bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating the effective number of breeders from single parr samples for conservation monitoring of wild populations of Atlantic salmon Salmo salar
Authors: Bacles C. F. E. , Bouchard C. , Lange F. , Manicki A. , Tentelier C. , Lepais O.
Published: January 2018

This study assesses whether the effective number of breeders (Nb) can be estimated using a time and cost‐effective protocol using genetic sibship reconstruction from a single sample of young‐of‐the‐year (YOY) for the purposes of Atlantic salmon Salmo salar population monitoring. Nb was estimated for 10 consecutive reproductive seasons for S. salar in the River Nivelle, a small population located at the rear‐edge of the species distribution area in France, chronically under its conservation limit and subjected to anthropogenic and environmental changes. Subsampling of real and simulated data showed that accurate estimates of Nb can be obtained from YOY genotypes, collected at moderate random sampling intensity, achievable using routine juvenile electrofishing protocols. Spatial bias and time elapsed since spawning were found to affect estimates, which must be accounted for in sampling designs. Nb estimated in autumn for S. salar in the River Nivelle was low and variable across years from 23 (95% C.I. 14–41) to 75 (53–101) and was not statistically correlated with the estimated number of returning adults, but it was positively correlated with the estimated number of YOY at age 9 months. Nb was found to be lower for intermediate levels of redd aggregation, suggesting that the strength of the competition between males to access females affects reproductive success variance depending on redd spatial configuration. Thus, environmental factors such as habitat availability and quality for spawning and YOY development predominate over demographic ones (number of returning adults) in driving long‐term population viability for S. salar in the River Nivelle. This study showcases Nb as an integrated parameter, encompassing demographic and ecological information about a reproductive event, relevant to the assessment of both short‐term effects of management practices and long‐term population conservation status.
Watch‐and‐wait policy versus rituximab‐combined chemotherapy in Japanese patients with intestinal follicular lymphoma
Authors: Tari Akira , Kitadai Yasuhiko , Mouri Ritsuo , Takigawa Hidehiko , Asaoku Hideki , Mihara Keiichiro , Takata Katsuyoshi , Fujihara Megumu , Yoshino Tadashi , Koga Tadashi , Fujimori Shunji , Tanaka Shinji , Chayama Kazuaki
Published: January 2018

Background and Aim

Few reports have demonstrated the effectiveness of treatments for intestinal follicular lymphoma (FL) because of the limited number of patients who undergo comprehensive small intestinal examinations. This study compared the efficacy of rituximab‐combined chemotherapy in patients with asymptomatic and low tumor burden (LTB) intestinal FL, according to the criteria of the Groupe d'Etude des Lymphomes Folliculaires, with that of a “watch and wait” (W&W) approach.

Methods

The endoscopic examination for entire gastrointestinal tracts was performed in 29 Japanese patients with intestinal FL. These patients had CD21‐positive follicular dendritic cells arranged in a duodenal pattern. In a prospective, two‐center, open‐label trial, this study evaluated the efficacy of rituximab‐combined chemotherapy ([cyclophosphamide, doxorubicin, vincristine, and prednisone] or [cyclophosphamide, vincristine, and prednisone]) and prolonged treatment with rituximab (R‐Chemo+prolongedR) in 14 patients and compared their outcomes with those of 15 patients managed with a W&W approach.

Results

Four patients managed with the W&W plan showed worsening macroscopic findings, lesion area enlargement, or clinical stage progression but stayed on this plan because they had LTB and experienced no changes in bowel function. In the R‐Chemo+prolongedR group, all patients achieved complete remission; recurrence occurred in one patient, who was subsequently managed with the W&W plan because of LTB. There were no significant differences in progression‐free survival between the two groups (P = 0.1045). Overall survival was 100% in both groups.

Conclusions

The prognoses of patients with asymptomatic intestinal FL and LTB who were managed with a W&W strategy were comparable with those of patients receiving R‐Chemo+prolongedR.
Autosomal recessive congenital cataract in captive‐bred vervet monkeys (Chlorocebus aethiops)
Authors: Magwebu Zandisiwe E. , Abdul‐Rasool Sahar , Seier Jürgen V. , Chauke Chesa G.
Published: January 2018

Background

The aim of the study was to evaluate the genetic predisposition of congenital cataract in a colony of captive‐bred vervet monkeys.

Methods

Four congenital cataract genes: glucosaminyl (N‐acetyl) transferase 2 (GCNT2), heat shock transcription factor 4 (HSF4), crystallin alpha A (CRYAA) and lens intrinsic membrane protein‐2 (LIM2) were screened, sequenced and analysed for possible genetic variants in 36 monkeys. Gene expression was also evaluated in these genes.

Results

Fifteen sequence variants were identified in the coding regions of three genes (GCNT2, HSF4 and CRYAA). Of these variations, only three were missense mutations (M258V, V16I and S24N) and identified in the GCNT2 transcripts A, B and C, respectively, which resulted in a downregulated gene expression.

