bluuebunny/crossref_metadata_2025 huggingface dataset:
Range and Mechanism of Encoding of Horizontal Disparity in Macaque V1
Authors: Prince S.J.D. , Cumming B. G. , Parker A. J.
Published: May 2017

The responses of single cortical neurons were measured as a function of the binocular disparity of dynamic random dot stereograms for a large sample of neurons ( n = 787) from V1 of the awake macaque. From this sample, we selected 180 neurons whose tuning curves were strongly tuned for disparity, well sampled and well described by one-dimensional Gabor functions. The fitted parameters of the Gabor functions were used to resolve three outstanding issues in binocular stereopsis. First, we considered whether tuning curves can be meaningfully divided into discrete tuning types. Careful examination of the distributions of the Gabor parameters that determine tuning shape revealed no evidence for clustering. We conclude that a continuum of tuning types is present. Second, we investigated the mechanism of disparity encoding for V1 neurons. The shape of the disparity tuning function can be used to distinguish between position-encoding (in which disparity is encoded by an interocular shift in receptive field position) and phase-encoding (in which disparity is encoded by a difference in the receptive field profile in the 2 eyes). Both position and phase encoding were found to be common. This was confirmed by an independent assessment of disparity encoding based on the measurement of disparity sensitivity for sinusoidal luminance gratings of different spatial frequencies. The contributions of phase and position to disparity encoding were compared by estimating a population average of the rate of change in firing rate per degree of disparity. When this was calculated separately for the phase and position contributions, they were found to be closely similar. Third, we investigated the range of disparity tuning in V1 as a function of eccentricity in the parafoveal range. We find few cells which are selective for disparities greater than ±1 ° even at the largest eccentricity of ∼5 °. The preferred disparity was correlated with the spatial scale of the tuning curve, and for most units lay within a ±π radians phase limit. Such a size-disparity correlation is potentially useful for the solution of the correspondence problem.
Evidence for a Widespread Brain Stem Escape Network in Larval Zebrafish
Authors: Gahtan Ethan , Sankrithi Nagarajan , Campos Jeanette B. , O'Malley Donald M.
Published: May 2017

Zebrafish escape behaviors, which typically consist of a C bend, a counter-turn, and a bout of rapid swimming, are initiated by firing of the Mauthner cell and two segmental homologs. However, after laser-ablation of the Mauthner cell and its homologs, escape-like behaviors still occur, albeit at a much longer latency. This might suggest that additional neurons contribute to this behavior. We therefore recorded the activity of other descending neurons in the brain stem using confocal imaging of cells retrogradely labeled with fluorescent calcium indicators. A large majority of identified descending neurons present in the larval zebrafish, including both ipsilaterally and contralaterally projecting reticulospinal neurons, as well as neurons from the nucleus of the medial longitudinal fasciculus, showed short-latency calcium responses after gentle taps to the head of the larva—a stimulus that reliably evokes an escape behavior. Previous studies had associated such in vivo calcium responses with the firing of action potentials, and because all responding cells have axons projecting into to spinal cord, this suggests that these cells are relaying escape-related information to spinal cord. Other identified neurons failed to show consistent calcium responses to escape-eliciting stimuli. In conjunction with previous lesion studies, these results indicate that the neural control systems for turning and swimming behaviors are widely distributed in the larval zebrafish brain stem. The degree of robustness or redundancy of this system has implications for the descending control of vertebrate locomotion.
Suppression of Neural Responses to Nonoptimal Stimuli Correlates With Tuning Selectivity in Macaque V1
Authors: Ringach D. L. , Bredfeldt C. E. , Shapley R. M. , Hawken M. J.
Published: May 2017

Neural responses in primary visual cortex (area V1) are selective for the orientation and spatial frequency of luminance-modulated sinusoidal gratings. Selectivity could arise from enhancement of the cell's response by preferred stimuli, suppression by nonoptimal stimuli, or both. Here, we report that the majority of V1 neurons do not only elevate their activity in response to preferred stimuli, but their firing rates are also suppressed by nonoptimal stimuli. The magnitude of suppression is similar to that of enhancement. There is a tendency for net response suppression to peak at orientations near orthogonal to the optimal for the cell, but cases where suppression peaks at oblique orientations are observed as well. Interestingly, selectivity and suppression correlate in V1: orientation and spatial frequency selectivity are higher for neurons that are suppressed by nonoptimal stimuli than for cells that are not. This finding is consistent with the idea that suppression plays an important role in the generation of sharp cortical selectivity. We show that nonlinear suppression is required to account for the data. However, the precise structure of the neural circuitry generating the suppressive signal remains unresolved. Our results are consistent with both feedback and (nonlinear) feed-forward inhibition.
Uniform Range of Conduction Times From the Lateral Amygdala to Distributed Perirhinal Sites
Authors: Pelletier J. Guillaume , Paré Denis
Published: May 2017

