bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advanced glycation end-product cross-linking inhibits biomechanical plasticity and characteristic failure morphology of native tendon
Authors: Lee J. Michael , Veres Samuel P. 
Published: January 2019

Advanced glycation end-products (AGEs) are formed in vivo from the nonenzymatic reaction between sugars and proteins. AGEs accumulate in long-lived tissues like tendons, cross-linking neighboring collagen molecules, and are in part complicit in connective tissue pathologies experienced in aging and with diabetes. We have previously described discrete plasticity: a characteristic form of nanoscale collagen fibril damage consisting of serial fibril kinking and collagen denaturation that occurs in some mechanically overloaded tendons. We suspect that this failure mechanism may be an adaptive trait of collagen fibrils and have published evidence that inflammatory cells may be able to recognize and digest the denatured collagen produced by overload. In this study, we treated bovine tail tendons with ribose to simulate long-term AGE cross-linking in vitro. We hypothesized that a high degree of cross-linking would inhibit the intermolecular sliding thought to be necessary for discrete plasticity to occur. Tendons were mechanically overloaded, and properties were investigated by differential scanning calorimetry and scanning election microscopy. Ribose cross-linking treatment altered the mechanical response of tendons after the yield point, significantly decreasing postyield extensibility and strain energy capacity before rupture. Coincident with altered mechanics, ribose cross-linking completely inhibited the discrete plasticity failure mechanism of tendon. Our results suggest that discrete plasticity, which may be an important physiological mechanism, becomes pathologically disabled by the formation of AGE cross-links in aging and diabetes.NEW & NOTEWORTHY We have previously shown that mechanically overloaded collagen fibrils in mammalian tendons accrue nanoscaled damage. This includes development of a characteristic kinking morphology within a shell of denatured collagen: discrete plasticity. Here, using a ribose-incubation model, we show that advanced glycation end-product cross-linking associated with aging and diabetes completely inhibits this mechanism. Since discrete plasticity appears to cue cellular remodeling, this result has important implications for diabetic tendinopathy.
Prestrain and cholinergic receptor-dependent differential recruitment of mechanosensitive energy loss and energy release elements in airway smooth muscle
Authors: Hai Chi-Ming 
Published: January 2019

We tested the hypothesis that oscillatory airway smooth muscle (ASM) mechanics is governed by mechanosensitive energy loss and energy release elements that can be recruited by prestrain and cholinergic stimulation. We measured mechanical energy loss and mechanical energy release in unstimulated and carbachol-stimulated bovine ASM held at prestrains ranging from 0.3 to 1.0 Lo(reference length) and subjected to sinusoidal length oscillation at 1 hz with oscillatory strain amplitudes ranging from 0.1 to 1.5% Lo. We found that oscillatory ASM mechanics during sinusoidal length oscillation is governed predominantly by one class of nonlinear mechanosensitive energy loss element and one class of nonlinear mechanosensitive energy release element with differential mechanosensitivities to oscillatory strain amplitude. The greater mechanosensitivity of the energy loss element than energy release element may explain the bronchodilatory effect of deep inspiration. Prestrain, an important determinant of ASM responsiveness, differentially increased energy loss and energy release in unstimulated and carbachol-stimulated ASM. Cholinergic stimulation, an important cause of bronchoconstriction and airway inflammation, also differentially increased energy loss and energy release. When prestrain and cholinergic stimulation were combined, we found that prestrain and cholinergic stimulation synergistically increased energy loss and energy release by ASM. The relationship between recruitment of energy loss elements and recruitment of energy release elements was nonlinear, suggesting that energy loss and energy release elements are not coupled in ASM cells. These findings imply that large lung volume and cholinergic ASM activation would synergistically increase mechanical energy expenditure during inspiration and mechanical recoil of ASM during expiration.NEW & NOTEWORTHY We report for the first time that oscillatory airway smooth muscle mechanics is governed predominantly by one class of nonlinear mechanosensitive energy loss element and one class of nonlinear mechanosensitive energy release element with differential mechanosensitivities to oscillatory strain amplitude. Prestrain and cholinergic stimulation synergistically and differentially recruit energy loss and energy release elements. The greater mechanosensitivity of the energy loss element than the energy release element may explain the bronchodilatory effect of deep inspiration.
Unfolding the Role of Calreticulin in Myeloproliferative Neoplasm Pathogenesis
Authors: Merlinsky Tiffany R. , Levine Ross L. , Pronier Elodie 
Published: January 2019

