bluuebunny/crossref_metadata_2025 huggingface dataset:
Endoscopic Removal of a Duodenal-Perforating Leg of Glasses with Dormia Basket
Authors: Wang Li , Wen Wei , Huang Jiamiao , Hu Weijie , Zhou Renrong , Li Xin , Wang Xiaojiang
Published: November 2016

Ingestion of foreign bodies is common in clinical practice. Most ingested foreign bodies will pass through the gastrointestinal (GI) tract without any problems. While GI tract injury due to the ingested foreign body such as a toothpick, a fishbone, a date pit, or a chicken bone, is common, duodenal perforation is rare. In this report, our experience with this rare entity is shared. We present a 38-year-old male patient with GI tract perforation in the bulbus of the duodenum due to a leg of glasses. The patient was admitted to our hospital with severe abdominal pain. Right upper quadrant tenderness was detected at physical examination, and leukocytosis on the laboratory test results. Plain X-ray and computerized tomography showed an ingested foreign body in the bulbus of the duodenum. A leg of glasses perforating the duodenum was removed with endoscopy. The patient was managed nonoperatively, and discharged without any complications on the eighth day after endoscopy. Endoscopic removal and nonoperative management may be feasible in carefully selected patients with duodenal-perforating foreign bodies.
Sjögren Syndrome-Related Membranous Glomerulonephritis Progressing to Membranoproliferative Glomerulonephritis
Authors: Yabuuchi Junko , Suwabe Tatsuya , Ueno Toshiharu , Hoshino Junichi , Sekine Akinari , Hayami Noriko , Oguro Masahiko , Kunisawa Kyohei , Kawada Masahiro , Yamanouchi Masayuki , Sumida Keiichi , Mizuno Hiroki , Hasegawa Eiko , Sawa Naoki , Takaichi Kenmei , Ohashi Kenichi , Fujii Takeshi , Ubara Yoshifumi
Published: November 2016

We report a case of glomerulopathy in a 36-year-old Japanese woman with primary Sjögren syndrome (pSS). The first renal biopsy suggested membranous glomerulonephritis. However, repeat biopsy was performed after 16 years because of increased proteinuria, revealing membranoproliferative glomerulonephritis with mesangial deposits, subendothelial deposits, and subepithelial deposits. Immunofluorescent studies showed predominant deposition of IgG2 and IgG4. This patient was positive for antinuclear antibody and anti-SS-A antibody. Sicca syndrome was confirmed by a positive Schirmer test and positive Rose Bengal test. Therefore, pSS-related glomerulopathy was considered to be the most likely diagnosis.
Scleroderma with Nodular Scleroderma
Authors: Srisuttiyakorn Chutika , Aunhachoke Kobkul
Published: November 2016

Background: Nodular scleroderma is a rare variant of scleroderma which can occur in connection with systemic sclerosis or morphea. A biopsy from the lesion can demonstrate the scleroderma pattern, i.e., keloid pattern or mixed type. Treatment is challenging, and several treatments modalities have been reported with unsatisfactory results. Main Observations: We present a case of systemic sclerosis in a 50-year-old female who developed nodular scleroderma in the absence of deterioration of the scleroderma condition. Although no additional treatment was given, the lesions remained stable without progression. Conclusions: Although this condition is rare, it has been reported sporadically, and clinicians should be able to recognize this variant in cases of scleroderma presenting with firm nodules or plaques.
Rare Paravertebral and Skull Base Metastases in Prostate Cancer
Authors: Samuel Gbeminiyi , Isbell Amir , Ogbonna Onyekachi , Iftikhar Hasan , Sakruti Susmita , Atanda Adebayo , Manchandani Raj P.
Published: November 2016

Prostate cancer is the most commonly diagnosed visceral cancer in the United States. A majority of cases exhibit an insidious course and nonaggressive tumor behavior. Prostate cancer can manifest as lesions which remain localized, regionally invading or metastasize to lymph nodes, bones, and lungs. Here, we report a unique case of metastatic prostate cancer to the right upper mediastinum, presenting as a paravertebral mass within 2 years of initial tissue diagnosis. Paravertebral spread has not been described for prostate cancer, and herein, we discuss the clinical presentation, diagnostic workup, and possible therapeutic options available in light of the literature.
Williams Syndrome and 15q Duplication: Coincidence versus Association
Authors: Khokhar Aditi , Agarwal Swashti , Perez-Colon Sheila
Published: November 2016

