difference between caves in different rock types. A better approach to defining cave relevance is required, with an emphasis on science-based parameters.
Which Is the Fairest (Rent Division) of Them All?
Authors: Gal Ya’akov (Kobi) , Mash Moshe , Procaccia Ariel D. , Zick Yair
Published: November 2017

“Mirror, mirror, on the wall, who is the fairest of them all?”

The Evil Queen

What is a
fair
way to assign rooms to several housemates and divide the rent between them? This is not just a theoretical question: many people have used the
Spliddit
website to obtain
envy-free
solutions to rent division instances. But envy freeness, in and of itself, is insufficient to guarantee outcomes that people view as intuitive and acceptable. We therefore focus on solutions that optimize a criterion of social justice, subject to the envy-freeness constraint, in order to pinpoint the “fairest” solutions. We develop a general algorithmic framework that enables the computation of such solutions in polynomial time. We then study the relations between natural optimization objectives and identify the
maximin
solution, which maximizes the minimum utility subject to envy freeness, as the most attractive. We demonstrate, in theory and using experiments on real data from Spliddit, that the maximin solution gives rise to significant gains in terms of our optimization objectives. Finally, a user study with Spliddit users as subjects demonstrates that people find the maximin solution to be significantly fairer than arbitrary envy-free solutions; this user study is unprecedented in that it asks people about their real-world rent division instances. Based on these results, the maximin solution has been deployed on Spliddit since April 2015.
Foxo1 nucleo-cytoplasmic distribution and unidirectional nuclear influx are the same in nuclei in a single skeletal muscle fiber but vary between fibers
Authors: Liu Yewei , Russell Sarah J. , Schneider Martin F.
Published: November 2017

Foxo transcription factors promote protein breakdown and atrophy of skeletal muscle fibers. Foxo transcriptional effectiveness is largely determined by phosphorylation-dependent nucleo-cytoplasmic shuttling. Imaging Foxo1-green fluorescent protein (GFP) over time in 124 nuclei in 68 multinucleated adult skeletal muscle fibers under control culture conditions reveals large variability between fibers in Foxo1-GFP nucleo-cytoplasmic concentration ratio (N/C) and in the apparent rate coefficient ( kI′) for Foxo1-GFP unidirectional nuclear influx (measured with efflux blocked by leptomycin B). Pairs of values of N/C or of kI′ from different nuclei in the same fiber were essentially the same, but only weakly correlated in nuclei from different fibers in the same culture well. Thus, fiber to fiber variability of cellular factors, but not extracellular factors, determines Foxo1 distribution. Over all nuclei, N/C and kI′ were closely proportional, indicating that kI′ is the major determinant of Foxo1 distribution. IGF-I activation of Foxo kinase Akt reduces variability by decreasing kI′ and N/C in all fibers. However, inhibiting Akt did not drive kI′ uniformly high, indicating other pathways in Foxo1 regulation.
Electrical pulse stimulation induces GLUT4 translocation in C2C12myotubes that depends on Rab8A, Rab13, and Rab14
Authors: Li Zhu , Yue Yingying , Hu Fang , Zhang Chang , Ma Xiaofang , Li Nana , Qiu Lihong , Fu Maolong , Chen Liming , Yao Zhi , Bilan Philip J. , Klip Amira , Niu Wenyan
Published: November 2017

