bluuebunny/crossref_metadata_2025 huggingface dataset:
Aerobic exercise training does not alter vascular structure and function in chronic obstructive pulmonary disease
Authors: Gelinas Jinelle C. , Lewis Nia C. , Harper Megan I. , Melzer Bernie , Agar Gloria , Rolf J. Douglass , Eves Neil D.
Published: August 2017

New Findings

What is the central question of this study?

Chronic obstructive pulmonary disease (COPD) is associated with endothelial dysfunction, arterial stiffness and systemic inflammation, which are linked to increased cardiovascular disease risk. We asked whether periodized aerobic exercise training could improve vascular structure and function in patients with COPD.

What is the main finding and its importance?

Eight weeks of periodized aerobic training did not improve endothelial function, arterial stiffness or systemic inflammation in COPD, despite improvements in aerobic capacity, blood pressure and dyspnoea. Short‐term training programmes may not be long enough to improve vascular‐related cardiovascular risk in COPD.

Chronic obstructive pulmonary disease (COPD) has been associated with endothelial dysfunction and arterial stiffening, which are predictive of future cardiovascular events. Although aerobic exercise improves vascular function in healthy individuals and those with chronic disease, it is unknown whether aerobic exercise can positively modify the vasculature in COPD. We examined the effects of 8 weeks of periodized aerobic training on vascular structure and function and inflammation in 24 patients with COPD (age, 69 ± 7 years; forced expiratory volume in 1 second as a percentage of predicted (FEV1%pred), 68 ± 19%) and 20 matched control subjects (age, 64 ± 5 years; FEV1%pred, 113 ± 16%) for comparison. Endothelial function was measured using brachial artery flow‐mediated dilatation, whereas central and peripheral pulse wave velocity, carotid artery intima–media thickness, carotid compliance, distensibility and β‐stiffness index were measured using applanation tonometry and ultrasound. Peak aerobic power () was measured using an incremental cycling test. Upper and lower body cycling training was performed three times per week for 8 weeks, and designed to optimize vascular adaptation by increasing and sustaining vascular shear stress. Flow‐mediated dilatation was not increased in COPD patients (+0.15 ± 2.27%, P = 0.82) or control subjects (+0.34 ± 3.20%, P = 0.64) and was not different between groups (P = 0.68). No significant improvements in central pulse wave velocity (COPD, +0.30 ± 1.79 m s−1 versus control subjects, −0.34 ± 1.47 m s−1) or other markers of vascular structure or function were found within or between groups. The increased significantly in COPD and control subjects, and was greater in control subjects (1.6 ± 1.4 versus 4.1 ± 3.7 ml kg min−1, P = 0.003), while blood pressure and dyspnoea were reduced in COPD patients (P < 0.05). These findings demonstrate that 8 weeks of aerobic training improved cardiorespiratory fitness and blood pressure in COPD but had little effect on other established markers of cardiovascular disease risk.
Defining the neural fulcrum for chronic vagus nerve stimulation: implications for integrated cardiac control
Authors: Ardell Jeffrey L. , Nier Heath , Hammer Matthew , Southerland E. Marie , Ardell Christopher L. , Beaumont Eric , KenKnight Bruce H. , Armour J. Andrew
Published: September 2017

Key points

The evoked cardiac response to bipolar cervical vagus nerve stimulation (VNS) reflects a dynamic interaction between afferent mediated decreases in central parasympathetic drive and suppressive effects evoked by direct stimulation of parasympathetic efferent axons to the heart.

The neural fulcrum is defined as the operating point, based on frequency–amplitude–pulse width, where a null heart rate response is reproducibly evoked during the on‐phase of VNS.

Cardiac control, based on the principal of the neural fulcrum, can be elicited from either vagus.

Beta‐receptor blockade does not alter the tachycardia phase to low intensity VNS, but can increase the bradycardia to higher intensity VNS.

While muscarinic cholinergic blockade prevented the VNS‐induced bradycardia, clinically relevant doses of ACE inhibitors, beta‐blockade and the funny channel blocker ivabradine did not alter the VNS chronotropic response.

While there are qualitative differences in VNS heart control between awake and anaesthetized states, the physiological expression of the neural fulcrum is maintained.

Vagus nerve stimulation (VNS) is an emerging therapy for treatment of chronic heart failure and remains a standard of therapy in patients with treatment‐resistant epilepsy. The objective of this work was to characterize heart rate (HR) responses (HRRs) during the active phase of chronic VNS over a wide range of stimulation parameters in order to define optimal protocols for bidirectional bioelectronic control of the heart. In normal canines, bipolar electrodes were chronically implanted on the cervical vagosympathetic trunk bilaterally with anode cephalad to cathode (n = 8, ‘cardiac’ configuration) or with electrode positions reversed (n = 8, ‘epilepsy’ configuration). In awake state, HRRs were determined for each combination of pulse frequency (2–20 Hz), intensity (0–3.5 mA) and pulse widths (130–750 μs) over 14 months. At low intensities and higher frequency VNS, HR increased during the VNS active phase owing to afferent modulation of parasympathetic central drive. When functional effects of afferent and efferent fibre activation were balanced, a null HRR was evoked (defined as ‘neural fulcrum’) during which HRR ≈ 0. As intensity increased further, HR was reduced during the active phase of VNS. While qualitatively similar, VNS delivered in the epilepsy configuration resulted in more pronounced HR acceleration and reduced HR deceleration during VNS. At termination, under anaesthesia, transection of the vagi rostral to the stimulation site eliminated the augmenting response to VNS and enhanced the parasympathetic efferent‐mediated suppressing effect on electrical and mechanical function of the heart. In conclusion, VNS activates central then peripheral aspects of the cardiac nervous system. VNS control over cardiac function is maintained during chronic therapy.
Mesoscale Physicochemical Interactions in Lithium–Sulfur Batteries: Progress and Perspective
Authors: Liu Zhixiao , Mistry Aashutosh , Mukherjee Partha P.
Published: August 2017

