bluuebunny/crossref_metadata_2025 huggingface dataset:
Missing pieces of the Piezo1/Piezo2 baroreceptor hypothesis: an autonomic perspective
Authors: Stocker Sean D. , Sved Alan F. , Andresen Michael C.
Published: July 2019

Baroreceptors play a pivotal role in the regulation of blood pressure through moment to moment sensing of arterial blood pressure and providing information to the central nervous system to make autonomic adjustments to maintain appropriate tissue perfusion. A recent publication by Zeng and colleagues (Zeng WZ, Marshall KL, Min S, Daou I, Chapleau MW, Abboud FM, Liberles SD, Science 362: 464–467, 2018) suggests the mechanosensitive ion channels Piezo1 and Piezo2 represent the cellular mechanism by which baroreceptor nerve endings sense changes in arterial blood pressure. However, before Piezo1 and Piezo2 are accepted as the sensor of baroreceptors, the question must be asked of what criteria are necessary to establish this and how well the report of Zeng and colleagues (Zeng WZ, Marshall KL, Min S, Daou I, Chapleau MW, Abboud FM, Liberles SD, Science 362: 464–467, 2018) satisfies these criteria. We briefly review baroreceptor function, outline criteria that a putative neuronal sensor of blood pressure must satisfy, and discuss whether the recent findings of Zeng and colleagues suitably meet these criteria. Despite the provocative hypothesis, there are significant concerns regarding the evidence supporting a role of Piezo1/Piezo2 in arterial baroreceptor function.
Frequency-dependent entrainment of striatal fast-spiking interneurons
Authors: Higgs Matthew H. , Wilson Charles J.
Published: July 2019

Striatal fast-spiking interneurons (FSIs) fire in variable-length runs of action potentials at 20–200 spikes/s separated by pauses. In vivo, or with fluctuating applied current, both runs and pauses become briefer and more variable. During runs, spikes are entrained specifically to gamma-frequency components of the input fluctuations. We stimulated parvalbumin-expressing striatal FSIs in mouse brain slices with broadband noise currents added to direct current steps and measured spike entrainment across all frequencies. As the constant current level was increased, FSIs produced longer runs and showed sharper frequency tuning, with best entrainment at the stimulus frequency matching their intrarun firing rate. We separated the contributions of previous spikes from that of the fluctuating stimulus, revealing a strong contribution of previous action potentials to gamma-frequency entrainment. In contrast, after subtraction of the effect inherited from the previous spike, the remaining stimulus contribution to spike generation was less sharply tuned, showing a larger contribution of lower frequencies. The frequency specificity of entrainment within a run was reproduced with a phase resetting model based on experimentally measured phase resetting curves of the same FSIs. In the model, broadly tuned phase entrainment for the first spike in a run evolved into sharply tuned gamma entrainment over the next few spikes. The data and modeling results indicate that for FSIs firing in brief runs and pauses firing within runs is entrained by gamma-frequency components of the input, whereas the onset timing of runs may be sensitive to a wider range of stimulus frequency components.

NEW & NOTEWORTHY Specific types of neurons entrain their spikes to particular oscillation frequencies in their synaptic input. This entrainment is commonly understood in terms of the subthreshold voltage response, but how this translates to spiking is not clear. We show that in striatal fast-spiking interneurons, entrainment to gamma-frequency input depends on rhythmic spike runs and is explained by the phase resetting curve, whereas run initiation can be triggered by a broad range of input frequencies.
Illusory changes in the perceived speed of motion derived from proprioception and touch
Authors: Moscatelli Alessandro , Scotto Cecile R. , Ernst Marc O.
Published: July 2019

In vision, the perceived velocity of a moving stimulus differs depending on whether we pursue it with the eyes or not: A stimulus moving across the retina with the eyes stationary is perceived as being faster compared with a stimulus of the same physical speed that the observer pursues with the eyes, while its retinal motion is zero. This effect is known as the Aubert–Fleischl phenomenon. Here, we describe an analog phenomenon in touch. We asked participants to estimate the speed of a moving stimulus either from tactile motion only (i.e., motion across the skin), while keeping the hand world stationary, or from kinesthesia only by tracking the stimulus with a guided arm movement, such that the tactile motion on the finger was zero (i.e., only finger motion but no movement across the skin). Participants overestimated the velocity of the stimulus determined from tactile motion compared with kinesthesia in analogy with the visual Aubert–Fleischl phenomenon. In two follow-up experiments, we manipulated the stimulus noise by changing the texture of the touched surface. Similarly to the visual phenomenon, this significantly affected the strength of the illusion. This study supports the hypothesis of shared computations for motion processing between vision and touch.

NEW & NOTEWORTHY In vision, the perceived velocity of a moving stimulus is different depending on whether we pursue it with the eyes or not, an effect known as the Aubert–Fleischl phenomenon. We describe an analog phenomenon in touch. We asked participants to estimate the speed of a moving stimulus either from tactile motion or by pursuing it with the hand. Participants overestimated the stimulus velocity measured from tactile motion compared with kinesthesia, in analogy with the visual Aubert–Fleischl phenomenon.
Field potential 1/f activity in the subcallosal cingulate region as a candidate signal for monitoring deep brain stimulation for treatment-resistant depression
Authors: Veerakumar Ashan , Tiruvadi Vineet , Howell Bryan , Waters Allison C. , Crowell Andrea L. , Voytek Bradley , Riva-Posse Patricio , Denison Lydia , Rajendra Justin K. , Edwards Johnathan A. , Bijanki Kelly R. , Choi Ki Sueng , Mayberg Helen S.
Published: July 2019