The signals mobilizing GLUT4 to the plasma membrane in response to muscle contraction are less known than those elicited by insulin. This disparity is undoubtedly due to lack of suitable in vitro models to study skeletal muscle contraction. We generated C2C12myotubes stably expressing HA-tagged GLUT4 (C2C12-GLUT4 HA) that contract in response to electrical pulse stimulation (EPS) and investigated molecular mechanisms regulating GLUT4 HA. EPS (60 min, 20 V, 1 Hz, 24-ms pulses at 976-ms intervals) elicited a gain in surface GLUT4 HA (GLUT4 translocation) comparably to insulin or 5-amino imidazole-4-carboxamide ribonucleotide (AICAR). A myosin II inhibitor prevented EPS-stimulated myotube contraction and reduced surface GLUT4 by 56%. EPS stimulated AMPK and CaMKII phosphorylation, and EPS-stimulated GLUT4 translocation was reduced in part by small interfering (si)RNA-mediated AMPKα1/α2 knockdown, compound C, siRNA-mediated Ca2+/calmodulin-dependent protein kinase (CaMKII)δ knockdown, or CaMKII inhibitor KN93. Key regulatory residues on the Rab-GAPs AS160 and TBC1D1 were phosphorylated in response to EPS. Stable expression of an activated form of the Rab-GAP AS160 (AS160-4A) diminished EPS- and insulin-stimulated GLUT4 translocation, suggesting regulation of GLUT4 vesicle traffic by Rab GTPases. Knockdown of each Rab8a, Rab13, or Rab14 reduced, in part, GLUT4 translocation induced by EPS, whereas only Rab8a, or Rab14 knockdown reduced the AICAR response. In conclusion, EPS involves Rab8a, Rab13, and Rab14 to elicit GLUT4 translocation but not Rab10; moreover, Rab10 and Rab13 are not engaged by AMPK activation alone. C2C12-GLUT4 HA cultures constitute a valuable in vitro model to investigate molecular mechanisms of contraction-stimulated GLUT4 translocation.
Exercise training reduces intrahepatic lipid content in people with and people without nonalcoholic fatty liver
Authors: Brouwers Bram , Schrauwen-Hinderling Vera B. , Jelenik Tomas , Gemmink Anne , Sparks Lauren M. , Havekes Bas , Bruls Yvonne , Dahlmans Dennis , Roden Michael , Hesselink Matthijs K.C. , Schrauwen Patrick
Published: November 2017

Exercise training reduces intrahepatic lipid (IHL) content in people with elevated liver fat content. It is unclear, however, whether exercise training reduces IHL content in people with normal liver fat content. Here, we measured the effect of exercise training on IHL content in people with and people without nonalcohol fatty liver. We further measured changes in insulin sensitivity and hepatic energy metabolism. Eleven males with nonalcoholic fatty liver (NAFL) and 11 body mass index-matched individuals without nonalcoholic fatty liver (CON) completed a 12-wk supervised exercise training program. IHL content (proton magnetic resonance spectroscopy), maximal oxidative capacity (V̇o2max, spiroergometry), total muscle strength, body composition, insulin sensitivity (hyperinsulinemic-euglycemic clamp), hepatic ATP-to-total phosphorus ratio, and the hepatic phosphomonoester-to-phosphodiester (PME/PDE) ratio (phosphorus magnetic resonance spectroscopy) were determined. IHL content reduced with exercise training ( P = 0.014) in the whole study population. The relative reduction in IHL content was comparable in NAFL (−34.5 ± 54.0%) and CON (−28.3 ± 60.1%) individuals ( P = 0.800). V̇o2max ( P < 0.001), total muscle strength ( P < 0.001), and skeletal muscle insulin sensitivity ( P = 0.004) increased, whereas adipose tissue ( P = 0.246) and hepatic ( P = 0.086) insulin sensitivity did not increase significantly. Hepatic ATP-to-total phosphorus ratio ( P = 0.987) and PME/PDE ratio ( P = 0.792) did not change. Changes in IHL content correlated with changes in body weight ( r = 0.451, P = 0.035) and changes in hepatic PME/PDE ratio ( r = 0.569, P = 0.019). In conclusion, exercise training reduced intrahepatic lipid content in people with nonalcoholic fatty liver and in people with normal intrahepatic lipid content, and the percent reduction in intrahepatic lipid content was similar in both groups.
Modeling insulin resistance in rodents by alterations in diet: what have high-fat and high-calorie diets revealed?
Authors: Small Lewin , Brandon Amanda E. , Turner Nigel , Cooney Gregory J.
Published: November 2017