Much data indicate that the perirhinal (PRH) cortex plays a critical role in declarative memory and that the amygdala facilitates this process under emotionally arousing conditions. However, assuming that the amygdala does so by promoting Hebbian interactions in the PRH cortex is hard to reconcile with the fact that variable distances separate amygdala neurons from their PRH projection sites. Indeed, to achieve a synchronized activation of distributed PRH sites, amygdala axons should display a uniform range of conduction times, irrespective of distance to target. To determine if amygdala axons meet this condition, we measured the antidromic response latencies of lateral amygdala (LA) neurons to electrical stimuli delivered at various rostrocaudal levels of the PRH cortex in cats anesthetized with isoflurane. Although large variations in antidromic response latencies were observed, they were unrelated to the distance between the PRH stimulation sites and LA neurons. To determine whether this result was an artifact due to current spread, two control experiments were performed. First, we examined the antidromic response latency of intrinsic PRH neurons. Although we used the same methods as in the first experiment, the antidromic response latency of PRH neurons to electrical stimuli applied in the PRH cortex increased linearly with the distance between the stimulating and recording sites. Second, we measured the antidromic response latency of PRH neurons projecting to the LA. In this pathway, we also found a statistically significant correlation between conduction times and distance to target. Thus these results support the intriguing possibility that the conduction velocity and/or trajectory of LA axons are adjusted to compensate for variations in distance between the LA and distinct rostrocaudal PRH sites. We hypothesize that because of their uniform range of conduction times to the PRH cortex, LA neurons can generate short time windows of depolarization facilitating Hebbian associations between coincident, but spatially distributed, activity patterns in the PRH cortex. In this context, the temporal scatter of conduction times in the LA to PRH pathway is conceived as a mechanism used to lengthen the period of depolarization to compensate for conduction delays within intrinsic PRH pathways. In part, this mechanism might explain how the amygdala promotes memory storage in emotionally arousing conditions.
Synaptic Mechanisms Regulating the Activation of a Ca2+-Mediated Plateau Potential in Developing Relay Cells of the LGN
Authors: Lo Fu-Sun , Ziburkus Jokubas , Guido William
Published: May 2017

Using intracellular recordings in an isolated (in vitro) rat brain stem preparation, we examined the synaptic responses of developing relay neurons in the dorsal lateral geniculate nucleus (LGN). In newborn rats, strong stimulation of the optic tract (OT) evoked excitatory postsynaptic potentials (EPSPs) that gave rise to a sustained (300–1,300 ms), slow-decaying (<0.01 mV/s), depolarization (25–40 mV). Riding atop this response was a train of spikes of variable amplitude. We refer to this synaptically evoked event as a plateau potential. Pharmacology experiments indicate the plateau potential was mediated by the activation of high-threshold L-type Ca2+ channels. Synaptic activation of the plateau potential relied on N-methyl-d-aspartate (NMDA) receptor-mediated activity and the spatial and/or temporal summation of retinally evoked EPSPs. Inhibitory postsynaptic responses (IPSPs) did not prevent the expression of the plateau potential. However, GABAA receptor activity modulated the intensity of optic tract stimulation needed to evoke the plateau potential, while GABAB receptor activity affected its duration. Expression of the plateau potential was developmentally regulated, showing a much higher incidence at P1–2 (90%) than at P19–20 (1%). This was in part due to the fact that developing relay cells show a greater degree of spatial summation than their mature counterparts, receiving input from as many as 7–12 retinal ganglion cells. Early spontaneous retinal activity is also likely to trigger the plateau potential. Repetitive stimulation of optic tract in a manner that approximated the high-frequency discharge of retinal ganglion cells led to a massive temporal summation of EPSPs and the activation of a sustained depolarization (>1 min) that was blocked by L-type Ca2+ channel antagonists. These age-related changes in Ca2+ signaling may contribute to the activity-dependent refinement of retinogeniculate connections.
Cyclin D1 Restrains Oncogene-Induced Autophagy by Regulating the AMPK–LKB1 Signaling Axis
Authors: Casimiro Mathew C. , Di Sante Gabriele , Di Rocco Agnese , Loro Emanuele , Pupo Claudia , Pestell Timothy G. , Bisetto Sara , Velasco-Velázquez Marco A. , Jiao Xuanmao , Li Zhiping , Kusminski Christine M. , Seifert Erin L. , Wang Chenguang , Ly Daniel , Zheng Bin , Shen Che-Hung , Scherer Philipp E. , Pestell Richard G.
Published: May 2017

Autophagy activated after DNA damage or other stresses mitigates cellular damage by removing damaged proteins, lipids, and organelles. Activation of the master metabolic kinase AMPK enhances autophagy. Here we report that cyclin D1 restrains autophagy by modulating the activation of AMPK. In cell models of human breast cancer or in a cyclin D1–deficient model, we observed a cyclin D1–mediated reduction in AMPK activation. Mechanistic investigations showed that cyclin D1 inhibited mitochondrial function, promoted glycolysis, and reduced activation of AMPK (pT172), possibly through a mechanism that involves cyclin D1-Cdk4/Cdk6 phosphorylation of LKB1. Our findings suggest how AMPK activation by cyclin D1 may couple cell proliferation to energy homeostasis. Cancer Res; 77(13); 3391–405. ©2017 AACR.
Expansion of Tumor-Infiltrating CD8+ T cells Expressing PD-1 Improves the Efficacy of Adoptive T-cell Therapy
Authors: Fernandez-Poma Sarita M. , Salas-Benito Diego , Lozano Teresa , Casares Noelia , Riezu-Boj Jose-Ignacio , Mancheño Uxua , Elizalde Edurne , Alignani Diego , Zubeldia Natalia , Otano Itziar , Conde Enrique , Sarobe Pablo , Lasarte Juan Jose , Hervas-Stubbs Sandra
Published: May 2017