Abstract
In 2013, two seminal studies identified gain-of-function mutations in the Calreticulin (CALR) gene in a subset of JAK2/MPL-negative myeloproliferative neoplasm (MPN) patients. CALR is an endoplasmic reticulum (ER) chaperone protein that normally binds misfolded proteins in the ER and prevents their export to the Golgi and had never previously been reported mutated in cancer or to be associated with hematologic disorders. Further investigation determined that mutated CALR is able to achieve oncogenic transformation primarily through constitutive activation of the MPL–JAK–STAT signaling axis. Here we review our current understanding of the role of CALR mutations in MPN pathogenesis and how these insights can lead to innovative therapeutics approaches.
18
F-Sodium Fluoride Imaging of Coronary Atherosclerosis in Ambulatory Patients With Diabetes Mellitus
Authors: Raggi Paolo , Senior Peter , Shahbaz Shima , Kaul Padma , Hung Ryan , Coulden Richard , Yeung Roseanne O. , Abele Jonathan 
Published: January 2019

Objective—
Although patients with diabetes mellitus (DM) are considered at high risk of cardiovascular events, there is growing evidence that this notion is incorrect. Atherosclerosis imaging may identify patients at risk.

Approach and Results—

We performed coronary atherosclerosis with
18
F-sodium fluoride (NaF) positron emission tomography/computed tomography and gated chest computed tomography for coronary artery calcium in 88 consecutive ambulatory patients with DM on a stable medical regimen. NaF has been shown to localize avidly in culprit lesions of patients with acute coronary syndromes and may identify unstable plaques. NaF activity was measured as target (coronary arteries)-to-background (left ventricular pool) ratio (TBR). High TBR was defined as ≥1.5. The mean age of the cohort was 54±14 years, 55% had type 2 DM, 65% were men, the median HgbA1c (hemoglobin A1c) and LDL (low-density lipoprotein) cholesterol were 7.5% (interquartile range, 7.1–8.5) and 1.9 mmol/L (interquartile range, 1.5–2.6), respectively. Mean coronary artery calcium score was 374±773, and median TBR was 1.2. Coronary artery TBR ≥1.5 was detected in 13 (15%) patients. In univariable analyses, male sex (
P
=0.0002), estimated glomerular filtration rate (
P
=0.02), and total coronary artery calcium score (
P
=0.04) were associated with TBR. In multivariable analyses, TBR >median was associated with male sex (
P
=0.0001) and statin use (
P
=0.042).

Conclusions—
In ambulatory patients with DM asymptomatic for cardiovascular disease, the prevalence of potentially vulnerable plaques detected with NaF was low, but in the absence of follow-up data at this stage, we cannot assess the import of this information. Future research will establish whether NaF imaging helps risk stratify patients with DM.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT03530176.
IL (Interleukin)-33 Suppresses Abdominal Aortic Aneurysm by Enhancing Regulatory T-Cell Expansion and Activity
Authors: Li Jingyong , Xia Ni , Wen Shuang , Li Dan , Lu Yuzhi , Gu Muyang , Tang Tingting , Jiao Jiao , Lv Bingjie , Nie Shaofang , Liao Mengyang , Liao Yuhua , Yang Xiangping , Hu Yu , Shi Guo-Ping , Cheng Xiang 
Published: January 2019

Objective—
Inflammation occurs during the progression of abdominal aortic aneurysm (AAA). IL (interleukin)-33 is a pleiotropic cytokine with multiple immunomodulatory effects, yet its role in AAA remains unknown.

Approach and Results—

Immunoblot, immunohistochemistry, and immunofluorescent staining revealed increased IL-33 expression in adventitia fibroblasts from mouse AAA lesions. Daily intraperitoneal administration of recombinant IL-33 or transgenic IL-33 expression ameliorated periaorta CaPO
4
injury- and aortic elastase exposure–induced AAA in mice, as demonstrated by blunted aortic expansion, reduced aortic wall elastica fragmentation, enhanced AAA lesion collagen deposition, attenuated T-cell and macrophage infiltration, reduced inflammatory cytokine production, skewed M2 macrophage polarization, and reduced lesion MMP (matrix metalloproteinase) expression and cell apoptosis. Flow cytometry analysis, immunostaining, and immunoblot analysis showed that exogenous IL-33 increased CD4
+
Foxp3
+
regulatory T cells in spleens, blood, and aortas in periaorta CaPO
4
-treated mice. Yet, ST2 deficiency muted these IL-33 activities. Regulatory T cells from IL-33–treated mice also showed significantly stronger activities in suppressing smooth muscle cell inflammatory cytokine and chemokine expression, macrophage MMP expression, and in increasing M2 macrophage polarization than those from vehicle-treated mice. In contrast, IL-33 failed to prevent AAA and lost its beneficial activities in CaPO
4
-treated mice after selective depletion of regulatory T cells.