For over half a century, researchers have been feeding different diets to rodents to examine the effects of macronutrients on whole body and tissue insulin action. During this period, the number of different diets and the source of macronutrients employed have grown dramatically. Because of the large heterogeneity in both the source and percentage of different macronutrients used for studies, it is not surprising that different high-calorie diets do not produce the same changes in insulin action. Despite this, diverse high-calorie diets continue to be employed in an attempt to generate a “generic” insulin resistance. The high-fat diet in particular varies greatly between studies with regard to the source, complexity, and ratio of dietary fat, carbohydrate, and protein. This review examines the range of rodent dietary models and methods for assessing insulin action. In almost all studies reviewed, rodents fed diets that had more than 45% of dietary energy as fat or simple carbohydrates had reduced whole body insulin action compared with chow. However, different high-calorie diets produced significantly different effects in liver, muscle, and whole body insulin action when insulin action was measured by the hyperinsulinemic-euglycemic clamp method. Rodent dietary models remain an important tool for exploring potential mechanisms of insulin resistance, but more attention needs to be given to the total macronutrient content and composition when interpreting dietary effects on insulin action.
N-linked glycans are required on epithelial Na+channel subunits for maturation and surface expression
Authors: Kashlan Ossama B. , Kinlough Carol L. , Myerburg Michael M. , Shi Shujie , Chen Jingxin , Blobner Brandon M. , Buck Teresa M. , Brodsky Jeffrey L. , Hughey Rebecca P. , Kleyman Thomas R.
Published: November 2017

Epithelial Na+channel (ENaC) subunits undergo N-linked glycosylation in the endoplasmic reticulum where they assemble into an αβγ complex. Six, 13, and 5 consensus sites (Asn-X-Ser/Thr) for N-glycosylation reside in the extracellular domains of the mouse α-, β-, and γ-subunits, respectively. Because the importance of ENaC N-linked glycans has not been fully addressed, we examined the effect of preventing N-glycosylation of specific subunits on channel function, expression, maturation, and folding. Heterologous expression in Xenopus oocytes or Fischer rat thyroid cells with αβγ-ENaC lacking N-linked glycans on a single subunit reduced ENaC activity as well as the inhibitory response to extracellular Na+. The lack of N-linked glycans on the β-subunit also precluded channel activation by trypsin. However, channel activation by shear stress was N-linked glycan independent, regardless of which subunit was modified. We also discovered that the lack of N-linked glycans on any one subunit reduced the total and surface levels of cognate subunits. The lack of N-linked glycans on the β-subunit had the largest effect on total levels, with the lack of N-linked glycans on the γ- and α-subunits having intermediate and modest effects, respectively. Finally, channels with wild-type β-subunits were more sensitive to limited trypsin proteolysis than channels lacking N-linked glycans on the β-subunit. Our results indicate that N-linked glycans on each subunit are required for proper folding, maturation, surface expression, and function of the channel.
Ste20-like kinase, SLK, a novel mediator of podocyte integrity
Authors: Cybulsky Andrey V. , Papillon Joan , Guillemette Julie , Belkina Natalya , Patino-Lopez Genaro , Torban Elena
Published: November 2017

SLK is essential for embryonic development and may play a key role in wound healing, tumor growth, and metastasis. Expression and activation of SLK are increased in kidney development and during recovery from ischemic acute kidney injury. Overexpression of SLK in glomerular epithelial cells/podocytes in vivo induces injury and proteinuria. Conversely, reduced SLK expression leads to abnormalities in cell adhesion, spreading, and motility. Tight regulation of SLK expression thus may be critical for normal renal structure and function. We produced podocyte-specific SLK-knockout mice to address the functional role of SLK in podocytes. Mice with podocyte-specific deletion of SLK showed reduced glomerular SLK expression and activity compared with control. Podocyte-specific deletion of SLK resulted in albuminuria at 4–5 mo of age in male mice and 8–9 mo in female mice, which persisted for up to 13 mo. At 11–12 mo, knockout mice showed ultrastructural changes, including focal foot process effacement and microvillous transformation of podocyte plasma membranes. Mean foot process width was approximately twofold greater in knockout mice compared with control. Podocyte number was reduced by 35% in knockout mice compared with control, and expression of nephrin, synaptopodin, and podocalyxin was reduced in knockout mice by 20–30%. In summary, podocyte-specific deletion of SLK leads to albuminuria, loss of podocytes, and morphological evidence of podocyte injury. Thus, SLK is essential to the maintenance of podocyte integrity as mice age.
Renal tubular ACE-mediated tubular injury is the major contributor to microalbuminuria in early diabetic nephropathy
Authors: Eriguchi Masahiro , Lin Mercury , Yamashita Michifumi , Zhao Tuantuan V. , Khan Zakir , Bernstein Ellen A. , Gurley Susan B. , Gonzalez-Villalobos Romer A. , Bernstein Kenneth E. , Giani Jorge F.
Published: November 2017