Conclusion

Although the three missense mutations in GCNT2 have a benign effect, a possibility exists that the candidate genes (GCNT2, HSF4 and CRYAA) might harbour mutations that are responsible for total congenital cataract.
Subsequent Unintended Pregnancy Among US Women Who Receive or Are Denied a Wanted Abortion
Authors: Aztlan Evelyn Angel , Foster Diana Greene , Upadhyay Ushma
Published: January 2018

Introduction

Seventeen percent of women in the United States experience more than one unintended pregnancy in their lifetimes. However, few studies examine how the resolution of unintended pregnancy, whether in birth or abortion, affects the likelihood of a subsequent unintended pregnancy. Our objective was to determine whether receiving or being denied a wanted abortion is associated with subsequent unintended pregnancy.

Methods

The Turnaway Study, a 5‐year, prospective cohort study, followed women who sought an abortion at one of 30 abortion facilities across the United States between 2008 and 2010. Secondary analysis of the Turnaway data analyzed the effects of various factors on time to subsequent unintended pregnancy.

Results

By 5 years, the rate of unintended pregnancy was 42 per 100 women with no difference between those who received and those who were denied a wanted abortion. Women aged 35 to 46 years (vs those aged 20‐24 years), women with a college degree (vs women who had completed high school or obtained a general education diploma), and foreign‐born (vs native‐born) women had a reduced rate of a subsequent unplanned pregnancy (adjusted hazard ratio [AHR], 0.30; 95% confidence interval [CI], 0.16‐0.57; AHR, 0.54, 95% CI, 0.30‐0.97; AHR, 0.44; 95% CI, 0.25‐0.77, respectively). Higher parity and a history of depression were positively associated with a higher rate of subsequent unintended pregnancy. There was no difference in the outcomes of these unintended pregnancies by study group; approximately one‐sixth ended in miscarriage and one‐quarter of subsequent unintended pregnancies ended in abortion.

Discussion

Neither receiving nor being denied abortion is associated with subsequent unintended pregnancy risk. Other factors such as nativity, parity, age, and mental health history are associated with multiple unintended pregnancies. Ensuring access to abortion services will not increase the likelihood that women will experience subsequent unintended pregnancies.
Purinergic signaling in oligodendrocyte development and function
Authors: Welsh Taylor G. , Kucenas Sarah
Published: January 2018

Myelin, an insulating membrane that enables rapid action potential propagation, is an essential component of an efficient, functional vertebrate nervous system. Oligodendrocytes, the myelinating glia of the central nervous system (CNS), produce myelin throughout the CNS, which requires continuous proliferation, migration, and differentiation of oligodendrocyte progenitor cells. Because myelination is essential for efficient neurotransmission, researchers hypothesize that neuronal signals may regulate the cascade of events necessary for this process. The ability of oligodendrocytes and oligodendrocyte progenitor cells to detect and respond to neuronal activity is becoming increasingly appreciated, although the specific signals involved are still a matter of debate. Recent evidence from multiple studies points to purinergic signaling as a potential regulator of oligodendrocyte development and differentiation. Adenosine triphosphate (ATP) and its derivatives are potent signaling ligands with receptors expressed on many populations of cells in the nervous system, including cells of the oligodendrocyte lineage. Release of ATP into the extracellular space can initiate a multitude of signaling events, and these downstream signals are specific to the particular purinergic receptor (or receptors) expressed, and whether enzymes are present to hydrolyze ATP to its derivatives adenosine diphosphate and adenosine, each of which can activate their own unique downstream signaling cascades. This review will introduce purinergic signaling in the CNS and discuss evidence for its effects on oligodendrocyte proliferation, differentiation, and myelination. We will review sources of extracellular purines in the nervous system and how changes in purinergic receptor expression may be coupled to oligodendrocyte differentiation. We will also briefly discuss purinergic signaling in injury and diseases of the CNS.

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I Know, but I Would Rather Be Beautiful: The Impact of Self‐Esteem, Narcissism, and Knowledge on Addictive Tanning Behavior in Millennials
Authors: Watson Amy , Zank Gail , Turri Anna M.
Published: January 2018

This research examines consumers' current level of sun protection knowledge and prevention, tanning motivation, and behavior. This baseline information provides a clearer understanding of actual consumer behavior and can be used to determine what knowledge deficits exist so that future research, educational materials, and communication efforts can be tailored to address those more directly. Additionally, the relationships between knowledge, self‐esteem, and narcissism are explored. Results show that knowledge has no impact on addictive tanning behavior, self‐esteem is negatively correlated, and narcissism is fully mediated by appearance motivation. Implications, potential regulatory, and communication efforts are discussed.
A Systematic Literature Review to Identify Successful Elements for Financial Education and Counseling in Groups
Authors: Peeters Nele , Rijk Kathinka , Soetens Barbara , Storms Bérénice , Hermans Koen
Published: January 2018

This study reviews the literature available on contents, form, and effectiveness of group‐based programs for combined financial education and counseling aimed specifically at populations at risk for financial difficulties. Despite the widespread application of these programs, relatively little is known about their effectiveness. In general, evidence points to positive effects of several programs on knowledge, confidence, and (intended) behavior, but the exact mechanisms through which this is achieved remain unclear. The topics covered differ among studies, but common themes can be identified. It appears of importance to combine education with practical exercises allowing participants to apply the skills they learn. Motivating clients is another important recurring theme. Working in groups provides an added benefit through recognition and peer support. It is important that future research focuses on the mechanisms of change and on long‐term effects, since these remain largely unknown in the current body of literature.
Conditional Families and Lesbian, Gay, Bisexual, Transgender, and Queer Youth Homelessness: Gender, Sexuality, Family Instability, and Rejection
Authors: Robinson Brandon Andrew
Published: January 2018