The shuttle effect and poor conductivity of the discharge products are among the primary impediments and scientific challenges for lithium–sulfur batteries. The lithium–sulfur battery is a complex energy storage system, which involves multistep electrochemical reactions, insoluble polysulfide precipitation in the cathode, soluble polysulfide transport, and self-discharge caused by chemical reactions between polysulfides and Li metal anode. These phenomena happen at different length and time-scales and are difficult to be entirely gauged by experimental techniques. In this paper, we reviewed the multiscale modeling studies on lithium–sulfur batteries: (1) the atomistic simulations were employed to seek alternative materials for mitigating the shuttle effect; (2) the growth kinetics of Li2S film and corresponding surface passivation were investigated by the interfacial model based on findings from atomistic simulations; (3) the nature of Li2S2, which is the only solid intermediate product, was revealed by the density functional theory simulation; and (4) macroscale models were developed to analyze the effect of reaction kinetics, sulfur loading, and transport properties on the cell performance. The challenge for the multiscale modeling approach is translating the microscopic information from atomistic simulations and interfacial model into the meso-/macroscale model for accurately predicting the cell performance.
Muscle Function and Coordination of Stair Ascent
Authors: Harper Nicole G. , Wilken Jason M. , Neptune Richard R.
Published: August 2017

Stair ascent is an activity of daily living and necessary for maintaining independence in community environments. One challenge to improving an individual's ability to ascend stairs is a limited understanding of how lower-limb muscles work in synergy to perform stair ascent. Through dynamic coupling, muscles can perform multiple functions and require contributions from other muscles to perform a task successfully. The purpose of this study was to identify the functional roles of individual muscles during stair ascent and the mechanisms by which muscles work together to perform specific subtasks. A three-dimensional (3D) muscle-actuated simulation of stair ascent was generated to identify individual muscle contributions to the biomechanical subtasks of vertical propulsion, anteroposterior (AP) braking and propulsion, mediolateral control and leg swing. The vasti and plantarflexors were the primary contributors to vertical propulsion during the first and second halves of stance, respectively, while gluteus maximus and hamstrings were the primary contributors to forward propulsion during the first and second halves of stance, respectively. The anterior and posterior components of gluteus medius were the primary contributors to medial control, while vasti and hamstrings were the primary contributors to lateral control during the first and second halves of stance, respectively. To control leg swing, antagonistic muscles spanning the hip, knee, and ankle joints distributed power from the leg to the remaining body segments. These results compliment previous studies analyzing stair ascent and provide further rationale for developing targeted rehabilitation strategies to address patient-specific deficits in stair ascent.
Design and Kinematic Analysis of a Novel 3UPS/RPU Parallel Kinematic Mechanism With 2T2R Motion for Knee Diagnosis and Rehabilitation Tasks
Authors: Araujo-Gómez Pedro , Mata Vicente , Díaz-Rodríguez Miguel , Valera Angel , Page Alvaro
Published: September 2017

This paper proposes a two translational and two rotational (2T2R) four-degrees-of-freedom (DOF) parallel kinematic mechanism (PKM) designed as a knee rehabilitation and diagnosis mechatronics system. First, we establish why rehabilitation devices with 2T2R motion are required, and then, we review previously proposed parallel mechanisms with this type of motion. After that, we develop a novel proposal based on the analysis of each kinematic chain and the Grübler–Kutzbach criterion. Consequently, the proposal consists of a central limb with revolute-prismatic-universal (RPU) joints and three external limbs with universal-prismatic-spherical (UPS) joints. The Screw theory analysis verifies the required mobility of the mechanism. Also, closed-loop equations enable us to put forward the closed-form solution for the inverse-displacement model, and a numerical solution for the forward-displacement model. A comparison of the numerical results from five test trajectories and the solution obtained using a virtual prototype built in msc-adams shows that the kinematic model represents the mechanism's motion. The analysis of the forward-displacement problem highlights the fact that the limbs of the mechanism should be arranged asymmetrically. Moreover, the Screw theory makes it possible to obtain the Jacobian matrix which provides insights into the analysis of the mechanism's workspace. The results show that the proposed PKM can cope with the required diagnosis and rehabilitation task. The results provide the guidelines to build a first prototype of the mechanism which enables us to perform initial tests on the robot.
Fourier transform infrared spectroscopy of trifluoroiodomethane plasma
Authors: Fagioli Cassius J. F. , Urrabazo David , Goeckner Matthew J.
Published: August 2017

Fluorocarbon species (CxFy) are commonly used in plasma etch processes. Trifluoroiodomethane (CF3I) might also be used as an etch gas, but there is a limited understanding as to how it will react. In this article, the authors examine the creation of CxFy daughter species from CF3I under different plasma conditions. Here, Fourier transform infrared spectroscopy (FTIR) was used to measure the concentration of various gas species. Readings were taken at different plasma powers and different chamber pressures. Outside the parent gas, both CF3 and CF4 were found under all operating conditions. CF3I density decreases monotonically with increasing plasma power. In comparison, CF3 densities peaked at moderate plasma powers (200 W), while CF4 densities increased with power. Above 300 W, small levels of C2F6 were also observed. At high powers, a large fraction of gas phase chemistry is not observable via FTIR spectrometry, suggesting the presence of significant quantities of I, I2, F, and F2. A greater understanding of CF3I could yield better methods for large scale semiconductor etching and help to add clarity to the creation of CxFy species.
Acoustic-intensity striations below the critical depth: Interpretation and modeling
Authors: Duan Rui , Yang Kunde , Li Hui , Ma Yuanliang
Published: September 2017