Williams syndrome is a multisystem disorder caused by contiguous gene deletion in 7q11.23, commonly associated with distinctive facial features, supravalvular aortic stenosis, short stature, idiopathic hypercalcemia, developmental delay, joint laxity, and a friendly personality. The clinical features of 15q11q13 duplication syndrome include autism, mental retardation, ataxia, seizures, developmental delay, and behavioral problems. We report a rare case of a girl with genetically confirmed Williams syndrome and coexisting 15q duplication syndrome. The patient underwent treatment for central precocious puberty and later presented with primary amenorrhea. The karyotype revealed 47,XX,+mar. FISH analysis for the marker chromosome showed partial trisomy/tetrasomy for proximal chromosome 15q (15p13q13). FISH using an ELN-specific probe demonstrated a deletion in the Williams syndrome critical region in 7q11.23. To our knowledge, a coexistence of Williams syndrome and 15q duplication syndrome has not been reported in the literature. Our patient had early pubertal development, which has been described in some patients with Williams syndrome. However, years later after discontinuing gonadotropin-releasing hormone analogue treatment, she developed primary amenorrhea.
Combined Acute Haemolytic and Secondary Angle Closure Glaucoma following Spontaneous Intraocular Haemorrhages in a Patient on Warfarin
Authors: Andreatta Walter , Boukouvala Stavroula , Bansal Atul
Published: November 2016

Background: To report the first described case of combined haemolytic and acute angle closure glaucoma secondary to spontaneous intraocular haemorrhages in a patient on excessive anticoagulation. To the best of our knowledge, this is the first case reported in the literature presenting with raised intraocular pressure due to both mechanisms. Case Description: A 90-year-old woman presented with acute pain and reduction in vision in the left eye. Her intraocular pressure (IOP) was 55 mm Hg. There were red tinted blood cells in the anterior chamber giving it a reddish hue. The patient was known to have advanced wet macular degeneration. She was taking oral warfarin for atrial fibrillation. Her international normalised ratio (INR) was 7.7. B-scan ultrasound of posterior segment showed vitreous and suprachoroidal haemorrhages. An ultrabiomicroscopic examination confirmed open angles. A diagnosis of haemolytic glaucoma secondary to intraocular haemorrhages was made. The IOP was controlled medically. Warfarin was withdrawn and oral vitamin K therapy was initiated leading to a rapid INR reduction. Three days later, her anterior chamber became progressively shallower causing a secondary acute angle closure which was managed medically. After 2 months, the left IOP was well-controlled without any medications and the eye was not inflamed. Her vision in that eye remained perception of light. Conclusion: Patients with suprachoroidal haemorrhages should be closely monitored as they might subsequently develop acute angle closure despite an initially open angle and well-controlled INR and IOP. Excessive anticoagulation needs to be prevented to minimise the risk of sight-threatening complications.
Reduced Expression of Cytoskeletal and Extracellular Matrix Genes in Human Adult Retinal Pigment Epithelium Cells Exposed to Simulated Microgravity
Authors: Corydon Thomas J. , Mann Vivek , Slumstrup Lasse , Kopp Sascha , Sahana Jayashree , Askou Anne Louise , Magnusson Nils E. , Echegoyen David , Bek Toke , Sundaresan Alamelu , Riwaldt Stefan , Bauer Johann , Infanger Manfred , Grimm Daniela
Published: November 2016

Background/Aims: Microgravity (µg) has adverse effects on the eye of humans in space. The risk of visual impairment is therefore one of the leading health concerns for NASA. The impact of µg on human adult retinal epithelium (ARPE-19) cells is unknown. Methods: In this study we investigated the influence of simulated µg (s-µg; 5 and 10 days (d)), using a Random Positioning Machine (RPM), on ARPE-19 cells. We performed phase-contrast/fluorescent microscopy, qRT-PCR, Western blotting and pathway analysis. Results: Following RPM-exposure a subset of ARPE-19 cells formed multicellular spheroids (MCS), whereas the majority of the cells remained adherent (AD). After 5d, alterations of F-actin and fibronectin were observed which reverted after 10d-exposure, suggesting a time-dependent adaptation to s-µg. Gene expression analysis of 12 genes involved in cell structure, shape, adhesion, migration, and angiogenesis suggested significant changes after a 10d-RPM-exposure. 11 genes were down-regulated in AD and MCS 10d-RPM-samples compared to 1g, whereas FLK1 was up-regulated in 5d- and 10d-RPM-MCS-samples. Similarly, TIMP1 was up-regulated in 5d-RPM-samples, whereas the remaining genes were down-regulated in 5d-RPM-samples. Western blotting revealed similar changes in VEGF, β-actin, laminin and fibronectin of 5d-RPM-samples compared to 10d, whereas different alterations of β-tubulin and vimentin were observed. The pathway analysis showed complementing effects of VEGF and integrin β-1. Conclusions: These findings clearly show that s-µg induces significant alterations in the F-actin-cytoskeleton and cytoskeleton-related proteins of ARPE-19, in addition to changes in cell growth behavior and gene expression patterns involved in cell structure, growth, shape, migration, adhesion and angiogenesis.
Lifetime Risk and Risk Factors for Abdominal Aortic Aneurysm in a 24-Year Prospective Study
Authors: Tang Weihong , Yao Lu , Roetker Nicholas S. , Alonso Alvaro , Lutsey Pamela L. , Steenson Carol C. , Lederle Frank A. , Hunter David W. , Bengtson Lindsay G.S. , Guan Weihua , Missov Emil , Folsom Aaron R.
Published: November 2016