Conclusions—
Together, this study established a role of IL-33 in protecting mice from AAA formation by enhancing ST2-dependent aortic and systemic regulatory T-cell expansion and their immunosuppressive activities.
Chronic Calmodulin-Kinase II Activation Drives Disease Progression in Mutation-Specific Hypertrophic Cardiomyopathy
Authors: Lehman Sarah J. , Tal-Grinspan Lauren , Lynn Melissa L. , Strom Joshua , Benitez Grace E. , Anderson Mark E. , Tardiff Jil C. 
Published: January 2019

Background:
Although the genetic causes of hypertrophic cardiomyopathy (HCM) are widely recognized, considerable lag in the development of targeted therapeutics has limited interventions to symptom palliation. This is in part attributable to an incomplete understanding of how point mutations trigger pathogenic remodeling. As a further complication, similar mutations within sarcomeric genes can result in differential disease severity, highlighting the need to understand the mechanism of progression at the molecular level. One pathway commonly linked to HCM progression is calcium homeostasis dysregulation, though how specific mutations disrupt calcium homeostasis remains unclear.

Methods:

To evaluate the effects of early intervention in calcium homeostasis, we used 2 mouse models of sarcomeric HCM (cardiac troponin T R92L and R92W) with differential myocellular calcium dysregulation and disease presentation. Two modes of intervention were tested: inhibition of the autoactivated calcium-dependent kinase (calmodulin kinase II [CaMKII]) via the AC3I peptide and diltiazem, an L-type calcium channel antagonist. Two-dimensional echocardiography was used to determine cardiac function and left ventricular remodeling, and atrial remodeling was monitored via atrial mass. Sarcoplasmic reticulum Ca
2+
ATPase activity was measured as an index of myocellular calcium handling and coupled to its regulation via the phosphorylation status of phospholamban.

Results:

We measured an increase in phosphorylation of CaMKII in R92W animals by 6 months of age, indicating increased autonomous activity of the kinase in these animals. Inhibition of CaMKII led to recovery of diastolic function and partially blunted atrial remodeling in R92W mice. This improved function was coupled to increased sarcoplasmic reticulum Ca
2+
ATPase activity in the R92W animals despite reduction of CaMKII activation, likely indicating improvement in myocellular calcium handling. In contrast, inhibition of CaMKII in R92L animals led to worsened myocellular calcium handling, remodeling, and function. Diltiazem-HCl arrested diastolic dysfunction progression in R92W animals only, with no improvement in cardiac remodeling in either genotype.

Conclusions:
We propose a highly specific, mutation-dependent role of activated CaMKII in HCM progression and a precise therapeutic target for clinical management of HCM in selected cohorts. Moreover, the mutation-specific response elicited with diltiazem highlights the necessity to understand mutation-dependent progression at a molecular level to precisely intervene in disease progression.
Trends in Statin Use Among US Adults With Chronic Kidney Disease, 1999–2014
Authors: Mefford Matthew T. , Rosenson Robert S. , Deng Luqin , Tanner Rikki M. , Bittner Vera , Safford Monika M. , Coll Blai , Mues Katherine E. , Monda Keri L. , Muntner Paul 
Published: January 2019

Background

The 2013 American College of Cardiology/American Heart Association cholesterol guidelines recognize cardiovascular disease and diabetes mellitus but not chronic kidney disease (
CKD
) as high‐risk conditions warranting statin therapy. Statin use may be lower for adults with
CKD
compared with adults with conditions that have guideline indications for statin use.