This paper presents a technique for calculating tracks of striations observed in the plot of acoustic intensity versus range and frequency. The striations result from the interference in acoustic propagation below the critical depth. The key of this technique is modeling Lloyd's-mirror interference fringes based on the ray-based description of the normal modes. Then, as the striations are interpreted as sampling fringes at different frequencies and ranges, a method to calculate their tracks is proposed based on the fringe model. Finally, experimental observations of striations are compared with results from the presented technique.
Glia put visual map in sync
Authors: Isaacman-Beck Jesse , Clandinin Thomas R.
Published: August 2017

Sequential intercellular signals synchronize neuronal differentiation to assemble a visual map
The architecture of transcription elongation
Authors: Fouqueau Thomas , Werner Finn
Published: August 2017

A crystal structure explains how transcription factors enhance elongation and pausing
Corrected Genome Sequence of Acinetobacter baumannii Strain AB0057, an Antibiotic-Resistant Isolate from Lineage 1 of Global Clone 1
Authors: Hamidian Mohammad , Venepally Pratap , Hall Ruth M. , Adams Mark D.
Published: September 2017

Extensively antibiotic-resistant
Acinetobacter baumannii
isolate AB0057 recovered in the United States in 2004 was one of the first global clone 1 isolates to be completely sequenced. Here, the complete 4.05-Mb genome sequence (chromosome and one plasmid) has been revised using Illumina HiSeq data and targeted sequencing of PCR products.
A worldwide survey of retinopathy of prematurity screening
Authors: Mora Justin S , Waite Christopher , Gilbert Clare E , Breidenstein Brenda , Sloper John J
Published: August 2017

Background

To ascertain which countries in the world have retinopathy of prematurity (ROP) screening programmes and guidelines and how these were developed.

Methods

An email database was created and requests were sent to ophthalmologists in 141 nations to complete an online survey on ROP screening in their country.

Results

Representatives from 92/141 (65%) countries responded. 78/92 (85%) have existing ROP screening programmes, and 68/78 (88%) have defined screening criteria. Some countries have limited screening and those areas which have no screening or for which there is inadequate knowledge are mainly Southeast Asia, Africa and some former Soviet states.

Discussion

With the increasing survival of premature babies in lower-middle-income and low-income countries, it is important to ensure that adequate ROP screening and treatment is in place. This information will help organisations focus their resources on those areas most in need.
Is cardiovascular risk reduction therapy effective in South Asian, Chinese and other patients with diabetes? A population-based cohort study from Canada
Authors: Ke Calvin H , Morgan Steve , Smolina Kate , Gasevic Danijela , Qian Hong , Khan Nadia A
Published: September 2017

Objectives

Guidelines recommend ACE inhibitors (ACEi), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs) and diuretics in all patients with diabetes mellitus. However, the effectiveness of these agents in South Asian and Chinese populations is unknown. We sought to determine whether ACEi, ARB, CCB and diuretics are associated with reduced mortality in South Asian, Chinese and other patients with diabetes.

Design

Population-based cohort study using administrative health databases.

Setting

Province of British Columbia, Canada (2006–2013).

Participants

Patients aged ≥35 years with incident diabetes.

Primary and secondary outcome measures

Primary outcome was all-cause mortality for each medication class compared with untreated patients within each ethnicity. Treatment effect was assessed using inverse probability of treatment weighted Cox proportional hazards models. Medication adherence effect on mortality was also evaluated.

Results

208 870 patients (13 755 South Asian, 22 871 Chinese, 172 244 other Canadian) were included. ACEi reduced mortality in other patients (HR=0.88, 0.84–0.91), but power was insufficient to evaluate for benefit in Chinese and South Asian patients. ARB and diuretics reduced mortality in Chinese (ARB HR=0.64, 0.50–0.82; diuretics HR=0.77, 0.62–0.96) and other patients (ARB HR=0.69, 0.64–0.74; diuretics HR=0.66, 0.63–0.69) compared with untreated patients. No mortality benefit was observed among South Asians for any drug class or for CCB among all ethnicities. Higher medication adherence was associated with lower mortality for other patients only (HR=0.79, 0.72–0.86).

Conclusions

Effectiveness of cardiovascular risk reduction therapy on mortality varies considerably by ethnicity. Further study is needed to evaluate the mortality benefit of antihypertensive agents in South Asians. Inclusion of these ethnic groups in future clinical trials is essential to examine for differential responses.
Mental health impacts of flooding: a controlled interrupted time series analysis of prescribing data in England
Authors: Milojevic Ai , Armstrong Ben , Wilkinson Paul
Published: September 2017

Background

There is emerging evidence that people affected by flooding suffer adverse impacts on their mental well-being, mostly based on self-reports.

Methods

We examined prescription records for drugs used in the management of common mental disorder among primary care practices located in the vicinity of recent large flood events in England, 2011–2014. A controlled interrupted time series analysis was conducted of the number of prescribing items for antidepressant drugs in the year before and after the flood onset. Pre–post changes were compared by distance of the practice from the inundated boundaries among 930 practices located within 10 km of a flood.

Results

After control for deprivation and population density, there was an increase of 0.59% (95% CI 0.24 to 0.94) prescriptions in the postflood year among practices located within 1 km of a flood over and above the change observed in the furthest distance band. The increase was greater in more deprived areas.