Objective—

Abdominal aortic aneurysm (AAA) is an important vascular disease in older adults, but data on lifetime risk of AAA are sparse. We examined lifetime risk of AAA in a community-based cohort and prospectively assessed the association between midlife cardiovascular risk factors and AAAs.

Approach and Results—

In ARIC study (Atherosclerosis Risk in Communities), 15 792 participants were recruited at visit 1 in 1987 to 1989 and followed up through 2013. Longitudinal smoking status was defined using smoking behavior ascertained from visit 1 (1987–1989) to visit 4 (1996–1998). We followed up participants for incident, clinical AAAs using hospital discharge diagnoses, Medicare outpatient diagnoses, or death certificates through 2011 and identified 590 incident AAAs. An abdominal ultrasound was conducted in 2011 to 2013 in 5911 surviving participants, and 75 asymptomatic AAAs were identified. We estimated the lifetime risk of AAA from the index age 45 years through 85 years of age. At age 45, the lifetime risk for AAA was 5.6% (95% confidence interval, 4.8–6.1) and was higher in men (8.2%) and current smokers (10.5%). Smokers who quit smoking between visit 1 and visit 4 had a 29% lower AAA lifetime risk compared with continuous smokers but had a higher risk than pre-visit 1 quitters. The lifetime risk of rupture or medical intervention was 1.6% (95% confidence interval, 1.2–1.8). Smoking, white race, male sex, greater height, and greater low-density lipoprotein or total cholesterol were associated with an increased risk of clinical AAA and asymptomatic AAA.

Conclusions—

At least 1 in 9 middle-aged current smokers developed AAA in their lifetime. Smoking cessation reduced the lifetime risk of AAA.
Rac2 Modulates Atherosclerotic Calcification by Regulating Macrophage Interleukin-1β Production
Authors: Ceneri Nicolle , Zhao Lina , Young Bryan D. , Healy Abigail , Coskun Suleyman , Vasavada Hema , Yarovinsky Timur O. , Ike Kenneth , Pardi Ruggero , Qin Lingfen , Qin Li , Tellides George , Hirschi Karen , Meadows Judith , Soufer Robert , Chun Hyung J. , Sadeghi Mehran M. , Bender Jeffrey R. , Morrison Alan R.
Published: November 2016

Objective—

The calcium composition of atherosclerotic plaque is thought to be associated with increased risk for cardiovascular events, but whether plaque calcium itself is predictive of worsening clinical outcomes remains highly controversial. Inflammation is likely a key mediator of vascular calcification, but immune signaling mechanisms that promote this process are minimally understood.

Approach and Results—

Here, we identify Rac2 as a major inflammatory regulator of signaling that directs plaque osteogenesis. In experimental atherogenesis, Rac2 prevented progressive calcification through its suppression of Rac1-dependent macrophage interleukin-1β (IL-1β) expression, which in turn is a key driver of vascular smooth muscle cell calcium deposition by its ability to promote osteogenic transcriptional programs. Calcified coronary arteries from patients revealed decreased Rac2 expression but increased IL-1β expression, and high coronary calcium burden in patients with coronary artery disease was associated with significantly increased serum IL-1β levels. Moreover, we found that elevated IL-1β was an independent predictor of cardiovascular death in those subjects with high coronary calcium burden.

Conclusions—

Overall, these studies identify a novel Rac2-mediated regulation of macrophage IL-1β expression, which has the potential to serve as a powerful biomarker and therapeutic target for atherosclerosis.
Elevated Homocysteine Concentrations Decrease the Antihypertensive Effect of Angiotensin-Converting Enzyme Inhibitors in Hypertensive Patients
Authors: Qin Xianhui , Li Youbao , Sun Ningling , Wang Hong , Zhang Yan , Wang Jiguang , Li Jianping , Xu Xin , Liang Min , Nie Jing , Wang Binyan , Cheng Xiaoshu , Li Nanfang , Sun Yingxian , Zhao Lianyou , Wang Xiaobin , Hou Fan Fan , Huo Yong
Published: November 2016

Objective—

We aimed to examine whether baseline homocysteine (Hcy) concentrations affect antihypertensive responses to enalapril treatment among previously untreated hypertensive patients (n=10 783) in the CSPPT (China Stroke Primary Prevention Trial).