Subcallosal cingulate cortex deep brain stimulation (SCC-DBS) is an experimental therapy for treatment-resistant depression (TRD). Refinement and optimization of SCC-DBS will benefit from increased study of SCC electrophysiology in context of ongoing high-frequency SCC-DBS therapy. The study objective was a 7-mo observation of frequency-domain 1/ f slope in off-stimulation local field potentials (SCC-LFPs) alongside standardized measurements of depression severity in 4 patients undergoing SCC-DBS. SCC was implanted bilaterally with a combined neurostimulation-LFP recording system. Following a 1-mo off-stimulation postoperative phase with multiple daily recordings, patients received bilateral SCC-DBS therapy (130 Hz, 90 μs) and weekly resting-state SCC-LFP recordings over a 6-mo treatment phase. 1/ f slopes for each time point were estimated via linear regression of log-transformed Welch periodograms. General linear mixed-effects models were constructed to estimate pretreatment sources of 1/ f slope variance, and 95% bootstrap confidence intervals were constructed to estimate treatment phase 1/ f slope association with treatment response (50% decrease in preimplantation symptom severity). Results show the time of recording was a prominent source of pretreatment 1/ f slope variance bilaterally, with increased 1/ f slope magnitude observed during night hours (2300–0659). Increase in right 1/ f slope was observed in the setting of treatment response, with bootstrap analysis supporting this observation in 3 of 4 subjects. We conclude that 1/ f slope can be measured longitudinally in a combined SCC-DBS/LFP recording system and likely conforms to known 1/ f circadian variability. The preliminary evidence of 1/ f slope increase during treatment response suggests a potential utility as a candidate biomarker for ongoing development of adaptive TRD-neuromodulation strategies.

NEW & NOTEWORTHY In four patients with treatment-resistant depression undergoing therapeutic deep brain stimulation (DBS), we present the first longitudinal observations of local field potentials (LFP) from the subcallosal cingulate region outside the postoperative period. Specifically, our results demonstrate that frequency-domain 1/ f activity is measurable in a combined DBS-LFP recording system and that right hemisphere recordings appear sensitive to mood state, thus suggesting a potential readout suitable for consideration in ongoing efforts to develop adaptive DBS delivery systems.
Optimization of Ultrasound-Assisted Extraction of Total Flavonoids fromDendranthema indicumvar. aromaticumby Response Surface Methodology
Authors: Zhong Lijie , Liu Yi , Xiong Bin , Chen Lin , Zhang Yaohua , Li Chao
Published: July 2019

Dendranthema indicumvar.aromaticumis a new species with strong fragrance and is used as a herbal medicine by Chinese folks. The abundant flavonoids play important roles in its pharmacological activities. In this study, an ultrasound-assisted method was used to extract total flavonoids (TF) fromD. indicumvar.aromaticumby response surface methodology. A quadratic model was developed to optimize the extraction conditions, whose accuracy was verified by statistic analysis. Ethanol and acetic acid at the volume ratio of 70% : 2% were selected as the extract solvent. The optimized extraction conditions were as follows: extraction time, 40 min; solid/liquid ratio, 1 : 23 g/mL; and temperature, 60°C. This is the first report of an efficient and easy-operating method for TF extraction fromD. indicumvar.aromaticum. Besides, this study provides reference for future pharmacological research onD. indicumvar.aromaticumand extraction of bioactive components from other herbs.
Association between Elevated Serum Tau Protein Level and Sepsis-Associated Encephalopathy in Patients with Severe Sepsis
Authors: Zhao Teng , Xia Yan , Wang Dawei , Pang Li
Published: July 2019

Sepsis-associated encephalopathy (SAE) is a common complication of sepsis. It is imperative to recognize, diagnose, and effectively manage SAE at the early stages. The aim of this study was to evaluate the potential of using the serum tau protein level in the diagnosis of SAE and the prediction of SAE outcomes. This was a retrospective and observational study. The patients included in this study were diagnosed with severe sepsis or septic shock. The serum tau protein level was measured using a commercial enzyme-linked immunosorbent assay. The association between the level of serum tau protein and SAE was assessed by multiple logistic regression analysis. One hundred nine patients with severe sepsis were enrolled during a period of two years. Of the 109 enrolled patients, 27 developed SAE. The serum tau protein level was significantly higher in the patients with SAE than that of the non-SAE group. The serum tau protein level and the sequential organ failure assessment (SOFA) score were independent factors that were associated with SAE. The combined use of the serum tau protein level with the SOFA score improved the accuracy in distinguishing SAE from non-SAE patients. A cutoff value serum tau protein level of 75.92 pg/mL had 81.1% sensitivity and 86.1% specificity in predicting the 28-day mortality in patients with severe sepsis. We identified a close association between the serum tau protein level with the appearance of SAE in patients with severe sepsis. The serum tau protein level can be useful in the prediction of poor outcomes in patients with sepsis.
Pneumonectomy in a Child with Multilobar Pneumatocele Secondary to Necrotizing Pneumonia: Case Report and Review of the Literature
Authors: Gerdung Christopher A. , Ross B. Catherine , Dicken Bryan J. , Bjornson Candice L.
Published: July 2019