Methods and Results

We analyzed data from the National Health and Nutrition Examination Surveys from 1999–2002 through 2011–2014 to determine trends in the percentage of
US
adults ≥20 years of age with and without
CKD
taking statins.
CKD
was defined by an estimated glomerular filtration rate <60 mL/min per 1.73m
2
or albumin‐to‐creatinine ratio ≥30 mg/g. Statin use was identified through a medication inventory. Between 1999–2002 and 2011–2014, the percentage of adults taking statins increased from 17.6% to 35.7% among those with
CKD
and from 6.8% to 14.7% among those without
CKD
. After multivariable adjustment, adults with
CKD
were not more likely to be taking statins compared with those without
CKD
(prevalence ratio, 1.01; 95% CI] 0.96–1.08). Among adults without a history of cardiovascular disease, those with
CKD
but not diabetes mellitus were less likely to be taking statins compared with those with diabetes mellitus but not
CKD
(prevalence ratio, 0.54; 95%
CI
, 0.44–0.66). Among adults with a history of cardiovascular disease, there was no difference in statin use between those with
CKD
but not diabetes mellitus versus those with diabetes mellitus but not
CKD
(prevalence ratio, 0.95; 95%
CI
, 0.79–1.15).

Conclusions

CKD
does not appear to be a major stimulus for statin use among
US
adults.
Emergent Management of Tandem Lesions in Acute Ischemic Stroke
Authors: Jadhav Ashutosh P. , Zaidat Osama O. , Liebeskind David S. , Yavagal Dileep R. , Haussen Diogo C. , Hellinger Frank R. , Jahan Reza , Jumaa Mouhammad A. , Szeder Viktor , Nogueira Raul G. , Jovin Tudor G. 
Published: January 2019

Background and Purpose—
Although intracranial thrombectomy represents the standard treatment approach for anterior circulation tandem occlusions, whether the extracranial lesion requires acute stenting remains unclear. Our aim was to investigate differences in clinical and procedural outcomes related to stenting extracranial lesions in a registry of patients undergoing thrombectomy for acute stroke.

Methods—
Data were analyzed from the STRATIS registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke)—a prospective, nonrandomized study of patients undergoing neurothrombectomy with the Solitaire device. A total of 984 patients treated at 55 sites were analyzed. Univariate and multivariable logistic regression was used to assess relationship between outcome and procedural technique.

Results—

Of 147 (14.9%) patients with tandem lesions treated, stenting of the extracranial lesion during thrombectomy was performed in 80 patients and withheld in 67 patients. There were no differences between groups with respect to age, ASPECTS (Alberta Stroke Program Early CT Score), or intravenous-tPA (tissue-type plasminogen activator) use. However, the patients in the stenting group had lower baseline National Institutes of Health Stroke Scale (16 versus 17.9;
P
=0.07), shorter onset to arterial puncture time (133.6 versus 163.4 minutes;
P
=0.04), and lower rates of atrial fibrillation (6.3% versus 25.4%) as compared to the nonstenting group. Good outcomes (modified Rankin Scale, 0–2 at 90 days) were higher in the stenting group (68.5% versus 42.2%;
P
=0.003) with no difference in mortality or symptomatic hemorrhage. After adjustment for covariates, stenting continued to be associated with superior outcomes.

Conclusions—
Acute stenting of an extracranial carotid stenosis during neurothrombectomy can be achieved with equal safety compared with no stenting. Carotid stenting in the acute phase may lead to better outcomes; this should ideally be confirmed by randomized trials.
Are the Near-Antarctic Easterly Winds Weakening in Response to Enhancement of the Southern Annular Mode?
Authors: Hazel Julia E. , Stewart Andrew L. 
Published: January 2019

AbstractPrevious studies have highlighted the sensitivity of the Southern Ocean circulation to the strengthening, poleward-shifting westerlies, associated with the increasingly positive southern annular mode (SAM). The impacts of the SAM have been hypothesized to weaken momentum input to the ocean from the easterly winds around the Antarctic margins. Using ERA-Interim data, the authors show that the circumpolar-averaged easterly wind stress has not weakened over the past 3–4 decades, and, if anything, has slightly strengthened by around 7%. However, there has been a substantial increase in the seasonality of the easterlies, with a weakening of the easterly winds during austral summer and a strengthening during winter. A similar trend in the seasonality of the easterlies is found in three other reanalysis products that compare favorably with Antarctic meteorological observations. The authors associate the strengthening of the easterly winds during winter with an increase in the pressure gradient between the coast and the pole. Although the trend in the overall easterly wind strength is small, the change in the seasonal cycle may be expected to reduce the shoreward Ekman transport of summer surface waters and also to admit more warm Circumpolar Deep Water to the continental shelf in summer. Changes in the seasonal cycle of the near-coastal winds may also project onto seasonal formation and export of sea ice, fluctuations in the strengths of the Weddell and Ross Gyres, and seasonal export of Antarctic Bottom Water from the continental shelf.
Surface modification of polylactic acid (PLA) and polyglycolic acid (PGA) monofilaments via the cold plasma method for acupoint catgut-embedding therapy applications
Authors: Fu Shaoju , Zhang Peihua 
Published: January 2019