Approach and Results—

After a 3-week run-in treatment with a daily dose of 10 mg enalapril, eligible hypertensive patients were randomly assigned to a double-blind daily treatment of a tablet of either enalapril (10 mg) and folic acid (0.8 mg) or enalapril (10 mg) alone for a median of 4.5 years. After the 3-week treatment period with enalapril alone, the systolic blood pressure–lowering effect was significantly reduced by 1.39 (95% confidence interval 0.40–2.37) and 3.25 (95% confidence interval 1.98–4.52) mm Hg, respectively, in those with baseline Hcy concentrations of 10 to 15 and ≥15 μmol/L (
P
for trend <0.001) as compared with those with Hcy concentration of <10 μmol/L. Similar results were observed after a 15-week treatment period with enalapril alone. After a median 4.5-year enalapril-based antihypertensive treatment period, compared with those with Hcy concentration of <10 μmol/L, the systolic blood pressure–lowering effect was still significantly reduced by 0.77 (95% confidence interval 0.01–1.53) and 1.70 (95% confidence interval 0.72–2.68) mm Hg, respectively, in those with Hcy concentrations of 10 to 15 and ≥15 μmol/L (
P
for trend <0.001). In addition, participants with higher baseline Hcy concentrations had persistently higher systolic blood pressure levels across the entire study treatment period. Similarly, baseline Hcy concentrations were inversely associated with diastolic blood pressure reduction during the short-term enalapril alone treatment. However, the inverse association between baseline Hcy and diastolic blood pressure reduction was attenuated and became insignificant after the long-term enalapril-based treatment period.

Conclusions—

Elevated Hcy concentrations significantly decreased the antihypertensive effect of the short-term and long-term enalapril-based antihypertensive treatment in previously untreated hypertensive patients.
High Structural Stress and Presence of Intraluminal Thrombus Predict Abdominal Aortic Aneurysm
18
F-FDG Uptake
Authors: Huang Yuan , Teng Zhongzhao , Elkhawad Maysoon , Tarkin Jason M. , Joshi Nikhil , Boyle Jonathan R. , Buscombe John R. , Fryer Timothy D. , Zhang Yongxue , Park Ah Yeon , Wilkinson Ian B. , Newby David E. , Gillard Jonathan H. , Rudd James H. F.
Published: November 2016

Background—

Abdominal aortic aneurysm (AAA) wall inflammation and mechanical structural stress may influence AAA expansion and lead to rupture. We hypothesized a positive correlation between structural stress and fluorine-18-labeled 2-deoxy-2-fluoro-
d
-glucose (
18
F-FDG) positron emission tomography–defined inflammation. We also explored the influence of computed tomography–derived aneurysm morphology and composition, including intraluminal thrombus, on both variables.

Methods and Results—

Twenty-one patients (19 males) with AAAs below surgical threshold (AAA size was 4.10±0.54 cm) underwent
18
F-FDG positron emission tomography and contrast-enhanced computed tomography imaging. Structural stresses were calculated using finite element analysis. The relationship between maximum aneurysm
18
F-FDG standardized uptake value within aortic wall and wall structural stress, patient clinical characteristics, aneurysm morphology, and compositions was explored using a hierarchical linear mixed-effects model. On univariate analysis, local aneurysm diameter, thrombus burden, extent of calcification, and structural stress were all associated with
18
F-FDG uptake (
P
<0.05). AAA structural stress correlated with
18
F-FDG maximum standardized uptake value (slope estimate, 0.552;
P
<0.0001). Multivariate linear mixed-effects analysis revealed an important interaction between structural stress and intraluminal thrombus in relation to maximum standardized uptake value (fixed effect coefficient, 1.68 [SE, 0.10];
P
<0.0001). Compared with other factors, structural stress was the best predictor of inflammation (receiver-operating characteristic curve area under the curve =0.59), with higher accuracy seen in regions with high thrombus burden (area under the curve =0.80). Regions with both high thrombus burden and high structural stress had higher
18
F-FDG maximum standardized uptake value compared with regions with high thrombus burdens but low stress (median [interquartile range], 1.93 [1.60–2.14] versus 1.14 [0.90–1.53];
P
<0.0001).

Conclusions—

Increased aortic wall inflammation, demonstrated by
18
F-FDG positron emission tomography, was observed in AAA regions with thick intraluminal thrombus subjected to high mechanical stress, suggesting a potential mechanistic link underlying aneurysm inflammation.
Outcome Implication of Aortic Valve Area Normalized to Body Size in Asymptomatic Aortic Stenosis
Authors: Tribouilloy Christophe , Bohbot Yohann , Maréchaux Sylvestre , Debry Nicolas , Delpierre Quentin , Peltier Marcel , Diouf Momar , Slama Michel , Messika-Zeitoun David , Rusinaru Dan
Published: November 2016

Background—

Current guidelines define severe aortic stenosis in patients with aortic valve area normalized to body surface area (AVA/BSA) <0.6 cm
2
/m
2
; yet, this cutoff has never been validated. Moreover, it is not known whether AVA normalization to other body size indexes allows improved outcome prediction. We aim to test the value of AVA normalized to body size for outcome prediction in asymptomatic aortic stenosis.