Existing research on lesbian, gay, bisexual, transgender, and queer (LGBTQ) youth homelessness identifies family rejection as a main pathway into homelessness for the youth. This finding, however, can depict people of color or poor people as more prejudiced than White, middle‐class families. In this 18‐month ethnographic study, the author complicates this rejection paradigm through documenting the narratives of 40 LGBTQ youth experiencing homelessness. The author examines how poverty and family instability shaped the conditions that the youth perceived as their being rejected because of their gender and sexuality. This rejection generated strained familial ties within families wherein the ties were already fragile. Likewise, the author shows how being gender expansive marked many youth's experiences of familial abuse and strain. This study proposes the concept of conditional families to capture the social processes of how poverty and family instability shape experiences of gender, sexuality, and rejection for some LGBTQ youth.
Echocardiographic Evaluation of the Right Atrial Area Index in Dogs with Pulmonary Hypertension
Authors: Vezzosi T. , Domenech O. , Iacona M. , Marchesotti F. , Zini E. , Venco L. , Tognetti R.
Published: January 2018

Background

Right atrial area (RAA) is a prognostic factor in human patients with pulmonary arterial hypertension (PAH). Reference intervals for RAA have been described in healthy dogs.

Objectives

To evaluate RAA indexed to the body surface area in dogs with PAH as an indicator of right atrial size, PAH severity and right‐sided congestive heart failure (R‐CHF).

Animals

A total of 119 client‐owned dogs, 48 dogs with PAH and 71 control dogs.

Methods

Prospective observational study. Pulmonary arterial hypertension was classified according to the tricuspid regurgitation pressure gradient (TRPG) as mild (36–50 mmHg), moderate (51–75 mmHg), or severe (>75 mmHg). The RAA index was calculated as the RAA divided by body surface area.

Results

The RAA index was higher in dogs with moderate PAH (13.3 cm2/m2; range, 3.4–24.7 cm2/m2) and severe PAH (12.1 cm2/m2; range, 5.4–21.8 cm2/m2) than in those with mild PAH (6.7 cm2/m2; range, 4.8–10.7 cm2/m2) or in controls (7.3 cm2/m2; range, 4.2–10.2 cm2/m2; P < 0.001). The RAA index was higher (P < 0.0001) in dogs with R‐CHF (17.5 cm2/m2; range, 12.7–24.7 cm2/m2) compared to those without R‐CHF (7.6 cm2/m2; range, 4.4–19.4 cm2/m2). The most accurate cutoff value of the RAA index to identify R‐CHF was >12.3 cm2/m2 (sensitivity, 100%; specificity, 89.5%). In dogs with PAH, severity of tricuspid regurgitation (TR) was the only independent predictor of RAA index based on multivariate analysis (P < 0.02).

Conclusions and Clinical Importance

The RAA index can be used to evaluate right atrial size in dogs and may be more effective than TRPG in predicting R‐CHF in dogs with PAH. The severity of TR is the main determinant of the RAA index in dogs with PAH.
Oral oxycodone/naloxone for pain control in cirrhosis: Start slow, go slow
Authors: Varela Maria , Castaño‐Garcia Andrés
Published: January 2018

See Article on Page 278
Improvement of hepatic fibrosis and patient‐reported outcomes in non‐alcoholic steatohepatitis treated with selonsertib
Authors: Younossi Zobair M. , Stepanova Maria , Lawitz Eric , Charlton Michael , Loomba Rohit , Myers Robert P. , Subramanian Mani , McHutchison John G. , Goodman Zachary
Published: January 2018

Background

Patient‐reported outcomes (PROs) represent patients’ perspective about their well‐being.

Aim

To assess PRO changes in patients with non‐alcoholic steatohepatitis (NASH) after treatment with selonsertib (SEL) and to associate them with different biomarkers.

Methods

Patients with NASH and stage 2‐3 fibrosis received SEL 6 mg or 18 mg orally QD alone or in combination with simtuzumab (SIM, 125 mg SC weekly) or SIM alone for 24 weeks. Biopsies were obtained at baseline and at treatment week 24. PROs were assessed using SF‐36, CLDQ and WPAI:SHP.

Results

Seventy‐two patients with NASH were included (54 ± 10 years, 31% male, 65% stage 3, 71% diabetes). Baseline physical health‐related PRO scores were significantly lower than population norms (P < .05). During treatment, there were no consistent differences in treatment‐emergent PRO changes between different regimens (P > .05). However, NASH subjects who experienced ≥2 decrease in NAFLD Activity Score or ≥1‐stage reduction in fibrosis showed significant improvements in their PROs (up to +15.5% of a PRO range size, P < .05). Additionally, improvements in PROs (up to +21.5%, P < .05) were noted in patients with at least 50% relative reduction in collagen, while NASH subjects with >17% increase in their collagen experienced PRO worsening (up to −13.9%, P < .05). Baseline serum CK‐18, IL‐6 and CRP significantly correlated with PROs (rho from −0.24 to −0.38, P < .05).