Diabetic nephropathy is a major cause of end-stage renal disease in developed countries. While angiotensin-converting enzyme (ACE) inhibitors are used to treat diabetic nephropathy, how intrarenal ACE contributes to diabetic renal injury is uncertain. Here, two mouse models with different patterns of renal ACE expression were studied to determine the specific contribution of tubular vs. glomerular ACE to early diabetic nephropathy: it-ACE mice, which make endothelial ACE but lack ACE expression by renal tubular epithelium, and ACE 3/9 mice, which lack endothelial ACE and only express renal ACE in tubular epithelial cells. The absence of endothelial ACE normalized the glomerular filtration rate and endothelial injury in diabetic ACE 3/9 mice. However, these mice developed tubular injury and albuminuria and displayed low renal levels of megalin that were similar to those observed in diabetic wild-type mice. In diabetic it-ACE mice, despite hyperfiltration, the absence of renal tubular ACE greatly reduced tubulointerstitial injury and albuminuria and increased renal megalin expression compared with diabetic wild-type and diabetic ACE 3/9 mice. These findings demonstrate that endothelial ACE is a central regulator of the glomerular filtration rate while tubular ACE is a key player in the development of tubular injury and albuminuria. These data suggest that tubular injury, rather than hyperfiltration, is the main cause of microalbuminuria in early diabetic nephropathy.
Klotho and activin A in kidney injury: plasma Klotho is maintained in unilateral obstruction despite no upregulation of Klotho biosynthesis in the contralateral kidney
Authors: Nordholm Anders , Mace Maria L. , Gravesen Eva , Hofman-Bang Jacob , Morevati Marya , Olgaard Klaus , Lewin Ewa
Published: November 2017

In a new paradigm of etiology related to chronic kidney disease-mineral and bone disorder (CKD-MBD), kidney injury may cause induction of factors in the injured kidney that are released into the circulation and thereby initiate and maintain renal fibrosis and CKD-MBD. Klotho is believed to ameliorate renal fibrosis and CKD-MBD, while activin A might have detrimental effects. The unilateral ureter obstruction (UUO) model is used here to examine this concept by investigating early changes related to renal fibrosis in the obstructed kidney, untouched contralateral kidney, and vasculature which might be affected by secreted factors from the obstructed kidney, and comparing with unilateral nephrectomized controls (UNX). Obstructed kidneys showed early Klotho gene and protein depletion, whereas plasma Klotho increased in both UUO and UNX rats, indicating an altered metabolism of Klotho. Contralateral kidneys had no compensatory upregulation of Klotho and maintained normal expression of the examined fibrosis-related genes, as did remnant UNX kidneys. UUO caused upregulation of transforming growth factor-β and induction of periostin and activin A in obstructed kidneys without changes in the contralateral kidneys. Plasma activin A doubled in UUO rats after 10 days while no changes were seen in UNX rats, suggesting secretion of activin A from the obstructed kidney with potentially systemic effects on CKD-MBD. As such, increased aortic sclerostin was observed in UUO rats compared with UNX and normal controls. The present results are in line with the new paradigm and show very early vascular effects of unilateral kidney fibrosis, supporting the existence of a new kidney-vasculature axis.
Quantitative relations between BOLD responses, cortical energetics, and impulse firing
Authors: Bennett M. R. , Farnell L. , Gibson W. G.
Published: November 2017