Background. Community-acquired pneumonia (CAP) is common within pediatrics and contributes disproportionately to morbidity and mortality. Necrotizing pneumonia is a well-documented complication of CAP. It is thought to be caused by necrosis and liquefaction of consolidated lung and can result in damage to lung parenchyma, including pneumatocele development. Management of necrotizing pneumonia with pneumatocele may include hospitalization, intensive care unit admission, and lengthy antibiotic courses. Severe cases may need invasive procedures. Case Presentation. We present a case of severe necrotizing pneumonia requiring prolonged venovenous extracorporeal membrane oxygenation (V-V ECMO) with development of persistent pneumatoceles, requiring pneumonectomy while on ECMO support to allow for decannulation and extubation. Conclusions. In critically ill patients with extensive unilateral necrotizing pneumonia with pneumatocele development, surgical intervention can be considered when attempts to wean ventilation have been unsuccessful. This case provides evidence that V-V ECMO and pneumonectomy is a viable salvage therapy in the most critically unwell children.
Study on Energy Consumption Characteristics of Different Tools under Impact Load
Authors: Zhao Fujun , Wang Haifan , Ye Zhouyuan , Liu Yonghong , Li Yu
Published: July 2019

Three different tools for rock breaking were designed and fabricated. Impact crushing tests were conducted on granite samples with an identical impact velocity by using the variable section Split Hopkinson pressure bar (SHPB) test device. In the test, the incident energy, absorbed energy, and cumulative energy values of acoustic emission during the process of rock breaking were collected, and energy utilization efficiency was used as a measure of the energy consumption characteristics for three different tools breaking rock. Experimental results showed that the cruciform tool has the best performance with respect to the energy utilization efficiency, followed by the one‐shaped tool and the spherical tool. The cumulative energy values of the acoustic emission of different tools follow the same regularity.
Research on an Ankle Joint Auxiliary Rehabilitation Robot with a Rigid-Flexible Hybrid Drive Based on a 2-S′PS′ Mechanism
Authors: Wang Caidong , Wang Liangwen , Wang Tuanhui , Li Hongpeng , Du Wenliao , Meng Fannian , Zhang Weiwei
Published: July 2019

An ankle joint auxiliary rehabilitation robot has been developed, which consists of an upper platform, a lower platform, a dorsiflexion/plantar flexion drive system, a varus/valgus drive system, and some connecting parts. The upper platform connects to the lower platform through a ball pin pair and two driving branch chains based on the S′PS′ mechanism. Although the robot has two degrees of freedom (DOF), the upper platform can realize three kinds of motion. To achieve ankle joint auxiliary rehabilitation, the ankle joint of patients on the upper platform makes a bionic motion. The robot uses a centre ball pin pair as the main support to simulate the motion of the ankle joint; the upper platform and the centre ball pin pair construct a mirror image of a patient’s foot and ankle joint, which satisfies the human body physiological characteristics; the driving systems adopt a rigid-flexible hybrid structure; and the dorsiflexion/plantar flexion motion and the varus/valgus motion are decoupled. These structural features can avoid secondary damage to the patient. The rehabilitation process is considered, and energy consumption of the robot is studied. An experimental prototype demonstrates that the robot can simulate the motion of the human foot.
Diagnosis of Prenatal-Onset Achondrogenesis Type II by a Multidisciplinary Assessment: A Retrospective Study of 2 Cases
Authors: Wang Wenbo , Wu Qichang , Sun Li , Zhong Xiaohong , Xu Yasong , Xie Xiaojian , Su Zhiying
Published: July 2019

Aim.Achondrogenesis type II is a rare, lethal osteochondrodysplasia with considerable phenotypic heterogeneity. We describe our experience in diagnosing prenatal-onset achondrogenesis type II by a multidisciplinary assessment.Methods.Two cases of fetal achondrogenesis type II were analyzed retrospectively using prenatal ultrasound evaluation, postnatal radiographic diagnosis, and molecular genetic testing ofCOL2A1.Results.A causative mutation in theCOL2A1gene was found in both patients. Combined with postnatal radiographic examination, the final diagnosis of achondrogenesis type II was made.Conclusion.Our findings emphasize the importance of a multidisciplinary assessment for the definitive diagnosis of achondrogenesis type II, which is paramount for proper genetic counseling.
Ten-Year Follow-Up of Collision Tumors Composed of Craniopharyngioma and Pituitary Adenoma: A Case Report and Literature Review
Authors: Miyazaki Takeshi , Kowari Kentaro , Eda Hirotake , Kambara Mizuki , Maruyama Riruke , Akiyama Yasuhiko
Published: July 2019

Although craniopharyngioma (CP) and pituitary adenoma (PA) are common tumors of the parasellar lesions, the coexistence of CP and PA is very rare. A 48-year-old male visited our hospital because of consciousness disturbance. The neuroimaging revealed a sellar tumor contact with a massive suprasellar cyst including calcification. Preoperative diagnosis was CP, and the patient underwent craniotomy to resolve the suprasellar mass effect. The histological examination disclosed adamantinomatous CP, and subsequently a transsphenoidal approach was chosen for the residual intrasellar tumor. Against expectations, the histological diagnosis was not CP but PA. The patient underwent gamma knife surgery for the residual tumor, and the postoperative course was good. After a 10-year follow-up, both lesions were still completely controlled. If we had suspected and diagnosed the tumor involved as not only CP but also PA at the first operation, the second operation could have been avoided because we would have chosen gamma knife surgery for the residual tumor. We should draw attention to this rare situation for differential diagnosis of parasellar tumor to avoid unnecessary surgery and to decide the best strategy for treatment. In addition, the biological behavior of collision tumors composed of CP and PA is probably the same as solitary CP or PA based on a long-term follow-up of our case.
Touch and Pain Sensations in Diadynamic Current (DD) and Transcutaneous Electrical Nerve Stimulation (TENS): A Randomized Study
Authors: Demidaś Aneta , Zarzycki Mikołaj
Published: July 2019