Methods and Results—

We included 289 patients with asymptomatic aortic stenosis, preserved ejection fraction, and AVA<1.3 cm
2
at diagnosis. The outcome measure was the occurrence of aortic valve replacement or all-cause death or during follow-up. AVA was normalized to BSA, height, weight, and body mass index. For each normalized index, patients in the lowest tertile were at high risk of events whereas outcome was similar for the other tertiles. High risk of events was observed with AVA/BSA <0.4 cm
2
/m
2
(adjusted hazard ratio [HR], 3.42 [2.09–5.60]), AVA/height <0.45 cm
2
/m (adjusted HR, 3.99 [2.42–6.60]), AVA/weight <0.01 cm
2
/kg (adjusted HR, 3.37 [2.07–5.49]), and AVA/body mass index <0.029 cm
2
/kg per meter square (adjusted HR, 3.23 [1.99–5.24]). Mortality risk was high with AVA/height <0.45 cm
2
/m (adjusted HR, 2.18 [1.28–3.71]), followed by AVA/BSA <0.40 cm
2
/m
2
(adjusted HR, 1.84 [1.09–3.11]), AVA/weight <0.01 cm
2
/kg (adjusted HR, 1.78 [1.07–2.98]), and AVA/body mass index <0.029 cm
2
/kg per meter square (adjusted HR, 1.75 [1.04–2.93]). AVA/height showed better predictive performance than AVA/BSA with improved reclassification and better discrimination (net reclassification improvement: 0.33 versus 0.28; integrated discrimination improvement: 0.10 versus 0.08; C statistic: 0.67 versus 0.65), whereas AVA/weight and AVA/body mass index showed lower predictive capacity.

Conclusions—

Among AVA normalization methods, AVA/height <0.45 cm
2
/m followed by AVA/BSA <0.40 cm
2
/m
2
seem as robust parameters for defining high risk in asymptomatic aortic stenosis. The prognostic value of AVA/height deserves future research.
Greater Volume but not Higher Density of Abdominal Aortic Calcium Is Associated With Increased Cardiovascular Disease Risk
Authors: Forbang Nketi I. , Michos Erin D. , McClelland Robyn L. , Remigio-Baker Rosemay A. , Allison Matthew A. , Sandfort Veit , Ix Joachim H. , Thomas Isac , Rifkin Dena E. , Criqui Michael H.
Published: November 2016

Background—

Abdominal aortic calcium (AAC) and coronary artery calcium (CAC) independently and similarly predict cardiovascular disease (CVD) events. The standard AAC and CAC score, the Agatston method, upweights for greater calcium density, thereby modeling higher calcium density as a CVD hazard.

Methods and Results—

Computed tomography scans were used to measure AAC and CAC volume and density in a multiethnic cohort of community-dwelling individuals, and Cox proportional hazard was used to determine their independent association with incident coronary heart disease (CHD, defined as myocardial infarction, resuscitated cardiac arrest, or CHD death), cardiovascular disease (CVD, defined as CHD plus stroke and stroke death), and all-cause mortality. In 997 participants with Agatston AAC and CAC scores >0, the mean age was 66±9 years, and 58% were men. During an average follow-up of 9 years, there were 77 CHD, 118 CVD, and 169 all-cause mortality events. In mutually adjusted models, additionally adjusted for CVD risk factors, an increase in ln(AAC volume) per standard deviation was significantly associated with increased all-cause mortality (hazard ratio=1.20; 95% confidence interval, 1.08–1.33;
P
<0.01) and an increased ln(CAC volume) per standard deviation was significantly associated with CHD (hazard ratio=1.17; 95% confidence interval, 1.04–1.59;
P
=0.02) and CVD (hazard ratio=1.20; 95% confidence interval, 1.05–1.36;
P
<0.01). In contrast, both AAC and CAC density were not significantly associated with CVD events.