Conclusions

This study suggests an increase in prescribed antidepressant drugs in the year after flooding in primary care practices close to recent major floods in England. The degree to which the increase is actually concentrated in those flooded can only be determined by more detailed linkage studies.
Resilience: not just a brave face
Authors: Sullivan Gemma , Gregson Christine
Published: August 2017

This article provides a review of the 2017 Faculty of Medical Leadership and Management Conference in Scotland with reflections on the promotion of personal, managerial and organisational resilience.
Growth and interaction of normal faults and fault network evolution in rifts: insights from three-dimensional discrete element modelling
Authors: Finch Emma , Gawthorpe Rob
Published: August 2017

The initiation, growth and interaction of faults within an extensional rift is an inherently four-dimensional process where connectivity with time and depth are difficult to constrain. A 3D discrete element model is employed that represents the crust as a two-layered brittle–ductile system in which faults nucleate, propagate and interact in response to local heterogeneities and resulting stresses. Faults nucleate in conjugate sets throughout the model brittle crust; they grow through a combination of tip propagation and interaction of co-linear segments to form larger normal faults. Segment linkage occurs by merging of adjacent fault segments located along strike, downdip or oblique to one another. Finally, deformation localizes onto the largest faults. Displacement distribution on faults is highly variable with marked along-strike and temporal variations in displacement rates. Displacement maxima continuously migrate as smaller fault segments interact and link to form the final fault plane. As a result, displacement maxima associated with fault nucleation sites are not coincident with the location of the maximum finite displacement on a fault where segment linkage overprints the record. The observed style of fault growth is consistent with the isolated growth model in the earliest stages which then gives way to a coherent (constant-length) fault growth model at greater strains.
Toward Real-Time Ray Tracing
Authors: Deng Yangdong , Ni Yufei , Li Zonghui , Mu Shuai , Zhang Wenjun
Published: September 2017

Ray tracing has long been considered as the next-generation technology for graphics rendering. Recently, there has been strong momentum to adopt ray tracing--based rendering techniques on consumer-level platforms due to the inability of further enhancing user experience by increasing display resolution. On the other hand, the computing workload of ray tracing is still overwhelming. A 10-fold performance gap has to be narrowed for real-time applications, even on the latest graphics processing units (GPUs). As a result, hardware acceleration techniques are critical to delivering a satisfying level performance while at the same time meeting an acceptable power budget. A large body of research on ray-tracing hardware has been proposed over the past decade. This article is aimed at providing a timely survey on hardware techniques to accelerate the ray-tracing algorithm. First, a quantitative profiling on the ray-tracing workload is presented. We then review hardware techniques for the main functional blocks in a ray-tracing pipeline. On such a basis, the ray-tracing microarchitectures for both ASIC and processors are surveyed by following a systematic taxonomy.
A Survey of Algorithmic Debugging
Authors: Caballero Rafael , Riesco Adrián , Silva Josep
Published: September 2017

Algorithmic debugging is a technique proposed in 1982 by E. Y. Shapiro in the context of logic programming. This survey shows how the initial ideas have been developed to become a widespread debugging schema fitting many different programming paradigms and with applications out of the program debugging field. We describe the general framework and the main issues related to the implementations in different programming paradigms and discuss several proposed improvements and optimizations. We also review the main algorithmic debugger tools that have been implemented so far and compare their features. From this comparison, we elaborate a summary of desirable characteristics that should be considered when implementing future algorithmic debuggers.
Influence of nutrient ingestion on amino acid transporters and protein synthesis in human skeletal muscle after sprint exercise
Authors: Rundqvist Håkan C. , Esbjörnsson Mona , Rooyackers Olav , Österlund Ted , Moberg Marcus , Apro William , Blomstrand Eva , Jansson Eva
Published: September 2017

Nutrient ingestion is known to increase the exercise-induced stimulation of muscle protein synthesis following resistance exercise. Less is known about the effect of nutrients on muscle protein synthesis following sprint exercise. At two occasions separated by 1 mo, 12 healthy subjects performed three 30-s sprints with 20-min rest between bouts. In randomized order, they consumed a drink with essential amino acids and maltodextrin (nutrient) or flavored water (placebo). Muscle biopsies were obtained 80 and 200 min after the last sprint, and blood samples were taken repeatedly during the experiment. Fractional synthetic rate (FSR) was measured by continuous infusion of l-[2H5]phenylalanine up to 200 min postexercise. The mRNA expression and protein expression of SNAT2 were both 1.4-fold higher ( P < 0.05) after nutrient intake compared with placebo at 200 min postexercise. Phosphorylated Akt, mammalian target of rapamycin (mTOR), and p70S6k were 1.7- to 3.6-fold higher ( P < 0.01) 80 min after the last sprint with nutrient ingestion as compared with placebo. In addition, FSR was higher ( P < 0.05) with nutrients when plasma phenylalanine (FSRplasma) was used as a precursor but not when intracellular phenylalanine (FSRmuscle) was used. Significant correlations were also found between FSRplasma on the one hand and plasma leucine and serum insulin on the other hand in the nutrient condition. The results show that nutrient ingestion induces the expression of the amino acid transporter SNAT2 stimulates Akt/mTOR signaling and most likely the rate of muscle protein synthesis following sprint exercise.