The study investigated touch and pain sensations and the correlation between them in diadynamic current (DD) and transcutaneous electrical nerve stimulation (TENS), electrotherapies commonly applied in musculoskeletal disorders and occupational rehabilitation medicine. Forty healthy subjects were treated with either DD (n=20) or TENS (n=20). Each treatment consisted of three sessions with one-week interval. Touch sensation was determined with the JVP Domes esthesiometer, pain sensation with pressure pain threshold (PPT), and pressure pain tolerance threshold (PPTO) by an algometer. During each session the measurements were performed before the application of the procedure (T0), immediately after it (T1), and 30 minutes after the end of the procedure (T2). Both DD and TENS increased touch sensation (p<0.01) and did not significantly alter PPT and PPTO (p>0.05). No statistically significant differences in short-term effects, i.e., 3 weeks of the trial, were noted between DD and TENS in their influence on touch and pain sensations (p>0.05). There was a high significant correlation between touch and pain sensations in DD (r=0.86). TENS and DD caused similar analgesic effects. DD, which is shorter in the duration of the treatment, may comprise a realistic alternative to TENS in clinical practice of pain management.
Remote Sensing: An Advanced Technique for Crop Condition Assessment
Authors: Ennouri Karim , Kallel Abdelaziz
Published: July 2019

Actually, cultivators are increasingly arranging innovative high technical and scientific estimations in the aim to enhance agricultural sustainability, effectiveness, and/or plant health. Innovative farming technologies incorporate biology with smart agriculture: computers and devices exchange with one another autonomously in a structured farm management system. Throughout this structure, smart agriculture can be accomplished; cultivators decrease plantation inputs (pesticides and fertilizers) and increase yields via integrated pest management and/or biological control. The emerging concept of remote sensing may provide a framework to systematically consider these issues of smart farming technology and to embed high‐tech agriculture better. The impact(s) may be beneficial depending on how tools, such as data mining, and imagery technologies, such as picture treatment and analysis, are applied. Remote sensing technology is discussed in this review and demonstrates its possibility to create novel opportunities for scientists (and agronomists) to explore aspects of biological phenomena that cannot be accessed through usual mechanisms or processes.
Inferior Oblique Muscle Overaction: Clinical Features and Surgical Management
Authors: Ozsoy Ercan , Gunduz Abuzer , Ozturk Emrah
Published: July 2019

Purpose. To further define the clinical features of patients with inferior oblique muscle overaction (IOOA) and evaluate the surgical results in a subgroup of these patients. Methods. The medical records of 173 patients who underwent inferior oblique muscle (IO) weakening surgery due to primary or secondary IOOA were retrospectively reviewed. The patients were assigned a surgical group based on severity of IOOA and presence of dissociated vertical deviation (DVD) or hypertropia. Patients with +1 or +2 IOOA underwent recession, patients with +3 or +4 IOOA underwent myectomy, and patients with any grade of IOOA and DVD or hypertropia underwent anterior transposition (AT) surgery. Results. A total of 286 eyes of 173 patients who underwent surgery due to IOOA were included in the study. IOOA was accompanied by esotropia, exotropia, abnormal head posture (AHP), pattern strabismus, convergence insufficiency, DVD, facial asymmetry, and nystagmus. The most common comorbid disorder was esotropia. The recession was used in 173 eyes, myectomy in 64, and AT in 49. Surgical success was obtained in 96.0% of eyes that underwent recession, in 98.4% of eyes that underwent myectomy, and in 93.9% of eyes that underwent AT. In the follow-up, IOOA occurred in the fellow eye in 36.1% of patients who underwent unilateral surgery. Conclusions. This study is a comprehensive report on the concomitants of the IOOA. Also, it showed that all of the three surgical procedures including recession, myectomy, and AT are effective in the surgical management of IOOA when performed in select patient groups.
Safety and Efficacy of the C-117 Formula for Vulnerable Carotid Artery Plaques (Spchim): A Randomized Double-Blind Controlled Pilot Study
Authors: Gong Baoying , Chen Xiuyan , Lin Rongming , Zhang Feng , Zhong Jingxin , Zhang Qixin , Zhou Yuexiang , Li Haijun , Zeng Liling , Jiang Zonghua , Guo Jianwen
Published: July 2019

Objective. To investigate the safety and efficacy of the Herbal Medicine C-117 (C-117) formula in the treatment of carotid atherosclerotic vulnerable plaques. Methods. This was a prospective, single-centre, randomized, double-blind study. A total of 120 eligible patients were randomly divided into two groups to receive the C-117 formula or placebo. As the basic treatment, both groups were treated according to the Guidelines for Secondary Prevention of Ischemic Stroke/Transient Ischemic Stroke in China using statins to regulate blood lipids, blood pressure lowering drugs, drugs for controlling blood sugar, and antiplatelet drugs according to the indications. The primary outcomes were the change in stability, the mean change of the plaque Crouse score, and the area and number of bilateral carotid artery plaques before and after 6 months of treatment. The secondary outcomes were the total number of cardiocerebrovascular events during the treatment and follow-up and the mean changes of lipid levels. Result. After 180 days of treatment, the plaque Crouse score(95% CI, 0.39 (0.01-0.77), P=0.046) and plaque area (95% CI, 2.14 (-10.10-14.39), P=0.727) were lower in the C-117 formula group than that before treatment. The plaque Crouse score of the control group (95% CI, 0.17 (-0.24-0.57), P=0.417) was lower than that before treatment, while the plaque area (95% CI, -0.35 (-9.35-8.65), P=0.938) increased, but without statistical significance. There was no significant difference in the reduction of the intima-media thickness (IMT), plaque Crouse score, or plaque area between the two groups after treatment (P>0.05). Subgroup analysis of patients whose Lipitor medication time ≥ 20% of the 6-month treatment showed that the levels of total cholesterol, triglycerides, and low-density lipoprotein were lower in the two groups after treatment than before, and the low-density lipoprotein levels in the C-117 formula group significantly decreased (95% CI, 2.99 (-0.08-0.39), P=0.005), but there was no statistical difference between the two groups after treatment (P>0.05). No serious adverse events occurred in the two groups after 180 days of treatment. Conclusion. The C-117 formula may be antiatherosclerotic by strengthening statins to reduce the low-density lipoprotein levels and reducing the carotid plaque Crouse scores. Clinical trials with large sample sizes, long-term interventions, and follow-up are needed to investigate the efficacy of the C-117 formula. Clinical Trials Registration. This trial is registered with clinicaltrials.gov identifier: NCT03072225 (registered retrospectively on 1st March 2017).
Modeling Gliomas Using Two Recombinases
Authors: Hara Toshiro , Verma Inder M.
Published: July 2019