Conclusions

A decrease in hepatic collagen is the most prominently associated with improvement of PROs in NASH patients with F2‐F3 treated with SEL. Furthermore, serum cytokines are associated with baseline PROs and with treatment‐emergent changes in PROs in patients with NASH.
Ribavirin dose management in HCV patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin
Authors: Feld Jordan J. , Bernstein David E. , Younes Ziad , Vlierberghe Hans Van , Larsen Lois , Tatsch Fernando , Ferenci Peter
Published: January 2018

Background & Aims

Some individuals with hepatitis C virus infection treated with direct‐acting antivirals require ribavirin to maximize sustained virological response rates. We describe the clinical management of ribavirin dosing in hepatitis C virus‐infected patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin.

Methods

We performed a post hoc analysis of patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin for 12 or 24 weeks in six phase 3 trials. Multivariate stepwise logistic regression models assessed predictors associated with ribavirin dose adjustments and with developing anaemia.

Results

Of 1548 patients, 100 (6.5%) modified ribavirin dose due to haemoglobin declines, of which 99% achieved sustained virological response at 12 weeks post‐treatment. Median time to first ribavirin dose reduction was 37 days. Low baseline haemoglobin was significantly associated with an increased risk of requiring ribavirin dose modification (odds ratio: 0.618 [0.518, 0.738]; P < .001) and developing anaemia (odds ratio: 0.379 [0.243, 0.593]; P < .001).

Conclusions

Ribavirin dose reductions were infrequent, occurred early in treatment, and did not impact sustained virological response at 12 weeks post‐treatment. Patients with low baseline haemoglobin should be monitored for on‐treatment anaemia.
The semantics ofmany, much, few, andlittle
Authors: Rett Jessica
Published: January 2018

The wordsmany, much, few,andlittle(and their cross‐linguistic counterparts) are quite unusual semantically. They have traditionally been characterized as quantifiers (likeevery) or adjectives (liketall); however, these analyses can only account for instances of these terms in which they encode information about an individual or a set of individuals, as they do when they occur prenominally (in e.g.,much traffic). Recent degree‐semantic analyses instead characterize the meaning of these words in terms of intervals or sets of degrees; this accounts for their canonical uses and uses in which they don't appear to be ranging over individuals (as in their differential use, e.g.,much taller).
The Data Hustle: How Beneficiaries Benefit from Continual Data Collection and Humanitarian Aid Research in the Somali Region of Ethiopia
Authors: Carruth Lauren
Published: January 2018

Based on ethnographic and policy research in the Somali Region of Ethiopia, this article examines how contemporary trends in the humanitarian relief industry to mandate continual data collection, “accountability,” and the “localization” of aid have increased demands for participatory and intensive research methodologies in crisis‐affected communities. International humanitarian relief agencies hustle to hire local staffs and recruit enough participants for their repeated research projects, while at the same time, the so‐called beneficiaries of aid also hustle to participate in data collection as paid informants and temporary employees. Research is an important side gig for many beneficiaries, and beneficiaries’ regular participation is vital to reforming humanitarian practice. Beneficiaries are not therefore passive recipients of charity, but actively help produce the representations of crisis and suffering that, in turn, potentially qualify them for aid. Their indispensability and activity within contemporary humanitarian “audit cultures” therefore present emergent but limited forms of counter‐hegemonic power.
Salvinorin A ameliorates cerebral vasospasm through activation of endothelial nitric oxide synthase in a rat model of subarachnoid hemorrhage
Authors: Sun Juan , Zhang Yan , Lu Jianfei , Zhang Weiguang , Yan Junhao , Yang Lei , Zhou Changman , Liu Renyu , Chen Chunhua
Published: January 2018

Objective

This study aimed to demonstrate the potential of salvinorin A (SA) for cerebral vasospasm after subarachnoid hemorrhage (SAH) and investigate mechanisms of therapeutic effect using rat SAH model.

Methods

Salvinorin A was injected intraperitoneally, and the neurobehavioral changes were observed at 12 hours, 24 hours, 48 hours, and 72 hours after SAH. Basilar artery was observed by magnetic resonance imaging (MRI). The inner diameter and thickness of basilar artery were measured. The morphological changes and the apoptosis in CA1 area of hippocampus were detected. Endothelin‐1 (ET‐1) and nitric oxide (NO) levels were detected by ELISA kit. The protein expression of endothelial NO synthase (eNOS) and aquaporin‐4 (AQP‐4) was determined by Western blot for potential mechanism exploration.

Results

Salvinorin A administration could relieve neurological deficits, decrease the neuronal apoptosis, and alleviate the morphological changes in CA1 area of hippocampus. SA alleviated CVS by increasing diameter and decreasing thickness of basilar artery, and such changes were accompanied by the decreased concentration of ET‐1 and increased level of NO. Meanwhile, SA increased the expression of eNOS and decreased the expression of AQP‐4 protein in the basilar artery and hippocampus.