NEW & NOTEWORTHY There is limited knowledge regarding the effect of nutrients on muscle protein synthesis following sprint as compared with resistance exercise. The results demonstrate that nutrient ingestion during repeated 30-s bouts of sprint exercise induces expression of the amino acid transporter SNAT2 and stimulates Akt/mTOR signaling and most likely the rate of muscle protein synthesis. Future studies to explore the chronic effects of nutritional ingestion during sprint exercise sessions on muscle mass accretion are warranted.
Immuno-oncology Trial Endpoints: Capturing Clinically Meaningful Activity
Authors: Anagnostou Valsamo , Yarchoan Mark , Hansen Aaron R. , Wang Hao , Verde Franco , Sharon Elad , Collyar Deborah , Chow Laura Q.M. , Forde Patrick M.
Published: September 2017

Immuno-oncology (I-O) has required a shift in the established paradigm of toxicity and response assessment in clinical research. The design and interpretation of cancer clinical trials has been primarily driven by conventional toxicity and efficacy patterns observed with chemotherapy and targeted agents, which are insufficient to fully inform clinical trial design and guide therapeutic decisions in I-O. Responses to immune-targeted agents follow nonlinear dose–response and dose–toxicity kinetics mandating the development of novel response evaluation criteria. Biomarker-driven surrogate endpoints may better capture the mechanism of action and biological response to I-O agents and could be incorporated prospectively in early-phase I-O clinical trials. While overall survival remains the gold standard for evaluation of clinical efficacy of I-O agents in late-phase clinical trials, exploration of potential novel surrogate endpoints such as objective response rate and milestone survival is to be encouraged. Patient-reported outcomes should also be assessed to help redefine endpoints for I-O clinical trials and drive more efficient drug development. This paper discusses endpoints used in I-O trials to date and potential optimal endpoints for future early- and late-phase clinical development of I-O therapies. Clin Cancer Res; 23(17); 4959–69. ©2017 AACR.

See all articles in this CCR Focus section, “Clinical Trial Design Considerations in the Immuno-oncology Era.”
Spotlight on Ibrutinib in PCNSL: Adding Another Feather to Its Cap
Authors: Lakshmanan Aparna , Byrd John C.
Published: September 2017

Summary: In this issue Grommes and colleagues elegantly show that the irreversible inhibitor of Bruton tyrosine kinase, ibrutinib, promotes a high proportion of durable responses in primary central nervous system lymphoma, a type of diffuse large B-cell lymphoma (DLBCL), and also in secondary DLBCL relapsing to the central nervous system. Mutations in the B-cell antigen receptor–associated protein CD79B with upregulation of the MTOR pathway were associated with diminished response, but preclinical combination of PIK3CA and PIK3CD inhibitors synergized with ibrutinib to overcome this resistance mechanism, providing opportunity for further targeted therapy of this difficult-to-treat disease. Cancer Discov; 7(9); 940–2. ©2017 AACR.

See related article by Grommes et al., p. 1018.
SAVE-AMD: Safety of VEGF Inhibitors in Age-Related Macular Degeneration
Authors: Enseleit Frank , Michels Stephan , Sudano Isabella , Stahel Marc , Zweifel Sandrine , Schlager Oliver , Becker Matthias , Winnik Stephan , Nägele Matthias , Flammer Andreas J. , Neidhart Michel , Graf Nicole , Matter Christian M. , Seifert Burkhardt , Lüscher Thomas F. , Ruschitzka Frank
Published: September 2017

Objective: To determine whether intraocular treatment with vascular endothelial growth factor (VEGF) inhibitors change systemic endothelial function (EF) in patients with neovascular age-related macular degeneration (AMD). Methods: In this prospective, randomized, 2-center, double-masked controlled interventional trial, patients with neovascular and dry AMD were enrolled. Eligible neovascular AMD patients received 2 intravitreal loading doses of either ranibizumab 0.5 mg or bevacizumab 1.25 mg at 4-week intervals and were subsequently followed every 4 weeks and treated according to a pro re nata regime for up to 1 year. Patients with dry AMD served as controls. The primary endpoint was the change in EF assessed by flow-mediated dilatation (FMD) after 2 months of treatment with VEGF inhibitors in patients with AMD compared to patients with dry AMD. FMD was assessed with B-mode high-resolution ultrasonography of the left brachial artery. Results: 24 patients with neovascular AMD and 26 patients with dry ADM were included in the trial. Treatment with VEGF inhibitors did not significantly change FMD (from 4.7 ± 2.4 to 3.9 ± 1.9% after 8 weeks, p = 0.07, and to 5.1 ± 2.0% after 1 year; p = 0.93 vs. baseline, respectively). Conclusions: EF did not significantly differ between patients with neovascular AMD treated with intravitreal VEGF inhibition and patients with dry AMD.
Pretreatment Serum Carbohydrate Antigen 19-9 Concentration Is a Predictor of Survival of Patients Who Have Undergone Curative Resection of Stage IV Rectal Cancer
Authors: Miki Hisanori , Akiyoshi Takashi , Ogura Atsushi , Nagasaki Toshiya , Konishi Tsuyoshi , Fujimoto Yoshiya , Nagayama Satoshi , Noma Hisashi , Saiura Akio , Fukunaga Yosuke , Ueno Masashi
Published: August 2017