The blood oxygen level-dependent (BOLD) functional magnetic resonance imaging signal arises as a consequence of changes in blood flow and oxygen usage that in turn are modulated by changes in neural activity. Much attention has been given to both theoretical and experimental aspects of the energetics but not to the neural activity. Here we identify the best energetic theory for the steady-state BOLD signal on the basis of correct predictions of experimental observations. This theory is then used, together with the recently determined relationship between energetics and neural activity, to predict how the BOLD signal changes with activity. Unlike existing treatments, this new theory incorporates a nonzero baseline activity in a completely consistent way and is thus able to account for both sustained positive and negative BOLD signals. We also show that the increase in BOLD signal for a given increase in activity is significantly smaller the larger the baseline activity, as is experimentally observed. Furthermore, the decline of the positive BOLD signal arising from deeper cortical laminae in response to an increase in neural firing is shown to arise as a consequence of the larger baseline activity in deeper laminae. Finally, we provide quantitative relations integrating BOLD responses, energetics, and impulse firing, which among other predictions give the same results as existing theories when the baseline activity is zero.

NEW & NOTEWORTHY We use a recently established relation between energetics and neural activity to give a quantitative account of BOLD dependence on neural activity. The incorporation of a nonzero baseline neural activity accounts for positive and negative BOLD signals, shows that changes in neural activity give BOLD changes that are smaller the larger the baseline, and provides a basis for the observed inverse relation between BOLD responses and the depth of cortical laminae giving rise to them.
Ih interacts with somato-dendritic structure to determine frequency response to weak alternating electric field stimulation
Authors: Toloza Enrique H. S. , Negahbani Ehsan , Fröhlich Flavio
Published: November 2017

Transcranial current stimulation (tCS) modulates brain dynamics using weak electric fields. Given the pathological changes in brain network oscillations in neurological and psychiatric illnesses, using alternating electric field waveforms that engage rhythmic activity has been proposed as a targeted, network-level treatment approach. Previous studies have investigated the effects of electric fields at the neuronal level. However, the biophysical basis of the cellular response to electric fields has remained limited. Here, we characterized the frequency-dependent response of different compartments in a layer V pyramidal neuron to exogenous electric fields to dissect the relative contributions of voltage-gated ion channels and neuronal morphology. Hyperpolarization-activated cation current (Ih) in the distal dendrites was the primary ionic mechanism shaping the model’s response to electric field stimulation and caused subthreshold resonance in the tuft at 20 ± 4 Hz. In contrast, subthreshold Ih-mediated resonance in response to local sinusoidal current injection was present in all model compartments at 11 ± 2 Hz. The frequencies of both resonance responses were modulated by Ih conductance density. We found that the difference in resonance frequency between the two stimulation types can be explained by the fact that exogenous electric fields simultaneously polarize the membrane potentials at the distal ends of the neuron (relative to field direction) in opposite directions. Our results highlight the role of Ih in shaping the cellular response to electric field stimulation and suggest that the common model of tCS as a weak somatic current injection fails to capture the cellular effects of electric field stimulation.

NEW & NOTEWORTHY Modulation of cortical oscillation by brain stimulation serves as a tool to understand the causal role of network oscillations in behavior and is a potential treatment modality that engages impaired network oscillations in disorders of the central nervous system. To develop targeted stimulation paradigms, cellular-level effects must be understood. We demonstrate that hyperpolarization-activated cation current (Ih) and cell morphology cooperatively shape the response to applied alternating electric fields.
Time course of functional recovery during the first 3 mo after surgical transection and repair of nerves to the feline soleus and lateral gastrocnemius muscles
Authors: Gregor Robert J. , Maas Huub , Bulgakova Margarita A. , Oliver Alanna , English Arthur W. , Prilutsky Boris I.
Published: November 2017