Conclusions

Salvinorin A attenuated CVS and alleviated brain injury after SAH via increasing expression of eNOS and NO content, and decreasing ET‐1 concentration and AQP‐4 protein expression.
Determination of Near‐Optimal Restoration Programs for Transportation Networks Following Natural Hazard Events Using Simulated Annealing
Authors: Hackl Jürgen , Adey Bryan T. , Lethanh Nam
Published: January 2018

Disruptive events, such as earthquakes, floods, and landslides, may disrupt the service provided by transportation networks on a vast scale, as their occurrence is likely to cause multiple objects to fail simultaneously. The restoration program following a disruptive event should restore service as much, and as fast, as possible. The estimation of risk due to natural hazards must take into consideration the resilience of the network, which requires estimating the restoration program as accurately as possible. In this article, a restoration model using simulated annealing is formulated to determine near‐optimal restoration programs following the occurrence of hazard events. The objective function of the model is to minimize the costs, taking into consideration the direct costs of executing the physical interventions, and the indirect costs that are being incurred due to the inadequate service being provided by the network. The constraints of the model are annual and total budget constraints, annual and total resource constraints, and the specification of the number and type of interventions to be executed within a given time period. The restoration model is demonstrated by using it to determine the near‐optimal restoration program for an example road network in Switzerland following the occurrence of an extreme flood event. The strengths and weaknesses of the restoration model are discussed, and an outlook for future work is given.
Nitrergic signaling via interstitial cells of Cajal and smooth muscle cells influences circular smooth muscle contractility in murine colon
Authors: Beck K. , Friebe A. , Voussen B.
Published: January 2018

Background

Regulation of gastrointestinal motility involves excitatory and inhibitory neurotransmission. Nitric oxide (NO), the major inhibitory neurotransmitter, acts via its receptor NO‐sensitive guanylyl cyclase (NO‐GC). In the GI tract, NO‐GC is expressed in several cell types such as smooth muscle cells (SMC) and interstitial cells of Cajal (ICC). Using cell‐specific knockout mice, we have previously shown that NO‐GC modulates spontaneous contractions in colonic longitudinal smooth muscle. However, its detailed role in the colonic circular smooth muscle is still unclear.

Methods

Myography was performed to evaluate spontaneous contractions in rings of proximal colon (2.5 mm) from global (GCKO) and cell‐specific knockout mice for NO‐GC. Immunohistochemistry and in situ hybridization were used to specify NO‐GC expression.

Key results

Colonic circular smooth muscle showed three different contraction patterns: high‐frequency ripples, slow phasic contractions, and large contractions. Ripples formed independently of NO‐GC. Slow phasic contractions occurred intermittently in WT, SMC‐GCKO, and ICC‐GCKO tissue, whereas they were more prominent and prolonged in GCKO and SMC/ICC‐GCKO tissue. Tetrodotoxin and the NO‐GC inhibitor ODQ transformed slow phasic contractions of WT and single cell‐specific knockout into GCKO‐like contractions. ODQ increased the frequency of large contractions in WT and ICC‐GCKO colon but not in GCKO, SMC‐GCKO, and SMC/ICC‐GCKO preparations. Tetrodotoxin and hexamethonium abolished large contractions.

Conclusions and Inferences

We conclude that short rings of murine colon can be effectively used to record spontaneous contractions. Although NO‐GC in SMC determines smooth muscle tone, concerted action of NO‐GC in both SMC and ICC modulates slow phasic contractions and large contractions.
Updates on obesity pharmacotherapy
Authors: Velazquez Amanda , Apovian Caroline M.
Published: January 2018

Obesity is a chronic, relapsing disease that necessitates a multidisciplinary approach to management. Behavioral changes are the foundation to management, but adjunctive therapy is often warranted, including pharmacologic therapies and/or bariatric surgery. Until recently, treatment options included only short‐term therapy (≤12 weeks), and paths beyond that schedule were challenging, as knowledge of the biology of obesity was lacking. With increased recognition of obesity as a chronic, complex medical disease, newer agents have been approved as long‐term therapy, and the cornerstone of treatment is chronic behavior and lifestyle change. In the last decade, the Food and Drug Administration (FDA) has approved several new weight loss medications for the chronic management of obesity. In this review paper, we provide the latest updates on obesity pharmacotherapy. The main areas we will cover include (1) pharmacological management of obesity, (2) a review of FDA‐approved weight loss medications, (3) comanagement of obesity and its metabolic sequelae (type 2 diabetes mellitus, hypertension, and dyslipidemia), and (4) obesity‐centric prescribing for mental illness, neurological disorders, and contraceptive planning.
Sulfur amino acid restriction–induced changes in redox‐sensitive proteins are associated with slow protein synthesis rates
Authors: Nichenametla Sailendra N. , Mattocks Dwight A.L. , Malloy Virginia L. , Pinto John T.
Published: January 2018

The mechanisms underlying life span extension by sulfur amino acid restriction (SAAR) are unclear. Cysteine and methionine are essential for the biosynthesis of proteins and glutathione (GSH), a major redox buffer in the endoplasmic reticulum (ER). We hypothesized that SAAR alters protein synthesis by modulating the redox milieu. Male F344‐rats were fed control (CD: 0.86% methionine without cysteine) and SAAR diets (0.17% methionine without cysteine) for 12 weeks. Growth rates, food intake, cysteine and GSH levels, proteins associated with redox status and translation, and fractional protein synthesis rates (FSRs) were determined in liver. Despite a 40% higher food intake, growth rates for SAAR rats were 27% of those fed CD. Hepatic free cysteine in SAAR rats was 55% compared with CD rats. SAAR altered tissue distribution of GSH, as hepatic and erythrocytic levels were 56% and 196% of those in CD rats. Lower GSH levels did not induce ER stress (i.e., unchanged expression of Xbp1s, Chop, and Grp78), but activated PERK and its substrates eIF2‐α and NRF2. SAAR‐induced changes in translation‐initiation machinery (higher p‐eIF2‐α and 4E‐BP1, and lower eIF4G‐1) resulted in slower protein synthesis rates (53% of CD). Proteins involved in the antioxidant response (NRF2, KEAP1, GCLM, and NQO1) and protein folding (PDI and ERO1‐α) were increased in SAAR. Lower FSR and efficient protein folding might be improving proteostasis in SAAR.
Cardioprotective effects of dietary rapamycin on adult female C57BLKS/J‐Leprdb mice
Authors: Reifsnyder Peter C. , Ryzhov Sergey , Flurkey Kevin , Anunciado‐Koza Rea P. , Mills Ian , Harrison David E. , Koza Robert A.
Published: January 2018