Background: To evaluate whether pretreatment carcinoembryonic antigen and carbohydrate antigen (CA)19-9 are useful predictors of survival in patients with stage IV rectal cancer who have undergone curative resection. Methods: In this retrospective study, data on 73 patients who had undergone curative resection of stage IV rectal cancer were reviewed. Associations between various clinicopathological factors and survival outcomes were analyzed. Results: According to univariate analysis, elevated pretreatment CA19-9 (p = 0.0028), R1 resection (p = 0.0318), and mucinous or poorly differentiated adenocarcinoma (p = 0.0228) were significantly associated with poor overall survival (OS), and lymph node metastasis (p = 0.0211) was significantly associated with poor disease-free survival (DFS). Multivariate analyses showed that elevated pretreatment serum CA19-9 concentration (hazard ratios [HR] 3.33; 95% CI 1.24-9.42; p = 0.0174) was an independent predictor for OS and lymph node metastasis (HR 2.26; 95% CI 1.15-4.82; p = 0.0164) was an independent predictor for DFS. Among 55 patients with recurrences after curative resection, the rate of complete resection of recurrences was significantly higher in patients with normal pretreatment CA19-9 than in those with elevated CA19-9 (p = 0.049). Post-recurrence survival was significantly worse in patients with elevated pretreatment CA19-9 than in those with normal CA19-9 (p = 0.0196). Conclusions: Pretreatment CA19-9 is good predictor of survival after curative resection of stage IV rectal cancer.
Emerging Roles of Kisspeptin in Sexual and Emotional Brain Processing
Authors: Comninos Alexander N. , Dhillo Waljit S.
Published: August 2017

The emergence of kisspeptin as a crucial regulator of the hypothalamo-pituitary-gonadal (HPG) axis over the last 14 years has answered many questions as to the control of reproductive hormone secretion from the hypothalamus. More recently, the role of kisspeptin outside the HPG axis has received increasing attention in the hope of delineating the pathways linking various sensory and social behaviours to reproduction. These studies, in a range of species from zebrafish to humans, have identified a role for kisspeptin in behavioural networks related to reproduction including olfaction, audition, fear, anxiety, mood, and sexual arousal. The available evidence suggests that extrahypothalamic kisspeptin signalling encourages positive aspects of emotional and sexual brain processing in a presumed drive towards reproduction and ultimately maintenance of the species at a population level. In this review, we examine these studies, which collectively propose that kisspeptin may integrate sexual and emotional brain processing with the control of the HPG axis.
Cidadania comunicativa e midiatização na recepção de cinema com debate
Authors: Pires Maytê Ramos
Published: August 2017

O presente artigo visa refletir sobre a inter ‑relação das mídias no cotidiano dos sujei‑ tos com uma cidadania, em específico na recepção de cinema em sessões comentadas, a partir da construção desenvolvida para uma pesquisa de Mestrado em Ciências da Comunicação. Para tanto, ele trata do contexto de Porto Alegre através de lugares que ofertam esse tipo de sessões promovendo debates, tendo como foco mais con‑ cretamente/aprofundadamente em problematizações acerca de midiatização cine‑ matográfica e de cidadania comunicativa cinematográfica na recepção de sessões de cinema seguidas de debate.
Immunophenotyping of leukocytes in bovine placenta
Authors: Chucri Thais Martins , Monteiro Janaína , Lima Ana Rita De , Bastos Paula Andrea De Santis , Souza Vanessa Aparecida Feijó de , Júnior José Roberto Kfoury
Published: August 2017

Linfócitos e macrófagos são os principais leucócitos envolvidos na tolerância materno-fetal. Pouco se sabe sobre esses leucócitos na placenta bovina, como por exemplo, a quantidade e localização dessas células. Assim, o objetivo desse estudo foi identificar populações de linfócitos e macrófagos na placenta bovina utilizando marcadores específicos e citometria de fluxo. Este estudo analisou amostras de placentônios da região intercaruncular de bovinos nos três trimestres da gestação. No primeiro trimestre, nos placentônios, a porcentagem média de células CD3+ foi 2,34%; CD8+, 1,28%; CD14+, 1,66%; e CD335+, 0,96%. Na região intercaruncular, a porcentagem de células CD3+ foi 0,71%; CD8+, 1,63%; CD14+, 2,81%; e CD335+, 2,81%. No segundo trimestre, os placentonios apresentaram 0,94% de células CD3+; 0,77% de CD8+; 0,72% de CD14+e 0,51% de CD335+. Na região intercaruncular, a porcentagem de células CD3+ foi 0,50%; CD8+, 1,81%; CD14+, 2,64%; e CD335+, 0,51%. No terceiro trimestre, os placentônios apresentaram 0,88% de células marcadas CD3+; 0,66% de CD8+; 1,06% de CD14+ e 0,74% de CD335+. Na região intercaruncular, a porcentagem de células CD3+ foi 0,19%; CD8+, 2,23%; CD14+, 2,43% e CD335+, 0,16%. Os resultados mostraram que a imunomarcação de leucócitos na região do placentônio foi maior do que na região intercaruncular no terceiro trimestre. Concluiu-se que a população de leucócitos CD3+ e CD335+ na placenta bovina está reduzida, provavelmente devido a sua característica sindesmocorial. Essa característica representa uma barreira significante para o sistema imunológico da mãe, o que diminui drasticamente a exposição do concepto ao sistema de defesa da mãe.
Elementos da fiscalidade de Minas Gerais provincial
Authors: Restitutti Cristiano Corte
Published: September 2017