Conclusions—

The Agatston method of upweighting calcium scores for greater density may be inappropriate for CVD risk prediction in both the abdominal aorta and coronary arteries.
Discordance Between Resting and Hyperemic Indices of Coronary Stenosis Severity
Authors: Hennigan Barry , Oldroyd Keith G. , Berry Colin , Johnson Nils , McClure John , McCartney Peter , McEntegart Margaret B. , Eteiba Hany , Petrie Mark C. , Rocchiccioli Paul , Good Richard , Lindsay Martin M. , Hood Stuart , Watkins Stuart
Published: November 2016

Background—

Distal coronary to aortic pressure ratio (Pd/Pa) and instantaneous wave-free ratio (iFR) are indices of functional significance of a coronary stenosis measured without hyperemia. It has been suggested that iFR has superior diagnostic accuracy to Pd/Pa when compared with fractional flow reserve (FFR).

We hypothesized that in comparison with FFR, revascularization decisions based on either binary cutoff values for iFR and Pd/Pa or hybrid strategies incorporating iFR or Pd/Pa will result in similar levels of disagreement.

Methods and Results—

This is a prospective study in consecutive patients undergoing FFR for clinical indications using proprietary software to calculate iFR. We measured Pd/Pa, iFR, FFR, and hyperemic iFR. Diagnostic accuracy versus FFR ≤0.80 was calculated using binary cutoff values of ≤0.90 for iFR and ≤0.92 for Pd/Pa, and adenosine zones for iFR of 0.86 to 0.93 and Pd/Pa of 0.87 to 0.94 in the hybrid strategy. One hundred ninety-seven patients with 257 stenoses (mean diameter stenosis 48%) were studied. Using binary cutoffs, diagnostic accuracy was similar for iFR and resting Pd/Pa with misclassification rates of 21% versus 20.2% (
P
=0.85). In the hybrid analysis, 54% of iFR cases and 53% of Pd/Pa cases were outside the adenosine zone and rates of misclassification were 9.4% versus 11.9% (
P
=0.55).

Conclusions—

Binary cutoff values for iFR and Pd/Pa result in misclassification of 1 in 5 lesions. Using a hybrid strategy, approximately half of the patients do not receive adenosine, but 1 in 10 lesions are still misclassified. The use of nonhyperemic indices of stenosis severity cannot be recommended for decision making in the catheterization laboratory.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT02377310.
MiR‐590 Promotes Transdifferentiation of Porcine and Human Fibroblasts Toward a Cardiomyocyte‐Like Fate by Directly Repressing Specificity Protein 1
Authors: Singh Vivek P. , Mathison Megumi , Patel Vivekkumar , Sanagasetti Deepthi , Gibson Brian W. , Yang Jianchang , Rosengart Todd K.
Published: November 2016

Background

Reprogramming of cardiac fibroblasts into induced cardiomyocyte‐like cells represents a promising potential new therapy for treating heart disease, inducing significant improvements in postinfarct ventricular function in rodent models. Because reprogramming factors effective in transdifferentiating rodent cells are not sufficient to reprogram human cells, we sought to identify reprogramming factors potentially applicable to human studies.

Methods and Results

Lentivirus vectors expressing Gata4, Mef2c, and Tbx5 (
GMT
); Hand2 (H), Myocardin (My), or microRNA (miR)‐590 were administered to rat, porcine, and human cardiac fibroblasts in vitro. induced cardiomyocyte‐like cell production was then evaluated by assessing expression of the cardiomyocyte marker, cardiac troponin T (
cTnT
), whereas signaling pathway studies were performed to identify reprogramming factor targets.
GMT
administration induced
cTnT
expression in ≈6% of rat fibroblasts, but failed to induce
cTnT
expression in porcine or human cardiac fibroblasts. Addition of H/My and/or miR‐590 to
GMT
administration resulted in
cTNT
expression in ≈5% of porcine and human fibroblasts and also upregulated the expression of the cardiac genes,
MYH
6 and
TNNT
2. When cocultured with murine cardiomyocytes,
cTnT
‐expressing porcine cardiac fibroblasts exhibited spontaneous contractions. Administration of
GMT
plus either H/My or miR‐590 alone also downregulated fibroblast genes
COL
1A1 and
COL
3A1. miR‐590 was shown to directly suppress the zinc finger protein, specificity protein 1 (Sp1), which was able to substitute for miR‐590 in inducing cellular reprogramming.

Conclusions

These data support porcine studies as a surrogate for testing human cardiac reprogramming, and suggest that miR‐590‐mediated repression of Sp1 represents an alternative pathway for enhancing human cardiac cellular reprogramming.
Effect of High (200 μg/kg per Minute) Adenosine Dose Infusion on Fractional Flow Reserve Variability
Authors: Alexopoulos Dimitrios , Xanthopoulou Ioanna , Tsigkas Grigorios , Koutsogiannis Nikolaos , Salata Paraskevi , Armylagos Stylianos , Moulias Athanasios , Davlouros Periklis
Published: November 2016

Background

Variations in distal coronary pressure (Pd)/aortic pressure (Pa) ratio during steady‐state hyperemia with standard (140 μg/kg per minute) adenosine dose may hamper accurate fractional flow reserve assessment. This study investigated to what extent an increased adenosine dose can overcome Pd/Pa variation.