Recent studies have found that tumor-infiltrating lymphocytes (TIL) expressing PD-1 can recognize autologous tumor cells, suggesting that cells derived from PD-1+ TILs can be used in adoptive T-cell therapy (ACT). However, no study thus far has evaluated the antitumor activity of PD-1–selected TILs in vivo. In two mouse models of solid tumors, we show that PD-1 allows identification and isolation of tumor-specific TILs without previous knowledge of their antigen specificities. Importantly, despite the high proportion of tumor-reactive T cells present in bulk CD8 TILs before expansion, only T-cell products derived from sorted PD-1+, but not from PD-1− or bulk CD8 TILs, specifically recognized tumor cells. The fold expansion of PD-1+ CD8 TILs was 10 times lower than that of PD-1− cells, suggesting that outgrowth of PD-1− cells was the limiting factor in the tumor specificity of cells derived from bulk CD8 TILs. The highly differentiated state of PD-1+ cells was likely the main cause hampering ex vivo expansion of this subset. Moreover, PD-1 precisely identified marrow-infiltrating, myeloma-specific T cells in a mouse model of multiple myeloma. In vivo, only cells expanded from PD-1+ CD8 TILs contained tumor progression, and their efficacy was enhanced by PDL-1 blockade. Overall, our data provide a rationale for the use of PD-1–selected TILs in ACT. Cancer Res; 77(13); 3672–84. ©2017 AACR.
Estimation of the Number of Women Living with Metastatic Breast Cancer in the United States
Authors: Mariotto Angela B. , Etzioni Ruth , Hurlbert Marc , Penberthy Lynne , Mayer Musa
Published: May 2017

Background: Distant metastatic breast cancer (MBC), including metastases found at diagnosis (de novo) and those occurring later (recurrence), represents the most severe form of the disease, when resource utilization is most intensive. Yet, the number of women living with MBC in the United States is unknown. The objective of this article is to use population-based data to estimate the prevalence of MBC.

Methods: We used a back-calculation method to estimate MBC prevalence from U.S. breast cancer mortality and survival from the Surveillance, Epidemiology and End Results (SEER) registries. On the basis of the illness–death process, this method assumes that each observed breast cancer death is the result of MBC, either de novo or a recurrence with metastatic disease.

Results: We estimate that by January 1, 2017, there will be 154,794 women living with MBC in the United States, three in four initially diagnosed with stage I–III breast cancer who later progressed to MBC.

Median survival and 5-year relative survival for de novo MBC increased over the years, especially in younger women. We estimate a two-fold increase in 5-year relative survival rate from 18% to 36%, for women diagnosed with de novo MBC at age 15–49 between 1992–1994 and 2005–2012, respectively.

Conclusions: This study demonstrates an increasing number of women in the United States living with MBC, likely the result of improvements in treatment and aging of the U.S. population.

Impact: The increasing burden of MBC highlights the importance of documenting recurrence to foster more research into the specific needs of this understudied population. Cancer Epidemiol Biomarkers Prev; 26(6); 809–15. ©2017 AACR.
A Potential Mechanism for ADC-Induced Neutropenia: Role of Neutrophils in Their Own Demise
Authors: Zhao Hui , Gulesserian Sara , Malinao Maria Christina , Ganesan Sathish Kumar , Song James , Chang Mi Sook , Williams Melissa M. , Zeng Zhilan , Mattie Michael , Mendelsohn Brian A. , Stover David R. , Doñate Fernando
Published: May 2017

Neutropenia is a common adverse event in cancer patients treated with antibody–drug conjugates (ADC) and we aimed to elucidate the potential mechanism of this toxicity. To investigate whether ADCs affect neutrophil production from bone marrow, an in vitro assay was developed in which hematopoietic stem cells (HSC) were differentiated to neutrophils. Several antibodies against targets absent in HSCs and neutrophils were conjugated to MMAE via a cleavable valine-citrulline linker (vcMMAE-ADC) or MMAF via a noncleavable maleimidocaproyl linker (mcMMAF-ADC), and their cytotoxicity was tested in the neutrophil differentiation assay. Results showed that HSCs had similar sensitivity to vcMMAE-ADCs and mcMMAF-ADCs; however, vcMMAE-ADCs were more cytotoxic to differentiating neutrophils than the same antibody conjugated to mcMMAF. This inhibitory effect was not mediated by internalization of ADC either by macropinocytosis or FcγRs. Our results suggested that extracellular proteolysis of the cleavable valine-citrulline linker is responsible for the cytotoxicity to differentiating neutrophils. Mass spectrometry analyses indicated that free MMAE was released from vcMMAE-ADCs in the extracellular compartment when they were incubated with differentiating neutrophils or neutrophil conditioned medium, but not with HSC-conditioned medium. Using different protease inhibitors, our data suggested that serine, but not cysteine proteases, were responsible for the cleavage. In vitro experiments demonstrated that the purified serine protease, elastase, was capable of releasing free MMAE from a vcMMAE-ADC. Here we propose that ADCs containing protease cleavable linkers can contribute to neutropenia via extracellular cleavage mediated by serine proteases secreted by differentiating neutrophils in bone marrow. Mol Cancer Ther; 16(9); 1866–76. ©2017 AACR.