Development of animal models to investigate the complex ecosystem of malignant gliomas using the Cre/loxP recombination system has significantly contributed to our understanding of the molecular underpinnings of this deadly disease. In these model systems, once the tumor is induced by activation of Cre-recombinase in a tissue-specific manner, further genetic manipulations to explore the progression of tumorigenesis are limited. To expand the application of mouse models for gliomas, we developed glial fibrillary acidic protein (GFAP)-FLP recombinase (FLPo) mice that express FLPo recombinase specifically in GFAP-positive cells. Lentivirus-based in vivo delivery of cancer genes conditioned by FLP/FRT-mediated recombination initiated gliomas in GFAP-FLPo mice. Using the Cre-mediated multifluorescent protein–expressing system, we demonstrated that the GFAP-FLPo mouse model enables the analysis of various stages of gliomagenesis. Collectively, we present a new mouse model that will expand our ability to dissect developmental processes of gliomagenesis and to provide new avenues for therapeutic approaches.

Significance:

This study presents a new glioma mouse model derived using lentiviral vectors and two recombination systems that will expand the ability to dissect developmental processes of gliomagenesis.
A Phenome-Wide Mendelian Randomization Study of Pancreatic Cancer Using Summary Genetic Data
Authors: Langdon Ryan J. , Richmond Rebecca C. , Hemani Gibran , Zheng Jie , Wade Kaitlin H. , Carreras-Torres Robert , Johansson Mattias , Brennan Paul , Wootton Robyn E. , Munafo Marcus R. , Smith George Davey , Relton Caroline L. , Vincent Emma E. , Martin Richard M. , Haycock Philip
Published: July 2019

Background:

The 5-year mortality rate for pancreatic cancer is among the highest of all cancers. Greater understanding of underlying causes could inform population-wide intervention strategies for prevention. Summary genetic data from genome-wide association studies (GWAS) have become available for thousands of phenotypes. These data can be exploited in Mendelian randomization (MR) phenome-wide association studies (PheWAS) to efficiently screen the phenome for potential determinants of disease risk.

Methods:

We conducted an MR-PheWAS of pancreatic cancer using 486 phenotypes, proxied by 9,124 genetic variants, and summary genetic data from a GWAS of pancreatic cancer (7,110 cancer cases, 7,264 controls). ORs and 95% confidence intervals per 1 SD increase in each phenotype were generated.

Results:

We found evidence that previously reported risk factors of body mass index (BMI; 1.46; 1.20–1.78) and hip circumference (1.42; 1.21–1.67) were associated with pancreatic cancer. We also found evidence of novel associations with metabolites that have not previously been implicated in pancreatic cancer: ADpSGEGDFXAEGGGVR*, a fibrinogen-cleavage peptide (1.60; 1.31–1.95), and O-sulfo-l-tyrosine (0.58; 0.46–0.74). An inverse association was also observed with lung adenocarcinoma (0.63; 0.54–0.74).

Conclusions:

Markers of adiposity (BMI and hip circumference) are potential intervention targets for pancreatic cancer prevention. Further clarification of the causal relevance of the fibrinogen-cleavage peptides and O-sulfo-l-tyrosine in pancreatic cancer etiology is required, as is the basis of our observed association with lung adenocarcinoma.

Impact:

For pancreatic cancer, MR-PheWAS can augment existing risk factor knowledge and generate novel hypotheses to investigate.
SLAMF6 as a Regulator of Exhausted CD8+ T Cells in Cancer
Authors: Yigit Burcu , Wang Ninghai , ten Hacken Elisa , Chen Shih-Shih , Bhan Atul K. , Suarez-Fueyo Abel , Katsuyama Eri , Tsokos George C. , Chiorazzi Nicholas , Wu Catherine J. , Burger Jan A. , Herzog Roland W. , Engel Pablo , Terhorst Cox
Published: July 2019