Rapamycin (RAPA), an inhibitor of mTORC signaling, has been shown to extend life span in mice and other organisms. Recently, animal and human studies have suggested that inhibition of mTORC signaling can alleviate or prevent the development of cardiomyopathy. In view of this, we used a murine model of type 2 diabetes (T2D), BKS‐Leprdb, to determine whether RAPA treatment can mitigate the development of T2D‐induced cardiomyopathy in adult mice. Female BKS‐Leprdb mice fed diet supplemented with RAPA from 11 to 27 weeks of age showed reduced weight gain and significant reductions of fat and lean mass compared with untreated mice. No differences in plasma glucose or insulin levels were observed between groups; however, RAPA‐treated mice were more insulin sensitive (P < 0.01) than untreated mice. Urine albumin/creatinine ratio was lower in RAPA‐treated mice, suggesting reduced diabetic nephropathy and improved kidney function. Echocardiography showed significantly reduced left ventricular wall thickness in mice treated with RAPA compared with untreated mice (P = 0.02) that was consistent with reduced heart weight/tibia length ratios, reduced myocyte size and cardiac fibrosis measured by histomorphology, and reduced mRNA expression of Col1a1, a marker for cardiomyopathy. Our results suggest that inhibition of mTORC signaling is a plausible strategy for ameliorating complications of obesity and T2D, including cardiomyopathy.
Therapeutic applications of betulinic acid nanoformulations
Authors: Saneja Ankit , Arora Divya , Kumar Robin , Dubey Ravindra Dhar , Panda Amulya K. , Gupta Prem N.
Published: January 2018

Betulinic acid (BA), a naturally occurring plant‐derived pentacyclic triterpenoid, has gained attention in recent years owing to its broad‐spectrum biological and medicinal properties. Despite the pharmacological activity of BA, it has been associated with some drawbacks, such as poor aqueous solubility and short half‐life in vivo, which limit therapeutic application. To solve these problems, much work in recent years has focused on enhancing BA's aqueous solubility, half‐life, and efficacy by using nanoscale drug delivery systems. Several different kinds of nanoscale delivery systems—including polymeric nanoparticles, magnetic nanoparticles, liposomes, polymeric conjugates, nanoemulsions, cyclodextrin complexes, and carbon nanotubes—have been developed for the delivery of BA. Here, we focus on the recent developments of novel nanoformulations used to deliver BA in order to improve its efficacy.
Should vitamin B12 status be considered in assessing risk of neural tube defects?
Authors: Molloy Anne M.
Published: January 2018

There is a strong biological premise for including vitamin B12 with folic acid in strategies to prevent neural tube defects (NTDs), due to the closely interlinked metabolism of these two vitamins. For example, reduction of B12 deficiency among women of reproductive age could enhance the capacity of folic acid to prevent NTDs by optimizing the cellular uptake and utilization of natural folate cofactors. Vitamin B12 might also have an independent role in NTD prevention, such that adding it in fortification programs might be more effective than fortifying with folic acid alone. Globally, there is ample evidence of widespread vitamin B12 deficiency in low‐ and middle‐income countries, but there is also considerable divergence of vitamin B12 status across regions, likely due to genetic as well as nutritional factors. Here, I consider the evidence that low vitamin B12 status may be an independent factor associated with risk of NTDs, and whether a fortification strategy to improve B12 status would help reduce the prevalence of NTDs. I seek to identify knowledge gaps in this respect and specify research goals that would address these gaps.
Precision medicine in diabetes: an opportunity for clinical translation
Authors: Merino Jordi , Florez Jose C.
Published: January 2018

Metabolic disorders present a public health challenge of staggering proportions. In diabetes, there is an urgent need to better understand disease heterogeneity, clinical trajectories, and related comorbidities. A pressing and timely question is whether we are ready for precision medicine in diabetes. Some biological insights that have emerged during the last decade have already been used to direct clinical decision making, especially in monogenic forms of diabetes. However, much work is necessary to integrate high‐dimensional explorations into complex disease architectures, less penetrant biological alterations, and broader phenotypes, such as type 2 diabetes. In addition, for precision medicine to take hold in diabetes, reproducibility, interpretability, and actionability remain key guiding objectives. In this review, we examine how mounting data sets generated during the last decade to understand biological variability are now inspiring new venues to clarify diabetes nosology and ultimately translate findings into more effective prevention and treatment strategies.
Cardiometabolic risk in obese children
Authors: Chung Stephanie T. , Onuzuruike Anthony U. , Magge Sheela N.
Published: January 2018