See related article by Zhao et al., p. 1877
Histone H3.3K27M Represses p16 to Accelerate Gliomagenesis in a Murine Model of DIPG
Authors: Cordero Francisco J. , Huang Zhiqing , Grenier Carole , He Xingyao , Hu Guo , McLendon Roger E. , Murphy Susan K. , Hashizume Rintaro , Becher Oren J.
Published: May 2017

Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive pediatric brainstem tumor genetically distinguished from adult GBM by the high prevalence of the K27M mutation in the histone H3 variant H3.3 (H3F3A). This mutation reprograms the H3K27me3 epigenetic landscape of DIPG by inhibiting the H3K27-specific histone methyltransferase EZH2. This globally reduces H3K27me2/3, critical repressive marks responsible for cell fate decisions, and also causes focal gain of H3K27me3 throughout the epigenome. To date, the tumor-driving effects of H3.3K27M remain largely unknown. Here, it is demonstrated that H3.3K27M cooperates with PDGF-B in vivo, enhancing gliomagenesis and reducing survival of p53 wild-type (WT) and knockout murine models of DIPG. H3.3K27M expression drives increased proliferation of tumor-derived murine neurospheres, suggesting that cell-cycle deregulation contributes to increased malignancy in mutant tumors. RNA sequencing on tumor tissue from H3.3K27M-expressing mice indicated global upregulation of PRC2 target genes, and a subset of newly repressed genes enriched in regulators of development and cell proliferation. Strikingly, H3.3K27M induced targeted repression of the p16/ink4a (CDKN2A) locus, a critical regulator of the G0–G1 to S-phase transition. Increased levels of H3K27me3 were observed at the p16 promoter; however, pharmacologic reduction of methylation at this promoter did not rescue p16 expression. Although DNA methylation is also present at this promoter, it is not K27M dependent. Intriguingly, inhibition of DNA methylation restores p16 levels and is cytotoxic against murine tumor cells. Importantly, these data reveal that H3.3K27M-mediated p16 repression is an important mechanism underlying the proliferation of H3.3K27M tumor cells, as in vivo cdkn2a knockout eliminates the survival difference between H3.3K27M and H3.3WT tumor-bearing mice.

Implications: This study shows that H3.3K27M mutation and PDGF signaling act in concert to accelerate gliomagenesis in a genetic mouse model and identifies repression of p16 tumor suppressor as a target of H3.3K27M, highlighting the G1–S cell-cycle transition as a promising therapeutic avenue. Mol Cancer Res; 15(9); 1243–54. ©2017 AACR.
Nasal Cavity Paraganglioma: Literature Review and Discussion of a Rare Case
Authors: de Almeida Vital Juliana Maria , de Farias Terence Pires , Dias Fernando Luiz , de Oliveira Juliana Fernandes , Miranda da Paixão José Gabriel , de Cavalcanti Siebra Paulo José , Lopes Moraes Arli Regina
Published: May 2017

Paragangliomas can be found from the skull base to the sacrum. Sinonasal paragangliomas are infrequent. A 16-year-old female reported spontaneous discrete bilateral epistaxis once a month beginning when she was 3 years of age. Computed tomography showed an expansive hypervascular mass occupying the right nasal cavity and nasopharynx. Sinonasal paragangliomas usually occur in middle-aged women. Radiologic investigation is essential for the diagnosis of sinonasal paragangliomas and evaluating extension of the lesion. Endoscopic and conventional approaches are effective, and preoperative embolization is paramount for reducing bleeding risk. Histopathological features cannot differentiate benign from malignant paragangliomas, and since metastasis may eventually occur, follow-up must be carried out for a long period of time.
Evaluation of Hypocaloric Diet With Protein Supplementation in Middle-Aged Sarcopenic Obese Women: A Pilot Study
Authors: Sammarco Rosa , Marra Maurizio , Di Guglielmo Maria Luisa , Naccarato Marianna , Contaldo Franco , Poggiogalle Eleonora , Donini Lorenzo Maria , Pasanisi Fabrizio
Published: May 2017

Objective: The aim of this study was to evaluate the efficacy of a nutritional program, which is characterized by a different modulation of proteins, in adult patients with sarcopenic obesity. Methods: We studied 18 obese women aged 41-74 years. Obesity was diagnosed as fat mass > 34.8% and sarcopenia was defined when lean body mass was <90% of the subject's ideal fat free mass. All subjects were randomly assigned to different nutritional interventions: Hypocaloric diet plus placebo (A) and hypocaloric high-protein diet (1.2-1.4 g / kg body weight reference / day) (B). Anthropometric measurements, body composition, resting energy expenditure, handgrip test, Short Physical Performance Battery (SPPB), and SF-36 questionnaire were evaluated at baseline and after 4 months. Results: Weight significantly decreased in both groups. Women with high-protein diet preserved lean body mass compared to low-calorie diet and improved significantly muscle strength; SPPB score did not change in both groups. SF-36 test showed a significant change for general health after 4 months in group B. Conclusions: In our study, sarcopenic obese patients with high-protein diet showed an improvement in muscle strength. Furthermore, dietary protein enrichment may represent a protection from the risk of sarcopenia following a hypocaloric diet.
Trends in Gene Expression Profiling for Prostate Cancer Risk Assessment: A Systematic Review
Authors: Chen Zhaoyi , Gerke Travis , Bird Victoria , Prosperi Mattia
Published: May 2017

Objectives: The aim of the study is to review biotechnology advances in gene expression profiling on prostate cancer (PCa), focusing on experimental platform development and gene discovery, in relation to different study designs and outcomes in order to understand how they can be exploited to improve PCa diagnosis and clinical management. Methods: We conducted a systematic literature review on gene expression profiling studies through PubMed/MEDLINE and Web of Science between 2000 and 2016. Tissue biopsy and clinical gene profiling studies with different outcomes (e.g., recurrence, survival) were included. Results: Over 3,000 papers were screened and 137 full-text articles were selected. In terms of technology used, microarray is still the most popular technique, increasing from 50 to 70% between 2010 and 2015, but there has been a rise in the number of studies using RNA sequencing (13% in 2015). Sample sizes have increased, as well as the number of genes that can be screened all at once, but we have also observed more focused targeting in more recent studies. Qualitative analysis on the specific genes found associated with PCa risk or clinical outcomes revealed a large variety of gene candidates, with a few consistent cross-studies. Conclusions: The last 15 years of research in gene expression in PCa have brought a large volume of data and information that has been decoded only in part, but advancements in high-throughput sequencing technology are increasing the amount of data that can be generated. The variety of findings warrants the execution of both validation studies and meta-analyses. Genetic biomarkers have tremendous potential for early diagnosis of PCa and, if coupled with other diagnostics (e.g., imaging), can effectively be used to concretize less-invasive, personalized prediction of PCa risk and progression.
The Crossed Flexor Plantar Response in Patients with Klippel-Feil Syndrome
Authors: Sadnicka Anna , Farmer Simon F.
Published: May 2017