The tumor microenvironment in leukemia and solid tumors induces a shift of activated CD8+ cytotoxic T cells to an exhausted state, characterized by loss of proliferative capacity and impaired immunologic synapse formation. Efficient strategies and targets need to be identified to overcome T-cell exhaustion and further improve overall responses in the clinic. Here, we took advantage of the Eμ-TCL1 chronic lymphocytic leukemia (CLL) and B16 melanoma mouse models to assess the role of the homophilic cell-surface receptor SLAMF6 as an immune-checkpoint regulator. The transfer of SLAMF6+ Eμ-TCL1 cells into SLAMF6−/− recipients, in contrast to wild-type (WT) recipients, significantly induced expansion of a PD-1+ subpopulation among CD3+CD44+CD8+ T cells, which had impaired cytotoxic functions. Conversely, administering anti-SLAMF6 significantly reduced the leukemic burden in Eμ-TCL1 recipient WT mice concomitantly with a loss of PD-1+CD3+CD44+CD8+ T cells with significantly increased effector functions. Anti-SLAMF6 significantly reduced leukemic burden in the peritoneal cavity, a niche where antibody-dependent cellular cytotoxicity (ADCC) is impaired, possibly through activation of CD8+ T cells. Targeting of SLAMF6 affected tumor growth not only in B cell–related leukemia and lymphomas but also in nonhematopoietic tumors such as B16 melanoma, where SLAMF6 is not expressed. In vitro exhausted CD8+ T cells showed increased degranulation when anti-human SLAMF6 was added in culture. Taken together, anti-SLAMF6 both effectively corrected CD8+ T-cell dysfunction and had a direct effect on tumor progression. The outcomes of our studies suggest that targeting SLAMF6 is a potential therapeutic strategy.
Quick Recovery of Renal Alterations and Inflammatory Activation after a Marathon
Authors: Panizo González Nayara , Reque Santivañez Javier Eduardo , Hernando Fuster Barbara , Collado Boira Eladio J. , Martinez-Navarro Ignacio , Chiva Bartoll Óscar , Hernando Domingo Carlos
Published: July 2019

Purpose: We evaluated the incidence of acute kidney injury in a cohort of marathon participants. Methods: We conducted a prospective observational study focused on evaluating the incidence of kidney damage after a marathon, and its evolution in the first 48 h after the marathon in 88 runners who completed the Valencia Marathon. Results: From the 88 participants, 42 (48.28%) presented with acute kidney injury, mainly grade 1 (95.20%). Microscopic haematuria was observed in 29 runners (33%). Levels of interleukin 6, leukocytes, and neutrophils were markedly increased at the marathon’s finish line. Conclusions: Our results confirmed that there are slight transient changes in glomerular filtration rate and inflammatory activation after a marathon.
Assessment of Predictors of Sun Sensitivity as Defined by Fitzpatrick Skin Phototype in an Ecuadorian Population and Its Correlation with Skin Damage
Authors: Falcon Kirsten , Fors Martha , Palacios Alvarez Santiago , Veintimilla Karla , Lasso Nélida , Navas Carlos
Published: July 2019

Background: The Fitzpatrick skin phototype scale (FSPTS) is a widely used instrument to assess skin type. Methods: A cross-sectional survey collected responses from 254 subjects from Quito regarding self-reported FSPTS, gender, age, education, and tobacco and alcohol consumption. Univariate and multivariate logistic regression analyses were performed to determine if ethnicity, hair color, and eye color significantly predict FSPTS. In addition, we studied the correlation between FSPTS and the SCINEXA scale with Pearson’s correlation coefficient. Results: Ethnicity, eye color, and hair color are significant independent predictors of FSPTS (p < 0.0001). Conclusions: Patient self-reported race and pigmentary phenotypes are inaccurate predictors of sun sensitivity as defined by Fitzpatrick skin phototype. Our study does not fully represent the population of the country. There are limitations to using patient-reported race and appearance in predicting individual sunburn risk.
Measurement of Fractional Exhaled Nitric Oxide: Comparison of Three Different Analysers
Authors: Korn Stephanie , Wilk Maike , Voigt Stefanie , Weber Stephan , Keller Thomas , Buhl Roland
Published: July 2019

Background: Fractional exhaled nitric oxide (FeNO) is a surrogate marker for airway inflammation, supporting the diagnostic pathway and treatment decisions for asthma patients. Objectives: Aim of this study was to compare the new analyser Vivatmo pro (Bosch, BV) with NIOX VERO (Circassia, CN) and CLD (Ecomedics, EC). Methods: In 100 asthmatics (median 53 years [range 20–87], 62% female, 86% on inhaled corticosteroids [mean 1,300 μg beclomethasone dipropionate or equivalent], 35% treated with biologics) 2 FeNO measurements per device were performed. Additionally, the success rate to achieve a valid NO value was evaluated. Results: Sixty-eight percent of the patients had FeNO values below 50 ppb. Median NO concentrations were 31 ppb (range 6–194) for BV, 33 ppb (9–164) for CN and 31ppb (7–353) for EC. Bland-Altman plots suggested an agreement within the predefined limits of ±5 ppb for all analysers within the therapeutically relevant range (0–70 ppb). The highest agreement in FeNO levels were between BV and EC with mean differences of –0.26 (95% CI –1.48 to 0.95) vs. 1.52 (95% CI 0.4–2.6) ppb for CN and EC. The results indicate an equivalence of the methods (two-one sided t test-equivalence test: p < 0.0001, ±5 ppb margins). Acceptance of the measurements was high for all devices (97%). The highest success rate to obtain 2 valid NO values without failed attempts was achieved with the BV analyser (73 vs. 62% for the CN analyser and 46% for the EC analyser). Conclusions: For the range between 0 and 70 ppb, FeNO concentrations measured with all 3 devices were statistically equivalent within predefined acceptance criteria and did not differ in a clinically relevant way.
Proteomic Profile of Carbonylated Proteins Screen the Regulation of Calmodulin-Dependent Protein Kinases-AMPK-Beclin1 in Aerobic Exercise-Induced Autophagy in Middle-Aged Rat Hippocampus
Authors: Liu Wenfeng , Xia Yan , Kuang Heyu , Wang Zhiyuan , Liu Shaopeng , Tang Changfa , Yin Dazhong
Published: July 2019