Methods and Results

In a prospective, single‐arm study, out of 95 prospectively screened patients, 38 (40.0%) exhibited significant (≥0.05 difference of max Pd/Pa minus min Pd/Pa) variations in Pd/Pa from 15 s post Pd/Pa dip and until the end of a 3‐minute adenosine (140 μg/kg per minute) infusion. Thirty patients agreed to participate in a post 5‐minute repeat fractional flow reserve assessment using 200 μg/kg per minute 3‐minute adenosine infusion. The study's co‐primary end point of Pd/Pa coefficient of dispersion was lower for the high versus standard adenosine dose: 1.31 (1.13–2.72) versus 2.76 (2.38–5.60),
P
=0.002. The study's co‐primary end point of ΔPd/Pa was also lower for the high versus standard adenosine dose: 0.065 (0.038–0.10) versus 0.08 (0.06–0.11),
P
=0.002. This difference was mainly driven by the lowering effect of the high adenosine dose on the maximum Pd/Pa compared to the standard dose: 0.84 (0.81–0.93) versus 0.90 (0.83–0.95),
P
=0.007, while minimum Pd/Pa remained unaffected. High adenosine dose was adequately tolerated by all patients, without requiring infusion discontinuation in any case.

Conclusions

Pd/Pa variability is frequently observed during standard adenosine infusion and is significantly decreased following a high (200 μg/kg per minute) adenosine dose. This is achieved without a significant difference in the minimum Pd/Pa.

Clinical Trial Registration

URL
:
https://www.clinicaltrials.gov
. Unique identifier:
NCT
02350439.
Histological Findings and Predictors of Cerebral Debris From Transcatheter Aortic Valve Replacement: The ALSTER Experience
Authors: Schmidt Tobias , Akdag Ozan , Wohlmuth Peter , Thielsen Thomas , Schewel Dimitry , Schewel Jury , Alessandrini Hannes , Kreidel Felix , Bader Ralf , Romero Maria , Ladich Elena , Virmani Renu , Schäfer Ulrich , Kuck Karl‐Heinz , Frerker Christian
Published: November 2016

Background

Histopathological analyses of debris captured by a cerebral protection system during transcatheter aortic valve replacement have been reported, but the origin of the captured debris was not determined and risk factors were not defined.

Methods and Results

Embolic debris was analyzed from 322 filters used in a dual‐cerebral‐filter protection system implemented during transcatheter aortic valve replacement for 161 patients (mean age 81 years, 82 male [51%], logistic EuroSCORE 19% [interquartile range 12–31%]). The debris capture rate was high, with debris from 97% of all patients (156 of 161). No differences by filter location were found (brachiocephalic trunk 86% [139 of 161], left carotid artery 91% [147 of 161]; adjusted
P
=0.999). Five prevalent types of debris were identified: thrombus (91%), arterial wall tissue (68%), valve tissue (53%), calcification (46%), and foreign material (30%). Female sex (
P
=0.0287, odds ratio 1.364, 95% CI 1.032–1.812) and diabetes mellitus (
P
=0.0116, odds ratio 1.474, 95% CI 1.089–2.001) were significant risk factors for embolic debris. Additional analysis showed significantly more valve tissue in patients with predilation (
P
=0.0294). Stroke and transient ischemic attack rates were 0.6% each (1 of 161).

Conclusion

This study showed a high rate of embolic debris consisting of typical anatomic structures known to be altered in patients with aortic stenosis undergoing transcatheter aortic valve replacement. Female patients with diabetes mellitus have increased risk of embolic debris and should be protected by a cerebral protection system during transcatheter aortic valve replacement. Because valve tissue embolizes more often in patients with predilation, procedural planning should consider this finding. Both cerebral arteries (brachiocephalic trunk, left carotid artery) should be protected in the same way.
Baseline Predictors of Poor Outcome in Patients Too Good to Treat With Intravenous Thrombolysis
Authors: Ali Syed F. , Siddiqui Khawja , Ay Hakan , Silverman Scott , Singhal Aneesh , Viswanathan Anand , Rost Natalia , Lev Michael , Schwamm Lee H.
Published: November 2016

Background and Purpose—

Several studies have reported poor outcomes in patients too good to treat with intravenous thrombolysis because of mild or rapidly improving symptoms. We sought to determine baseline clinical and imaging predictors of poor outcome in these patients.

Methods—

Among 3950 consecutive stroke admissions (2009–2015) in our local Get With the Guidelines–Stroke database, 632 patients presented ≤4.5 hours and did not receive tissue-type plasminogen activator, with 380 of 632 (60.1%) being too good to treat. Univariate and multivariable analyses explored the clinical and imaging features associated with poor outcome (defined as not being discharged to home) in these 380 cases.