The plantar reflex is one of most important and widely tested components of the neurological examination. We describe 3 subjects with Klippel-Feil syndrome and mirror movements where unilateral cutaneous stimulation of the foot leads to flexor plantar responses in both feet. We discuss the evidence which suggests that this “crossed flexor” plantar response reveals a transcortical pathway for the flexor plantar response.
Association between Chronic Kidney Disease and Risk of Cataract: A Nationwide Retrospective Cohort Study
Authors: Liu Yin-Tzu , Hung Tzu-Yao , Lee Yi-Kung , Huang Ming-Yuan , Hsu Chen-Yang , Su Yung-Cheng
Published: May 2017

Background: Previous studies have established a relationship between chronic kidney disease (CKD) and cataract, but the relationship between the severity of renal impairment and risk of cataract is uncertain. This study investigates the relationship between the severity of renal disease and cataract in a nationwide sample from Taiwan. Methods: The cohort from 1-million National Health Insurance beneficiaries from Taiwan was retrospectively analyzed. All adult beneficiaries were followed from January 1, 2005 until December 31, 2013, to identify patients who underwent cataract surgeries. On the basis of the ambulatory care records, those diagnosed with CKD (ICD-9-CM code: 585) during the follow-up period were enrolled as CKD patients after careful evaluation. Each patient with CKD was age- and gender-matched with 4 individuals who did not have CKD. Cox regression models were applied to compare the hazard of cataract surgery in individuals with and without CKD. Subgroup analysis was used to compare patients with end-stage renal disease (ESRD) with age- and gender-matched non-CKD individuals. ESRD was defined by CKD patients who need regular renal replacement therapy. The same method was applied to evaluate hazard ratios (HRs). Results: After age and gender matching, there were 11,881 patients in the CKD group and 47,524 in the non-CKD group. After control for possible confounding, the adjusted HR (aHR) of cataract was 1.84 (95% CI 1.73-1.95) for the CKD group. Subgroup analysis of patients with ESRD (n = 3,209) and non-CKD individuals (n = 12,836), with matching done on the basis of age and gender, indicated an aHR of cataract was 2.33 (95% CI 2.10-2.59) for the ESRD group. Conclusions: This study indicates a relationship between CKD and cataract, and suggests that the risk for cataract increases with the severity of renal impairment.
Racial and Ethnic Differences in Mortality Associated with Serum Potassium in a Large Hemodialysis Cohort
Authors: Kim Taehee , Rhee Connie M. , Streja Elani , Soohoo Melissa , Obi Yoshitsugu , Chou Jason A. , Tortorici Amanda R. , Ravel Vanessa A. , Kovesdy Csaba P. , Kalantar-Zadeh Kamyar
Published: May 2017

Background: Hyperkalemia is observed in chronic kidney disease patients and may be a risk factor for life-threatening arrhythmias and death. Race/ethnicity may be important modifiers of the potassium-mortality relationship in maintenance hemodialysis (MHD) patients given that potassium intake and excretion vary among minorities. Methods: We examined racial/ethnic differences in baseline serum potassium levels and all-cause and cardiovascular mortality using Cox proportional hazard models and restricted cubic splines in a cohort of 102,241 incident MHD patients. Serum potassium was categorized into 6 groups: ≤3.6, >3.6 to ≤4.0, >4.0 to ≤4.5 (reference), >4.5 to ≤5.0, >5.0 to ≤5.5, and >5.5 mEq/L. Models were adjusted for case-mix and malnutrition-inflammation cachexia syndrome (MICS) covariates. Results: The cohort was composed of 50% whites, 34% African-Americans, and 16% Hispanics. Hispanics tended to have the highest baseline serum potassium levels (mean ± SD: 4.58 ± 0.55 mEq/L). Patients in our cohort were followed for a median of 1.3 years (interquartile range 0.6-2.5). In our cohort, associations between higher potassium (>5.5 mEq/L) and higher mortality risk were observed in African-American and whites, but not Hispanic patients in models adjusted for case-mix and MICS covariates. While in Hispanics only, lower serum potassium (<3.6 mEq/L) levels were associated with higher mortality risk. Similar trends were observed for cardiovascular mortality. Conclusions: Higher potassium levels were associated with higher mortality risk in white and African-American MHD patients, whereas lower potassium levels were associated with higher death risk in Hispanics. Further studies are needed to determine the underlying mechanisms for the differential association between potassium and mortality across race/ethnicity.
Partial Hepatectomy with Middle Hepatic Vein Reconstruction Using a Left Inferior Vena Cava Graft
Authors: Kawamoto Yusuke , Ome Yusuke , Kawamoto Kazuyuki
Published: May 2017