Background: Carbonylation is an oxidative modification of the proteins and a marker of oxidative stress. The accumulation of toxic carbonylated proteins might be one of the onsets of pathogenesis in hippocampal aging or neurodegeneration. Enormous evidence indicates that regular aerobic exercise might alleviate the dysfunction of carbonylated proteins, but the adaptational mechanisms in response to exercise are unclear. Objective: This study explored the carbonyl stress mechanism in the hippocampus using proteomics and the role of calmodulin-dependent protein kinases (CAMK)-AMP-activated protein kinase (AMPK)-Beclin1 signaling pathways in alleviating aging or improving function with regular aerobic exercise. Methods: Twenty-four healthy 13-month-old male Sprague-Dawley rats (average 693.21 ± 68.85 g) were randomly divided into middle-aged sedentary control group (M-SED, n = 12) and middle-aged aerobic exercise runner group (M-EX, n = 12). The M-EX group participated in regular aerobic exercise – treadmill running – with exercise intensity increasing gradually from 50–55% to 65–70% of maximum oxygen consumption (V˙O2max) over 10 weeks. The targeted proteins of oxidative modification were profiled by avidin magnetic beads and electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-Q-TOF-MS). Western blots were used to test for molecular targets. Results: Regular aerobic exercise restores the intersessional habituation and rescues the hippocampus morphological structure in middle-aged rats. ­ESI-Q-TOF-MS screened 56 carbonylated proteins only found in M-SED and 16 carbonylated proteins only found in M-EX, indicating aerobic exercise decreased carbonyl stress. Intriguingly, Ca2+/CAMK II alpha (CAMKIIα) was carbonylated only in the M-SED group at the oxidative modification site of 4-hydroxynonenal adducts, while regular aerobic exercise alleviated CAMKIIα carbonylation. Regular aerobic exercise significantly increased the expression and phosphorylated, active levels of CAMKIIα and AMPKα1. It also upregulated the expression of Beclin1 and microtubule-associated protein1-light chain 3 in the hippocampus. Conclusion: Quantification of CAMKIIα carbonylation may be a potential biomarker of the hippocampal senescence. Additionally, regular aerobic exercise-induced autophagy via the activation of CAMK-AMPK-Beclin1 signaling pathway may mitigate the hippocampal neurodegeneration or pathological changes by alleviating protein carbonylation (carbonyl stress).
Triglyceride Glucose Index Predicting Cardiovascular Mortality in Chinese Initiating Peritoneal Dialysis: A Cohort Study
Authors: Yan Zechen , Yu Dahai , Cai Yamei , Shang Jin , Qin Rui , Xiao Jing , Zhao Bin , Zhao Zhanzheng , Simmons David
Published: July 2019

Background: Insulin resistance (IR) is increased among people with end-stage renal disease (ESRD). The Triglyceride glucose (TyG) index is a marker of IR and is also associated with the prognosis of cardiovascular disease among patients initiating peritoneal dialysis (PD). This study was aimed at examining the associations between TyG index and cardiovascular deaths in patients initiating PD. Methods and Results: Three thousand fifty-four patients initiating PD between 2007 and 2014 were included in a prospective cohort derived from Henan PD Registry, TyG index alongside other baseline characteristics were measured when ESRD patients initiated PD. Logistic regression adjusting for age, gender, and major cardiovascular risk factors estimated the association between TyG index and subsequent cardiovascular mortality within 2 years since the initiation of PD. Results: TyG index was positively associated with cardiovascular mortality: adjusted incidence rates ratio (95% CI) comparing the highest vs. lowest TyG index quartile was 2.32 (2.12–2.55) in all, 2.22 (2.01–2.46) in those with body mass index (BMI) <25 kg/m2, and 2.82 (2.24–3.54) in those with BMI ≥25 kg/m2, respectively. Linear dose-response relationships were revealed in all and by BMI. Conclusions: TyG index might be a prognostic factor in predicting cardiovascular mortality among patients initiating PD.
Ustekinumab with Intravenous Infusion: Results in Hidradenitis Suppurativa
Authors: Romaní Jorge , Vilarrasa Eva , Martorell Antonio , Fuertes Irene , Ciudad Cristina , Molina-Leyva Alejandro
Published: July 2019

Adalimumab is the only approved biological therapy for hidradenitis suppurativa (HS). The last published recommendations support the use of other off-label biologic therapies. We report on a multicentric retrospective review of patients with HS treated with an ustekinumab dosing schedule of intravenous infusion adjusted by weight, followed by a subcutaneous maintenance dose of 90 mg every 8 weeks, as recently approved for Crohn’s disease. The minimal follow-up period required for inclusion was 16 weeks. A total of 14 patients from six hospitals were included. In 50% of the treated patients, therapeutic outcomes, measured by means of the Hidradenitis Suppurativa Clinical Response (HiSCR) and decrease of Dermatology Life Quality Index (DLQI) and visual analog scale (VAS) of pain, were reached at week 16. In 71.42% of patients DLQI and VAS of pain improved, irrespective of achievement of HiSCR. Two patients abandoned treatment due to lack of efficacy or patient preferences. No ustekinumab-related adverse effects were reported. The results are limited by the retrospective nature of the study, the short follow-up period, and the small patient number. This therapeutic regime proved to be safe and showed moderate efficacy in treating HS with failure to previous biologic therapy. Ideally, the efficacy of ustekinumab in HS should be tested in randomized and controlled clinical trials.
The Association of Therapy Adherence and Thyroid Function in Adult Patients with Phenylketonuria
Authors: Sumanszki Csaba , Kiss Erika , Simon Erika , Galgoczi Erika , Soos Aron , Patocs Attila , Kovacs Bela , Nagy Endre V. , Reismann Peter
Published: July 2019