Locomotion outcomes after peripheral nerve injury and repair in cats have been described in the literature for the period immediately following the injury (muscle denervation period) and then again for an ensuing period of long-term recovery (at 3 mo and longer) resulting in muscle self-reinnervation. Little is known about the changes in muscle activity and walking mechanics during midrecovery, i.e., the early reinnervation period that takes place between 5 and 10 wk of recovery. Here, we investigated hindlimb mechanics and electromyogram (EMG) activity of ankle extensors in six cats during level and slope walking before and every 2 wk thereafter in a 14-wk period of recovery after the soleus (SO) and lateral gastrocnemius (LG) muscle nerves in one hindlimb were surgically transected and repaired. We found that the continued increase in SO and LG EMG magnitudes and corresponding changes in hindlimb mechanics coincided with the formation of neuromuscular synapses revealed in muscle biopsies. Throughout the recovery period, EMG magnitude of SO and LG during the stance phase and the duration of the stance-related activity were load dependent, similar to those in the intact synergistic medial gastrocnemius and plantaris. These results and the fact that EMG activity of ankle extensors and locomotor mechanics during level and upslope walking recovered 14 wk after nerve transection and repair suggest that loss of the stretch reflex in self-reinnervated muscles may be compensated by the recovered force-dependent feedback in self-reinnervated muscles, by increased central drive, and by increased gain in intermuscular motion-dependent pathways from intact ankle extensors.

NEW & NOTEWORTHY This study provides new evidence that the timeline for functional recovery of gait after peripheral nerve injury and repair is consistent with the time required for neuromuscular junctions to form and muscles to reach preoperative tensions. Our findings suggest that a permanent loss of autogenic stretch reflex in self-reinnervated muscles may be compensated by recovered intermuscular force-dependent and oligosynaptic length-dependent feedback and central drive to regain adequate locomotor output capabilities during level and upslope walking.
The assessment of neurovascular coupling with the Addenbrooke’s Cognitive Examination: a functional transcranial Doppler ultrasonographic study
Authors: Beishon Lucy C. , Williams Claire A. L. , Panerai Ronney B. , Robinson Thompson G. , Haunton Victoria J.
Published: November 2017

Cerebrovascular dysfunction occurs early in dementia and can be identified by transcranial Doppler ultrasonography (TCD). Few studies have examined cerebral blood flow velocity (CBFv) responses to a detailed cognitive battery. This study aimed to characterize all CBFv responses, and the effect of hemispheric dominance, to the Addenbrooke’s Cognitive Examination (ACE-III) in healthy volunteers. Forty volunteers underwent continuous bilateral TCD, beat-to-beat blood pressure (MAP; Finapres), heart rate (HR; electrocardiogram), and end-tidal CO2 (ETCO2; capnography) monitoring. After a 5-min baseline period, all tasks from the ACE-III were performed in 3 sections (A: attention, fluency, memory; B: language; C: visuospatial, memory). Data are population mean normalized percentage (PM%) change from a 20-s baseline period before task initiation. Forty bilateral data sets were obtained (27 women, 37 right-hand dominant). All paradigms produced a sharp increase in CBFv in both dominant (PM% range: 3.29 to 9.70%) and nondominant (PM% range: 4.34 to 11.63%) hemispheres at task initiation, with associated increases in MAP (PM% range: 3.06 to 16.04%). ETCO2 did not differ significantly at task initiation (PM% range: −1.1 to 2.4%, P > 0.05). HR differed significantly across A and C tasks at initiation (PM% range: −1.1 to 2.4%, P < 0.05), but not B tasks. In conclusion, all tasks resulted in increases in CBFv, differing significantly between paradigms. These results require further investigation in a cognitively impaired population.

NEW & NOTEWORTHY This study is the first to provide a normative data set of cerebral blood flow velocity (CBFv) responses to a complete cognitive assessment (Addenbrooke’s Cognitive Examination, ACE-III) in a large sample ( n = 40) of healthy volunteers. All tasks produced peak and sustained increases in CBFv to different extents. The ACE-III is a feasible tool to assess neurovascular coupling with transcranial Doppler ultrasonography. These data can be used to inform the most appropriate cognitive task to elicit CBFv responses for future studies.