Duplicated inferior vena cava (IVC) is a rare congenital anomaly. We describe the utility of a new graft from the left IVC in a patient with duplicated IVC for reconstructing the middle hepatic vein (MHV) after partial hepatectomy with MHV resection. A 67-year-old woman with hepatitis C was found to have a liver tumor. Magnetic resonance imaging confirmed that the tumor, which was attached to the MHV, was hepatocellular carcinoma. Central bisectionectomy (S4, S5, and S8 resection) could not be tolerated because of poor liver function and a low future liver remnant volume. Therefore, partial hepatectomy with MHV resection was performed. The left IVC was harvested as a venous graft and was substituted for the resected MHV. She recovered uneventfully and was discharged on postoperative day 12. To the best of our knowledge, this is the first report of using the left IVC as a venous graft. The left IVC is a good candidate graft for the MHV or for portal vein reconstruction because of its length, diameter, and easy harvesting (it did not require an extra incision) in a patient with duplicated IVC.
Effect of 1,25-(OH)2D3 on Proliferation of Fibroblast-Like Synoviocytes and Expressions of Pro-Inflammatory Cytokines through Regulating MicroRNA-22 in a Rat Model of Rheumatoid Arthritis
Authors: Fan Ping , He Lan , Hu Nan , Luo Jing , Zhang Jing , Mo Ling-Fei , Wang Yan-Hua , Pu Dan , Lv Xiao-Hong , Hao Zhi-Ming , Ding Chang-Hai , Xue Wu-Jun , Li Yang
Published: May 2017

Objective: This study aims to investigate the regulatory mechanism of 1,25-(OH)2D3 on the proliferation of fibroblast-like synoviocytes (FLS) and expressions of pro-inflammatory cytokines in rheumatoid arthritis (RA) rats via microRNA-22 (miR-22). Methods: A rat model of RA was established with a subcutaneous injection of type II collagen. After treated with different concentrations of 1,25-(OH)2D3 the proliferation of FLS was estimated by the MTT method, and the optimal concentration of 1,25-(OH)2D3 was selected for further experiments. Cell proliferation was detected by MTT. Cell cycle and apoptosis were analyzed by FCM. The IL-1β, IL-6, IL-8, and PGE2 protein expressions were determined by ELISA, and MMP-3, INOS, and Cox-2 mRNA expressions were measured by qRT-PCR. Results: The rat model of RA was successfully established. Compared with the blank group, the 1,25-(OH)2D3 and miR-22 inhibitors groups exhibited higher proliferation inhibition and apoptosis rates, lower levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and PGE2), and decreased mRNA expressions of MMP-3, INOS, and Cox-2. The miR-22 mimics group had lower proliferation inhibition and apoptosis rates, elevated expressions of pro-inflammatory cytokines and MMP-3, INOS, and Cox-2 than the blank group. In contrast to the 1,25-(OH)2D3 group, the proliferation inhibition and apoptosis rates were down-regulated, and the expressions of pro-inflammatory cytokines and MMP-3, INOS, and Cox-2 were up-regulated in the 1,25-(OH)2D3 + miR-22 mimics group. Conclusion: Our study demonstrated that 1,25-(OH)2D3 inhibits the proliferation of FLS and alleviates inflammatory response in RA rats by down-regulating miR-22.
Epidemiology of Amyotrophic Lateral Sclerosis in the Republic of Cyprus: A 25-Year Retrospective Study
Authors: Demetriou Christiana A. , Hadjivasiliou Petros M. , Kleopa Kleopas A. , Christou Yiolanda P. , Leonidou Eleni , Kyriakides Theodoros , Zamba-Papanicolaou Eleni
Published: May 2017

Introduction: Amyotrophic lateral sclerosis (ALS) is a rare, rapidly progressive neurodegenerative disease. Despite wide variability in the incidence and prevalence of ALS, there is evidence of positive temporal trends and an increase in incidence with age. The aim of this study was to conduct a detailed epidemiological investigation of ALS in Cyprus. Methods: All registered Cypriot ALS patients in the Republic of Cyprus from January 1985 until December 2014 were included. Socio-demographic information was extracted from patient files. Results: The study identified 179 ALS patients, of whom 7 had a positive family history. The mean age at onset was 58.6 years and a slight male predominance was observed. Average annual crude incidence was 1.26 cases/100,000 person-years and at the beginning of 2015, prevalence of ALS was 7.9 cases/100,000 population. Both incidence and prevalence displayed an increasing trend, even after age-standardization of incidence rates. Conclusions: Incidence, prevalence and main socio-demographic characteristics of ALS in Cyprus were similar to those of other European countries, without any geographic clustering of the disease. Additionally, an increased incidence through the years was confirmed. However, observations such as a higher male prevalence and a younger mean age of onset compared to published literature require further investigation.
Greater Frequency of Fruit and Vegetable Consumption Is Associated With Lower Prevalence of Peripheral Artery Disease
Authors: Heffron Sean P. , Rockman Caron B. , Adelman Mark A. , Gianos Eugenia , Guo Yu , Xu Jin Feng , Berger Jeffrey S.
Published: May 2017

Objective—

Although fruit and vegetable (F&V) consumption is associated with lower risk of coronary heart disease and stroke, its association with peripheral artery disease (PAD) is less certain. We, thus, sought to characterize F&V intake and investigate the association between F&V consumption and presence of PAD in a large community sample.

Approach and Results—

Self-referred participants at >20 000 US sites who completed medical and lifestyle questionnaires were evaluated by screening ankle brachial indices for PAD (ankle brachial index ≤0.9). Among 3 696 778 individuals, mean age was 64.1±10.2 years and 64.1% were female. Daily consumption of ≥3 servings of F&V was reported by 29.2%. Increasing age, female sex, white race, never smoking, being currently married, physical activity, increasing income, and frequent consumption of fish, nuts, and red meat were positively associated with daily consumption of F&V. After multivariable adjustment, there was a stepwise inverse association between F&V intake and PAD. Participants reporting daily intake of ≥3 servings of F&V had 18% lower odds of PAD than those reporting less than monthly consumption. In unadjusted and multivariable-adjusted models, the inverse association with F&V became stronger as ankle brachial index decreased. When stratified by smoking status, the association was present only among those subjects who currently or formerly smoked tobacco.