Background: The standard, lifelong therapy of phenylketonuria (PKU) is a natural protein-restricted diet complemented with phenylalanine (Phe)-free L-amino acid mixtures that provide the daily necessary micronutrients. Objective: To assess thyroid function and structure and the iodine status of early-treated adult PKU (ETPKU) patients in Hungary. Methods: Sixty-nine PKU patients (aged 18–41 years) and 50 healthy controls were enrolled in the study. Thyroid hormones, serum thyroglobulin, thyroid antibodies, urinary iodine, and selenium concentrations were measured, and thyroid ultrasound was performed. Results: The incidence of thyroid dysfunction was infrequent (n = 2). Blood Phe was negatively correlated with thyroid-stimulating hormone (TSH), and PKU patients had higher free thyroxine and lower TSH levels than healthy controls. Although optimal iodine status was found in the entire PKU population, by dividing the patients according to their therapy compliance, we observed that lower therapy adherence was associated with mild iodine deficiency and lower urinary selenium levels. Conclusions: The results of this study suggest that iodine status is strongly influenced by the adherence to therapy in ETPKU patients. No or not enough medical food consumption combined with a low-Phe diet can lead to subclinical iodine deficiency.
Small Supernumerary Ring Chromosome Derived from an Inverted Duplication of 13q11.2q14 in a Fetus with Coarctation of the Aorta
Authors: Zeng Jian , Huang Mingyan , Lin Juan , Zhang Xiao , Lan Fenghua
Published: July 2019

Here, we report a molecular characterization of a small supernumerary marker chromosome (sSMC) derived from the most proximal region of 13q present in a fetus with coarctation of the aorta at ultrasound examination during prenatal diagnosis. Cultured umbilical cord blood cells showed a de novo extra ring-shaped sSMC in 76% of the cells using a standard banding technique. SNP array revealed a tetrasomy of about 28.4 Mb in the long arm of chromosome 13 from band 13q11 to 13q14.11 in the fetus's cells. Metaphase/interphase FISH using specific probes located at 13q11, 13q12.11, and 13q14.11, respectively, demonstrated that the supernumerary ring chromosome was derived from an inverted duplication of the region 13q11q14.11 with a conventional centromere. To the best of our knowledge, this is the first time that an inverted duplication of the most proximal region 13q11q14.11 in a ring chromosome is characterized. The findings we presented here deepen our understanding of the clinical consequences of tetrasomy in this region and may be of help for further studies of critical regions in chromosome 13.
Genetic Screening and Personalized Prevention in Colorectal Cancer
Authors: Steinke-Lange Verena , Holinski-Feder Elke
Published: July 2019

Cancer per se is a genetic disease, either originating in germline mutations in cancer genes or in somatic mutations only present in the cancer cells. Therefore, personalized risk prediction, prevention, and treatment for cancer can be based on the results of genetic testing either in the germline or in the tumor. Surveillance regimens need to be based on appropriate risk assessment, which includes germline monogenic genetic testing – where appropriate – and in the future polygenic risk – possibly – for the general population. Treatment regimens should also include germline testing at least for cases suspicious of hereditary tumor diseases, followed by the analysis of somatic mutations within the tumor cell genome, raising a possible target for personalized therapy. Appropriate risk assessment is the key for suitable and, most importantly, individualized surveillance strategies especially in hereditary tumor syndromes. This concerns not only the patient but also the family members at risk. An overview about the different fields and aspects of genetic testing in colorectal cancer and its impact on personalized prevention will be given below.
Evaluation of Serum Glucagon-Like Peptide 1 and Vitamin D Levels in Elderly Patients with Bone Fractures
Authors: Pazarci Özhan , Dogan Halef Okan , Kilinc Seyran , Çamurcu Yalkin
Published: July 2019

Objectives: To evaluate the correlation between levels of serum vitamin D and glucagon-like peptide-1 (GLP-1) in elderly patients with bone fractures. Materials and Methods: This study included 56 patients and 31 control subjects. The patients included were those aged ≥65 years who were admitted to our hospital with a diagnosis of bone fracture. The control group comprised age-matched, healthy individuals. Levels of serum vitamin D and GLP-1 were measured and compared between the 2 groups. Results: Significant differences were noted between the groups in terms of serum levels of vitamin D (p < 0.001) and serum levels of GLP-1 (p < 0.001). A positive correlation was observed between serum levels of vitamin D and GLP-1. Conclusion: Serum levels of GLP-1 were found to be significantly lower in elderly patients with bone fracture compared to healthy adults. In addition, a significant correlation was found between decreased vitamin D and GLP-1 levels. These results may therefore demonstrate the protective effects of GLP-1 on bone structure and metabolism, similar to those of vitamin D.
Metrópoles beduínas
Authors: Kujawski Guilherme
Published: July 2019

A diferença entre práticas habitacionais de povos sedentários e nômades deveria ser analisada mais detidamente pelos estudos de urbanismo. Apesar da condição estática das cidades modernas, a relocalização estrutural tem sido revisitada, em maior escala, não apenas pela arquitetura radical. Mais do que invencionices de artistas, a ideia de avivar cidades, tornado-as elas próprias sujeitos nômades, vem se destacando da fantasia e adquirindo, literalmente, características reais. Apesar de exemplos esparsos, é possível construir uma narrativa que se inicia com imagens procedentes da cultura popular, percorre por projetos de arquitetos visionários da década de 1960 e termina com um caso concreto na Europa do Norte.