Obesity in childhood remains a significant and prevalent public health concern. Excess adiposity in youth is a marker of increased cardiometabolic risk (CMR) in adolescents and adults. Several longitudinal studies confirm the strong association of pediatric obesity with the persistence of adult obesity and the future development of cardiovascular disease, diabetes, and increased risk of death. The economic and social impact of childhood obesity is further exacerbated by the early onset of the chronic disease burden in young adults during their peak productivity years. Furthermore, rising prevalence rates of severe obesity in youth from disadvantaged and/or minority backgrounds have prompted the creation of additional classification schemes for severe obesity to improve CMR stratification. Current guidelines focus on primary obesity prevention efforts, as well as screening for clustering of multiple CMR factors to target interventions. This review summarizes the scope of the pediatric obesity epidemic, the new severe obesity classification scheme, and examines the association of excess adiposity with cardiovascular and metabolic risk. We will also discuss potential questions for future investigation.
Association between periodontitis and chronic kidney disease: Systematic review and meta‐analysis
Authors: Deschamps‐Lenhardt S , Martin‐Cabezas R , Hannedouche T , Huck O
Published: January 2018

A systematic review and meta‐analysis were conducted to evaluate the association between periodontitis (PD) and chronic kidney disease (CKD) and to explore the potential influence of periodontal treatment in patients with CKD. Databases (PubMed, Web of Science, Science direct, Cochrane Database) were screened for relevant articles, focusing on the periodontal status of patients with CKD, published until December 2017. Five hundred and fifty‐three articles were identified, and 37 fulfilled the inclusion criteria and were considered in this systematic review. Seventeen articles were included in the meta‐analysis and 7 in the review focusing on the impact of periodontal treatment. Most of the identified studies indicated an increased incidence of PD in patients with CKD. Meta‐analysis showed an association between CKD and PD, and strength of this association was increased when severe PD was considered (OR = 2.39 (1.70–3.36)). The association could be observed even after adjustment for major CKD risk factors or use of precise diagnosis criteria (OR = 2.26 for severe PD (1.69–3.01)). Analysis of cohort studies indicated an incident rate ratio (IRR) of 1.73. Periodontitis is associated with CKD after multivariable adjustment. Further studies are necessary to determine whether prevention or treatment of PD can reduce the incidence and/or severity of CKD.
Recent developments in analytic Christology
Authors: Arcadi James M.
Published: January 2018

The notion that Jesus Christ is one person with two natures has been the venue of much philosophical theological work in the past 40 years. One mode of engagement with this idea has been to defend the coherence of the idea. This has been done by, for example, revising standard conceptions of divinity and humanity or predicate attribution. Another mode of engagement with the doctrine is to offer models for how the state of affairs of the Incarnation might work. This could involve retrieving models from thinkers of the past. Finally, the constructive mode applies the reasoning of the two natures/one person conception to other areas of Christian theology such as the atonement or the Eucharist. Examples of each of these modes from the contemporary analytic literature are presented.
Li Zehou's notion of subjectality as a new conception of the human self
Authors: Rošker Jana S.
Published: January 2018

Li Zehou stands among the most influential Chinese philosophers in the post‐Mao era. His notion of subjectality (zhutixing 主体性) is of paramount importance for current developments in contemporary Chinese philosophy. It belongs to the central concepts in Li's theoretical framework, around which his entire philosophical system is constructed. With his elaboration of this concept, Li expanded the problem of the self in post‐revolutionary modernism. The present article analyzes the theoretical bases of this concept, exposes its importance in the scope of contemporary Chinese theory and shows why and how it represents a call for a new humanism. Through a multidimensional comparative perspective, the author also explains why the human subject, which is based upon Li's notion of subjectality, has the potential not only to transform (post‐)modern alienation into a real “human condition,” that is, into spiritually fulfilled society of autonomous individuals but also to fill up the prevailing “vacuum of values.”
Visible Light‐Induced Radical Mediated DNA Damage
Authors: McCue Amelia C. , Moreau Whitney M. , Shell Thomas A.
Published: January 2018

Light‐responsive compounds have been used to manipulate biological systems with spatial and temporal control of the event of interest. Illumination of alkylcobalamins with green light (>500 nm) produces carbon‐centered radicals, which have been demonstrated to effectively cause DNA damage. Molecules that cause DNA and RNA strand scission are useful for studying polynucleotide structure and the binding of small molecules and proteins to polynucleotides. Most molecules that cause DNA damage in a light‐dependent manner require high energy, short wavelength ultraviolet light, which is readily absorbed by nucleotide bases causing damage to the polynucleotides. Therefore, using alkylcobalamins is advantageous for causing strand scission of polynucleotides, because they are activated by light wavelengths that are not absorbed by nucleotide bases. Green‐light illumination of methylcobalamin effectively causes DNA strand scission based on gel mobility assays. This cleavage is due to the generation of carbon‐centered radicals based on the results of a radical trapping study. In addition, synthesis of an alkylcobalamin with a DNA binding moiety, spermine, improves DNA cleavage efficacy by an order of magnitude in comparison with methylcobalamin.
Collaborating with the Machines: A Hybrid Method for Classifying Policy Documents
Authors: Loftis Matt W. , Mortensen Peter B.
Published: January 2018