Conclusions—

Our study demonstrates an inverse association of F&V consumption with prevalent PAD and overall low F&V consumption. These observations suggest the need to further efforts to increase F&V consumption and for more rigorous evaluation of the role of F&V in PAD prevention.
Apolipoprotein A-I Mimetic Peptides
Authors: Ditiatkovski Michael , Palsson Jonatan , Chin-Dusting Jaye , Remaley Alan T. , Sviridov Dmitri
Published: May 2017

Objective—

Apolipoprotein A-I (apoA-I) mimetic peptides have antiatherogenic properties of high-density lipoprotein in vitro and have been shown to inhibit atherosclerosis in vivo. It is unclear, however, if each in vitro antiatherogenic property of these peptides translates to a corresponding activity in vivo, and if so, which of these contributes most to reduce atherosclerosis.

Approach and Results—

The effect of 7 apoA-I mimetic peptides, which were developed to selectively reproduce a specific component of the antiatherogenic properties of apoA-I, on the development of atherosclerosis was investigated in apolipoprotein E–deficient mice fed a high-fat diet for 4 or 12 weeks. The peptides include those that selectively upregulate cholesterol efflux, or are anti-inflammatory, or have antioxidation properties. All the peptides studied effectively inhibited the in vivo development of atherosclerosis in this model to the same extent. However, none of the peptides had the same selective effect in vivo as they had exhibited in vitro. None of the tested peptides affected plasma lipoprotein profile; capacity of plasma to support cholesterol efflux was increased modestly and similarly for all peptides.

Conclusions—

There is a discordance between the selective in vitro and in vivo functional properties of apoA-I mimetic peptides, and the in vivo antiatherosclerotic effect of apoA-I-mimetic peptides is independent of their in vitro functional profile. Comparing the properties of apoA-I mimetic peptides in plasma rather than in the lipid-free state is better for predicting their in vivo effects on atherosclerosis.
Circulating MicroRNA-125b Predicts the Presence and Progression of Uremic Vascular Calcification
Authors: Chao Chia-Ter , Liu You-Pi , Su Sheng-Fang , Yeh Hsiang-Yuan , Chen Hsuan-Yu , Lee Pei-Jung , Chen Wan-Jiun , Lee Yee-Ming , Huang Jenq-Wen , Chiang Chih-Kang , Hung Kuan-Yu , Chen Huei-Wen
Published: May 2017

Objective—

Vascular calcification (VC) is a major cause of mortality in patients with end-stage renal diseases. Biomarkers to predict the progression of VC early are in urgent demand.

Approach and Results—

We identified circulating, cell-free microRNAs as potential biomarkers using in vitro VC models in which both rat and human aortic vascular smooth muscle cells were treated with high levels of phosphate to mimic uremic hyperphosphatemia. Using an Affymetrix microRNA array, we found that miR-125b and miR-382 expression levels declined significantly as biomineralization progressed, but this decline was only observed for miR-125b in the culture medium. A time-dependent decrease in aortic tissue and serum miR-125b levels was also found in both ex vivo and in vivo renal failure models. We examined the levels of circulating, cell-free miR-125b in sera from patients with end-stage renal diseases (n=88) and found an inverse association between the severity of VC and the circulating miR-125b level, irrespective of age or mineral-related hormones (odds ratio, 0.71;
P
=0.03). Furthermore, serum miR-125b levels on enrollment can predict VC progression years later (for high versus low, odds ratio, 0.14;
P
<0.01; for the highest versus lowest tertile and middle versus lowest tertile, odds ratio, 0.55 and 0.13;
P
=0.3 and <0.01, respectively). The uremic VC prediction efficacy using circulating miR-125b levels was also observed in an independent cohort (n=135).

Conclusions—

The results suggest that serum miR-125b levels are associated with VC severity and serve as a novel predictive marker for the risk of uremia-associated calcification progression.
Elucidating Opposites
Authors: Cunningham Dawn
Published: May 2017

A religious diptych provided medieval people with opportunities to access the transcendental and to engage in meditation on spiritual routes to salvation. The binary format of the diptych lent itself to pairings of images that could include oppositions or iconographic contradictions. By manipulating these pairings, artists and patrons could enhance the complexity of the theological messages as well as of the relationship between art and user. Like many Gothic diptychs from Italy, an early-fourteenth-century example by Giotto is comprised of a Crucifixion and a vision of Mary’s heavenly court. The celestial group around the Virgin and child includes seven prominent personifications of the virtues. By properly identifying these moral qualities through comparisons with Giotto’s other works and by examining the oppositions they possibly addressed, we can elucidate some of the spiritual concerns of the original patron(s) who paid for and engaged with this diptych.
Loop-mediated isothermal amplification (LAMP) for detection of the red ring nematode, Bursaphelenchus cocophilus
Authors: Ide Tatsuya , Kanzaki Natsumi , Parra Giraldo Pedro Pablo , Giblin-Davis Robin M.
Published: May 2017