Polylactic acid (PLA) and polyglycolic acid (PGA) monofilaments have been the most recently, widely used acupoint catgut-embedding therapy (ACET) biodegradable materials. However, their poor hydrophilicity and cell adhesion are common limitations during applications. To improve their surface properties, modification technologies should be generally applied. This paper firstly adapted polymer chips to produce four types of PLA and PGA monofilaments, and then attempted cold oxygen plasma treatment for surface modification. Afterwards, the modified monofilaments were fully characterized with respect to structure, mechanical and in vitro properties. The results showed that both the PLA and PGA monofilaments became coarser after modification, and their hydrophilicity was improved, while their weight and diameter sizes were slightly decreased. The tensile properties and flexibility of the modified samples changed little, and their swelling ratio increased sharply. All the prepared samples exhibited good cell viability, with more than 75% of cells being viable. Sample PM-PLA2 (plasma-modified PLA2) and sample PM-PGA2 (plasma-modified PGA2) presented the largest cell attachment ratio (cultured for 48 h) at 52.16% ± 1.05% and 58.39% ± 2.07%, respectively. In sum, this cold plasma method successfully improved the hydrophilicity and in vitro properties of PLA and PGA monofilaments, while retaining the other excellent properties, and warrants further study to develop new PLA and PGA-embedding materials with outstanding clinical efficacy.
Aging Expectations and Attitudes: Associations With Types of Older Adult Contact
Authors: Hawkley Louise C. , Norman Gregory J. , Agha Zia 
Published: January 2019

Objectives: To evaluate the role of contact with older adults in explaining expectations about aging and attitudes toward own aging. Method: A representative sample of 3,026 U.S. adults aged 30–89 years completed a survey online or by telephone. The survey assessed types of contact with older adults, anticipated need for help during aging, and attitudes toward their own aging. Results: Relative to older adults’ (65+ years) need for help with finances, activities of daily living, social support, and health care during aging, 30- to 64-year-old adults overestimated their expected need for help. Contact with dependent older adults was associated with greater overestimation. Diverse types of contact with older adults were associated with increased positivity toward one’s own aging. Discussion: Aging expectations may be ameliorated by exposure to diverse exemplars of aging. Future research should quantify effects of exposure types on both negative and positive attitudes toward own aging.
‘Having a mentor helped me with difficult times’: a trainee-run mentoring project
Authors: Szabo Susana , Lloyd Bonita , McKellar Duncan , Myles Hannah , Newton Heidi , Schutz Jedda , Hahn Lisa , Galletly Cherrie 
Published: January 2019

Objective: A mentoring programme was established in South Australia in 2014 by psychiatry trainees, with the goal of reducing stress and burnout amongst first-year trainees. All first-year trainees are offered the opportunity to have a senior trainee as a mentor. This article describes the mentoring programme, presents feedback from participants and identifies areas for further development. Method: The majority (72/76) of first-year trainees entering psychiatry training in South Australia from 2014–2018 were allocated a mentor. Surveys were sent out in 2014, 2015 and 2017. Twenty of 42 (48%) mentors and 17 of 42 (40%) of mentees completed a 10-item questionnaire, with free text responses. Results: Mentee feedback was mostly positive, reporting that mentors offered them reassurance and support. The most common challenges were advice about training, managing work-life balance and issues with supervision. The main barrier to the mentoring programme was lack of time to meet. Mentors identified that they would have liked more training in mentoring. Conclusion: The trainee mentoring programme has been a useful initiative. As consultant psychiatrists are likely to provide mentoring for more junior colleagues, the authors propose that training in mentoring should be part of the Royal Australian and New Zealand College of Psychiatrists education programme.