Governments produce vast and growing quantities of freely available text: laws, rules, budgets, press releases, and so forth. This information flood is facilitating important, growing research programs in policy and public administration. However, tightening research budgets and the information's vast scale forces political science and public policy to aspire to do more with less. Meeting this challenge means applied researchers must innovate. This article makes two contributions for practical text coding—the process of sorting government text into researcher‐defined coding schemes. First, we propose a method of combining human coding with automated computer classification for large data sets. Second, we present a well‐known algorithm for automated text classification, the Naïve Bayes classifier, and provide software for working with it. We argue and provide evidence that this method can help applied researchers using human coders to get more from their research budgets, and we demonstrate the method using classical examples from the study of policy agendas.
Information processing speed as a mediator between psychosocial stress and global cognition in older adults
Authors: Foong Hui F. , Hamid Tengku A. , Ibrahim Rahimah , Haron Sharifah A.
Published: January 2018

Background

The link between psychosocial stress and cognitive function is complex, and previous studies have indicated that it may be mediated by processing speed. Therefore, the main aim of this study was to examine whether processing speed mediates the association between psychosocial stress and global cognition in older adults. Moreover, the moderating role of gender in this model is examined as well.

Methods

The study included 2322 community‐dwelling older adults in Malaysia who were randomly selected through a multistage proportional cluster random sampling technique. Global cognition construct was measured by the Mini‐Mental State Examination and Montreal Cognitive Assessment; psychosocial stress construct was measured by perceived stress, depression, loneliness, and neuroticism; and processing speed was assessed by the Digit Symbol Substitution Test. Structural equation modelling was used to analyze the mediation and moderation tests.

Results

Processing speed was found to partially mediate the relationship between psychosocial stress and global cognition (β in the direct model = −0.15, P < 0.001; β in the full mediation model = −0.11, P < 0.001). Moreover, the relationship between psychosocial stress and global cognition was found to be significant in men only, whereas the association between processing speed and global cognition was significant in men and women.

Conclusions

Psychosocial stress may increase the likelihood that older adults will experience poor processing capacity, which could reduce their higher level cognition. Results indicate that there is a need to develop processing capacity intervention programmes for psychologically distressed older adults to prevent them from suffering cognitive decline.
Risk of hospitalization associated with anticholinergic medication for patients with dementia
Authors: Watanabe Shuichi , Fukatsu Takahide , Kanemoto Kosuke
Published: January 2018

Background

With the ageing of the general population, demand has grown for measures to prevent hospitalization for dementia, which can exacerbate problems associated with activities of daily living in elderly individuals. Anticholinergic medication has been shown to cause falls, delirium, and cognitive impairment in aged patients. However, the risk of hospitalization associated with the administration of anticholinergics is unclear.

Methods

We analyzed the records of 61 outpatients (26 men, 35 women; mean age: 78 ± 7 years; mean follow‐up period: 420 days) diagnosed with dementia (Alzheimer’s disease: n = 45; dementia with Lewy bodies: n = 3; undifferentiated n = 13) and prescribed anti‐dementia drugs between May 2013 and December 2014. Medication history was noted, and the patients were divided into two groups according to the Anticholinergic Risk Scale: with risk (n = 13) and without risk (n = 48). Outcome was judged based on an end‐point of hospitalization or death. Kaplan–Meier survival and Cox proportional hazard analyses were performed.

Results

Eight patients with anticholinergic risk and 12 without anticholinergic risk reached the end‐point (P < 0.005). Analysis with a proportional hazard model showed that anticholinergic medication administration was related to a higher risk for reaching the end‐point (crude hazard ratio: 3.62, 95% confidence interval: 1.45–9.04, P < 0.01; adjusted hazard ratio: 4.54, 95% confidence interval: 1.03–20.0, P < 0.05). In contrast, Mini‐Mental State Examination score, Charlson Comorbidity Index, and the number of drugs were not major risk factors for hospitalization in patients with dementia.

Conclusion

The Anticholinergic Risk Scale findings were shown to be a strong predictor of hospitalization for patients with dementia. We should evaluate the anticholinergic burden before initiating anti‐dementia therapy.
Comparing the neuropsychological profiles of mild dementia with Lewy bodies and mild Alzheimer’s disease
Authors: Xu Yan , Chen Keliang , Zhao Qianhua , Guo Qihao
Published: January 2018

Background

The present study was conducted to detect neuropsychological differences and to identify discriminators between mild dementia with L
ewy bodies (DLB
) and mild A
lzheimer’s disease (AD
).

Methods

The present study included 37 mild DLB
patients, 48 mild AD
patients, and 80 healthy elderly individuals. A comprehensive battery of neuropsychological tests was administrated to assess their cognitive function. Linear stepwise discriminant analysis was used to identify the neuropsychological measures with values that could differentiate between mild DLB
and mild AD
.

Results

The mild DLB
group had greater impairments in attention, executive function, and visuospatial ability, while mild AD
patients performed significantly worse on memory tests. Linear stepwise discriminant analysis indicated that the M
emory and E
xecutive S
creening’s 5‐min delayed recall test was the best neuropsychological discriminator between mild DLB
and mild AD
.

Conclusions

Different patterns of cognitive impairment facilitate the differentiation of mild DLB
from mild AD
. For patients with mild dementia, better performance on the M
emory and E
xecutive S
creening’s 5‐min delayed recall test suggests that the diagnosis is more likely DLB
than AD
.