As a first step in developing a quick, accurate and simple method for the diagnosis of red ring disease, the loop-mediated isothermal amplification (LAMP)-based identification procedure was applied to the causative agent,Bursaphelenchuscocophilus. Two LAMP primer sets were designed using two loci of ribosomal RNA genes,i.e., D2-D3 expansion segments of the large subunit (D2-D3 LSU), and internal transcribed spacers (ITS). Within those two sets of primers, the D2-D3 LSU primer set successfully yielded amplicons fromB. cocophilusnematode lysate prepared from 3-year-old DESS-fixed specimens. The specificity of the primers was examined using 18 species of confamilial Aphelenchoididae nematodes and primer sensitivity was tested using a diluted series ofB. cocophiluslysate. The primer set did not amplify the DNA from other aphelenchoidids, and sensitivity was achieved by ‘1:100 diluted’B. cocophilusDNA (roughly 1/1500 of total DNA from a single third-stage juvenile).
Being-together as a Basic Given: Finding New Ways in Youth Ministry in a Time of Transition
Authors: van Wijnen Harmen , Barnard Marcel
Published: May 2017

Adolescence can be characterised as the process of finding the balance between the questions about identity (‘Who am I?’) and togetherness (‘Who am I with?’). The social environment of adolescents has a significant influence on this process. This environment, however, is in transition: from organisations to open networks with new forms of relationships and connections for adolescents. This transition also influences the field of youth ministry. This article considers the role small groups of adolescents can play in youth ministry in this changing social context. Based on qualitative research conducted amongst five small groups of adolescents, this article argues that togetherness is important through undirected being-together, based on emotional and affectual bonds. The results of this research are related to Maffesoli’s theory of tribalisation: being-together precedes formal organising. Being-together is a basic given and an important factor to consider in youth ministry.
Common Actions: Participatory Action Research as a Practice for Promoting Positive Social Action among and between New Canadian Church Planters and Denominational Leaders
Authors: Chapman Mark D. , Watson James W.
Published: May 2017

The Greater Toronto Area remains the major immigrant destination centre in Canada. New Canadians are welcomed but not necessarily well integrated into the lives of churches. Our experience and research has shown that this lack of integration can extend to new Canadians who start churches yet are not integrated with denominations or church planting organizations. The New Canadian Church Planter project is an ongoing participatory action research project that brings together new Canadian church planters and denominational leaders as equals. It engages these groups in conversation to identify issues of concern, facilitate shared learning, and promote positive social action. This paper uses data from that project to explore the effectiveness of participatory action research in facilitating those objectives. The project was effective at breaking down isolation, encouraging limited collaboration, developing localized resource sharing, and in disseminating learning but not at developing positive social action external to the meetings themselves.
‘Every Wife has a Church in her Home’: The Family and the Church in the American ‘Quiverfull’ Movement
Authors: McGowin Emily Hunter
Published: May 2017

‘Quiverfull’ is shorthand for a religious phenomenon that emerged within the networks of the Christian homeschooling movement in America over the past forty years. Quiverfull names a subculture of evangelical Christians whose lived religion includes three central practices: prolific childbirth, homeschooling, and patriarchy. Based upon two years of ethnographic research among Quiverfull families, the following essay explores the interplay between the family and the church within the subculture. Building on an early argument of Colleen McDannell, it is argued that within the context of the Quiverfull subculture and their particular construction of the family, the constitutive practice of homeschooling results in a transformed ecclesiology. The family functions as a ‘mini-church,’ headed by the father and mother who carry out the work of worship, spiritual formation, and evangelism on their own terms through the practice of homeschooling.
A revision and recircumscription of Begonia Section Pilderia including one new species
Authors: MOONLIGHT P. W. , JARA-MUÑOZ A.
Published: May 2017

Novel phylogenetic data is used to show that the poorly-known species Begonia glandulifera and Begonia mariannensis form a clade with Begonia buddleiifolia, the type species of Begonia section Pilderia. A unique combination of characters is identified in this group and used to re-circumscribe the section to include these species, and two morphologically similar species: Begonia jenmanii, and Begonia humilliana. A new species is described herein as Begonia tepuiensis sp. nov. from a single tepui in the Amazonas State of Venezuela. A full taxonomic revision and key to the species of Begonia section Pilderia is presented and we assign all species to IUCN Red List categories.ResumenSe usaron nuevos datos filogenéticos para mostrar que las especies pobremente conocidas: Begonia glandulifera y Begonia mariannensis forman un clado con Begonia buddleiifolia, la especie tipo de Begonia sección Pilderia. Se identificaron una combinación única de caracteres en este grupo, que fueron usados para re-circunscribir la sección incluyendo estas especies, y dos especies morfológicamente similares: Begonia jenmanii y Begonia humilliana. Se describe una nueva especie, Begonia tepuiensis sp. nov. de un tepui en el estado Amazonas de Venezuela. Se presenta también una revisión taxonómica completa y una clave para las especies de Begonia sección Pilderia y asignamos todas las especies a categorías de la Lista Roja de la UICN.
Bredia changii, a new species of Melastomataceae from Jiangxi, China
Authors: ZHAO WANYI , FAN QIANG , YE HUAGU , ZHAN XUANHUAI , LIAO WENBO
Published: May 2017

A new species, Bredia changii W.Y. Zhao, X.H. Zhan & W.B. Liao (Melastomataceae) is described from Jiangxi Province, China. Bredia changii is distinguished from other species of Bredia by its slender, creeping stem and terminal, solitary flower (seldom two flowers) and stamens almost equal in shape and length. The species is most similar to Bredia microphylla, which differs from the latter by the leaves 2–3.5 × 1.7–3.2 cm, papery, the margin obviously toothed, and homomorphic stamens, the connective without a short spur. The morphological characters of Fordiophyton repens are also similar to Bredia changii, but the stamens of F. repens are obviously dimorphic.