Este artigo trata das transformações da fiscalidade colonial de Minas Gerais na formação do Estado do Brasil. Os sistemas fiscais das províncias foram construídos em ritmos diferenciados. O caso de Minas Gerais apresenta condições específicas, devido à estrutura elaborada e severa da fiscalidade colonial. Destarte, trata-se da inserção de Minas na territorialidade do Império, abrindo seus caminhos secularmente fechados pela política metropolitana. Analisamos o caso de Minas Gerais a partir da evolução de dois tributos: os dízimos e os direitos de entrada. Estes impostos coloniais foram arrecadados em Minas Gerais com poucas modificações até c.1840. Os dízimos transmutaram-se em taxas de exportação em quase todo o Brasil durante a década de 1820, mas em Minas Gerais a transição foi tardia. Os direitos de entrada foram considerados privativos da esfera fiscal imperial, porém foram reeditados em Minas Gerais Provincial através de modalidades de taxas de barreira. A consolidação destes títulos de receita no sistema fiscal de Minas Gerais conflitou com a esfera fiscal geral e com as de outras províncias.
“O que você diz de toda a minha falácia está errado”: sobre o determinismo tecnológico
Authors: Peters John Durham
Published: September 2017

The essay reflects on the so-called technological determinism, discussing it as a “fallacy” and a pejorative word used by academics to criticize their opponents. It shows the intellectual origins of the concept and its developments, concluding that, at the present time, continuing the denunciation of technological determinism is to risk committing a more serious error than giving agency to devices – or to give up criticism. At a time when the meaning of technology is undoubtedly one of the most essential issues facing humanity, it is important to question technology and its historical role. This theme is particularly important for the field of media studies, because if careful explanations of the decisive role of technological mediation are discarded, the raison d’être of the field is impaired.
O poder dos discursos do patronato portuense nas sessões comemorativas de aniversários: rituais verbais, argumentação e configuração enunciativa
Authors: Almeida Carla Aurélia
Published: August 2017

Tendo por base um corpus de notícias com os discursos de aniversário da Associação Industrial Portuense publicados na revista A Indústria do Norte (1949-1970), procederemos à análise do modo como, nestes discursos, se estrutura uma imagem do locutor. Para o efeito, consideramos a organização enunciativa do discurso comemorativo de aniversário, as sequências de atos de discurso e as estratégias discursivas de intensificação e de mitigação ao serviço da persuasão. Verificaremos que os representantes dos patrões põem em jogo um dispositivo argumentativo de convocação de uma doxa partilhada pela comunidade de discurso. Esta estratégia de argumentação é reveladora de uma tomada de posição específica de um locutor representativo do patronato portuense.
Apresentação do Dossiê Artífices da correspondência
Authors: Moraes Marcos Antonio De , Neves Rodrigo Jorge Ribeiro
Published: September 2017

O Dossiê Artífices da correspondência, na Revista do Instituto de Estudos Brasileiros, pretende apresentar artigos representativos das diversas visadas teóricas, metodológicas e hermenêuticas na pesquisa devotada à prática da edição de correspondência e de suas possibilidades de interpretação em clave crítica.
Um espelho invertido da República: a correspondência dos diplomatas franceses no Brasil como objeto histórico (1892-1910)
Authors: Almeida Sílvia Capanema de
Published: September 2017

O artigo apresenta resultados do projeto de pesquisa sobre a correspondência diplomática dos franceses no Brasil na Primeira República. Explora-se um campo novo na história das relações internacionais, que são também nutridas pelos imaginários e trocas sociais, abordando a correspondência dos diplomatas como fonte de pesquisa e como objeto de estudo. Analisam-se dois elementos presentes na documentação: a polêmica sobre a autorização da emigração francesa para o Brasil entre 1875 e 1908 e a imagem da organização política brasileira na virada do século XIX para o XX. A República é vista através de um espelho invertido e forjado pelos ministros plenipotenciários ou cônsules franceses, que são também atores sociais plenos, com objetivos, estilos de escrita, opiniões e finalidades próprios. A Primeira República brasileira é compreendida como uma construção e uma representação ultrapassando as fronteiras nacionais.
As cartas de Osman Lins e Hermilo Borba Filho: uma amizade virtual, tocada pelo real
Authors: Barbosa Nelson Luís
Published: September 2017

Os conterrâneos Osman Lins e Hermilo Borba Filho mantiveram  constante e densa correspondência epistolar, entre 1965 e 1976, interrompida pela morte precoce de Hermilo. Tratavam com  exclusividade de seus projetos de livros, romances, peças teatrais, e de dificuldades relacionadas com o mundo editorial, questões mais  prementes em relação a literatura e escrita e a problemas do país de sua época, sob uma ditadura militar que duraria mais de 20 anos.  Vivendo Hermilo no Recife e Osman em São Paulo, nas poucas vezes em que se encontravam pessoalmente, os assuntos de modo geral resvalavam para questões familiares, cotidianas etc. Assim, o espaço das cartas constituiu o universo virtual privilegiado para essa troca de experiências literárias e de escrita criativa, confirmando que as correspondências de escritores se constituem em verdadeiros arquivos de criação e canteiros de elaboração literária criativa.
“Mário de Andrade da Câmara Cascudo”
Authors: Moraes Marcos Antonio De
Published: September 2017

No arquivo de um escritor, verifica-se, frequentemente, o nomadismo das cartas. A longa missiva do folclorista norte-rio-grandense Luís da Câmara Cascudo (1898-1986) a Mário de Andrade, em 5 de julho de 1929, partilhando o seu conhecimento acerca “de um resto de romance que se cantava no Boi”, deixou de ser guardada pelo destinatário nas pastas de sua correspondência, mas foi inserida entre os papéis que vinha amealhando para a elaboração de um extenso estudo sobre o folclore musical brasileiro, Na pancada do Ganzá.
“necessariamente ‘musicada’”
Authors: Camilotti Virginia
Published: September 2017

As cartas que aqui se transcrevem, subscritas por Mário de Andrade, escritas e remetidas a menos de dois meses de seu falecimento em 25 de fevereiro de 1945, destinaram-se a João Chiarini (1917-1988), ele também, contumaz estudioso das tradições populares brasileiras, sobretudo musicais.
Eulálio Motta: um panfletário no sertão da Bahia
Authors: Barreiros Patrício Nunes
Published: September 2017

O objetivo deste artigo é apresentar a ação panfletária de Eulálio Motta, destacando a produção, circulação e recepção de panfletos no sertão da Bahia. Apesar de sua ação panfletária ter se estendido por mais de 60 anos, o acervo do escritor contém apenas 57 desses impressos. Esses textos revelam importantes características da história cultural das práticas de escrita e de leitura do sertão baiano, envolvendo a ação do panfletário e suas relações com os donos de tipografias e autoridades políticas. A correspondência de Eulálio Motta, seus diários, manuscritos, datiloscritos, dentre outros documentos, são utilizados como fontes para compreender a sua ação panfletária
Regulation of Macrophage Apoptosis and Atherosclerosis by Lipid-Induced PKCδ Isoform Activation
Authors: Li Qian , Park Kyoungmin , Xia Yu , Matsumoto Motonobu , Qi Weier , Fu Jialin , Yokomizo Hisashi , Khamaisi Mogher , Wang Xuanchun , Rask-Madsen Christian , King George L.
Published: August 2017

Rationale:

Activation of monocytes/macrophages by hyperlipidemia associated with diabetes mellitus and obesity contributes to the development of atherosclerosis. PKCδ (protein kinase C δ) expression and activity in monocytes were increased by hyperlipidemia and diabetes mellitus with unknown consequences to atherosclerosis.

Objective:

To investigate the effect of PKCδ activation in macrophages on the severity of atherosclerosis.

Methods and Results:

PKCδ expression and activity were increased in Zucker diabetic rats. Mice with selective deletion of PKCδ in macrophages were generated by breeding PKCδ flox/flox mice with LyzM-Cre and ApoE
−/
−
mice (MPKCδKO/ApoE
−/−
mice) and studied in atherogenic (AD) and high-fat diet (HFD). Mice fed AD and HFD exhibited hyperlipidemia, but only HFD-fed mice had insulin resistance and mild diabetes mellitus. Surprisingly, MPKCδKO/ApoE
−/−
mice exhibited accelerated aortic atherosclerotic lesions by 2-fold versus ApoE
−/−
mice on AD or HFD. Splenomegaly was observed in MPKCδKO/ApoE
−/−
mice on AD and HFD but not on regular chow. Both the AD or HFD increased macrophage number in aortic plaques and spleen by 1.7- and 2-fold, respectively, in MPKCδKO/ApoE
−/−
versus ApoE
−/−
mice because of decreased apoptosis (62%) and increased proliferation (1.9-fold), and not because of uptake, with parallel increased expressions of inflammatory cytokines. Mechanisms for the increased macrophages in MPKCδKO/ApoE
−/−
were associated with elevated phosphorylation levels of prosurvival cell-signaling proteins, Akt and FoxO3a, with reduction of proapoptotic protein Bim associated with PKCδ induced inhibition of P85/PI3K.

Conclusions:

Accelerated development of atherosclerosis induced by insulin resistance and hyperlipidemia may be partially limited by PKCδ isoform activation in the monocytes, which decreased its number and inflammatory responses in the arterial wall.
Sudden Cardiac Death in Women With Suspected Ischemic Heart Disease, Preserved Ejection Fraction, and No Obstructive Coronary Artery Disease: A Report From the Women's Ischemia Syndrome Evaluation Study
Authors: Mehta Puja K. , Johnson B. Delia , Kenkre Tanya S. , Eteiba Wafia , Sharaf Barry , Pepine Carl J. , Reis Steven E. , Rogers William J. , Kelsey Sheryl F. , Thompson Diane V. , Bittner Vera , Sopko George , Shaw Leslee J. , Bairey Merz C. Noel
Published: September 2017

Background

Sudden cardiac death (
SCD
) is often the first presentation of ischemic heart disease; however, there is limited information on
SCD
among women with and without obstructive coronary artery disease (
CAD
). We evaluated
SCD
incidence in the WISE (Women's Ischemia Syndrome Evaluation) study.

Methods and Results

Overall, 904 women with suspected ischemic heart disease with preserved ejection fraction and core laboratory coronary angiography were followed for outcomes. In case of death, a death certificate and/or a physician or family narrative of the circumstances of death was obtained. A clinical events committee rated all deaths as cardiovascular or noncardiovascular and as
SCD
or non‐
SCD
. In total, 96 women (11%) died over a median of 6 years (maximum: 8 years). Among 65 cardiovascular deaths, 42% were
SCD
. Mortality per 1000 person‐hours increased linearly with
CAD
severity (no
CAD
: 5.8; minimal: 15.9; obstructive: 38.6;
P
<0.0001). However, the proportion of
SCD
was similar across
CAD
severity: 40%, 58%, and 38% for no, minimal, and obstructive
CAD
subgroups, respectively (
P
value not significant). In addition to traditional risk factors (age, diabetes mellitus, smoking), a history of depression (
P
=0.018) and longer corrected QT interval (
P
=0.023) were independent
SCD
predictors in the entire cohort. Corrected QT interval was an independent predictor of
SCD
in women without obstructive
CAD
(
P
=0.033).

Conclusions

SCD
contributes substantially to mortality in women with and without obstructive
CAD
. Corrected QT interval is the single independent
SCD
risk factor in women without obstructive
CAD
. In addition to management of traditional risk factors, these data indicate that further investigation should address mechanistic understanding and interventions targeting depression and corrected QT interval in women.