Results—

Among these 380 cases, only 68% were discharged home; the other 25% to inpatient rehabilitation, 4% to a skilled nursing facility, and 3% expired or were discharged to hospice. Patients with poor outcome were older, were more often Hispanic, had more vascular risk factors, and had higher median National Institutes of Health Stroke Scale. Imaging characteristics associated with poor outcomes included large or multifocal infarction and poor collaterals. In multivariable analysis, only age, initial National Institutes of Health Stroke Scale, and infarct location were independently associated with poor outcome.

Conclusions—

Approximately one third of patients deemed too good for intravenous tissue-type plasminogen activator are unable to be discharged directly to home. Given the current safety profile of intravenous tissue-type plasminogen activator, our results suggest that the concept of being too good to treat should be re-examined with an emphasis on the features associated with poor outcome identified in our study. If replicated, these findings could be incorporated into tissue-type plasminogen activator decision-making algorithms.
Simulator for Minimally Invasive Vascular Interventions: Hardware and Software
Authors: Baier Pablo A. , Baier-Saip Jürgen A. , Schilling Klaus , Oliveira Jauvane C.
Published: November 2016

In the present work, a simulation system is proposed that can be used as an educational tool by physicians in training basic skills of minimally invasive vascular interventions. In order to accomplish this objective, initially the physical model of the wire proposed by Konings has been improved. As a result, a simpler and more stable method was obtained to calculate the equilibrium configuration of the wire. In addition, a geometrical method is developed to perform relaxations. It is particularly useful when the wire is hindered in the physical method because of the boundary conditions. Then a recipe is given to merge the physical and the geometrical methods, resulting in efficient relaxations. Moreover, tests have shown that the shape of the virtual wire agrees with the experiment. The proposed algorithm allows real-time executions, and furthermore, the hardware to assemble the simulator has a low cost.
Evaluating Control Schemes for the Third Arm of an Avatar
Authors: Laha Bireswar , Bailenson Jeremy N. , Won Andrea Stevenson , Bailey Jakki O.
Published: November 2016

Recent research on immersive virtual environments has shown that users can not only inhabit and identify with novel avatars with novel body extensions, but also learn to control novel appendages in ways beneficial to the task at hand. But how different control schemas might affect task performance and body ownership with novel avatar appendages has yet to be explored. In this article, we discuss the design of control schemas based on the theory and practice of 3D interactions applied to novel avatar bodies. Using a within-subjects design, we compare the effects of controlling a third arm with three different control schemas (bimanual, unimanual, and head-control) on task performance, simulator sickness, presence, and user preference. Both the unimanual and the head-control were significantly faster, elicited significantly higher body ownership, and were preferred over the bimanual control schema. Participants felt that the bimanual control was significantly more difficult than the unimanual control, and elicited less appendage agency than the head-control. There were no differences in reported simulator sickness. We discuss the implications of these results for interface design.
Effect of temperature on biological parameters of Aphidius matricariae, the Aphis fabae parasitoid
Authors: Pourtaghi Eliza , Shirvani Asghar , Rashki Maryam
Published: November 2016

Aphids can have devastating effects on agriculture and horticulture, and biological control agents form an important means of controlling them.Aphidius matricariaeHaliday is an important endoparasitoid for the suppression of aphid pest population outbreaks. In this research, the influence of three different temperatures, 20, 25 and 30°C, on some life cycle charactersitic ofA. matricariaewas studied under laboratory conditions when present on its host,Aphis fabaeScopoli. At 30°C, the intrinsic rate of increase, net reproductive rate, finite rate of increase, mean generation time and increase rate in one week were all significantly lower compared to the lower temperatures. The results showed that temperature had a significant effect on the duration of parasitoid development from oviposition to adult emergence. Moreover, the value of doubling time was higher at 30°C than at 20 and 25°C. The parasitoid had the shortest longevity, life span and lowest fecundity at 30°C. This investigation of temperature-dependent development and reproduction can help in the management of biological control programs. The results of this study demonstrate thatA. matricariaeis able to perform, and be mass produced, as a favorable and proper natural enemy for the biocontrol ofA. fabaeat a temperature range of 20-25°C.
Mapping Flash Flood Severity in the United States
Authors: Saharia Manabendra , Kirstetter Pierre-Emmanuel , Vergara Humberto , Gourley Jonathan J. , Hong Yang , Giroud Marine
Published: November 2016

Flash floods, a subset of floods, are a particularly damaging natural hazard worldwide because of their multidisciplinary nature, difficulty in forecasting, and fast onset that limits emergency responses. In this study, a new variable called “flashiness” is introduced as a measure of flood severity. This work utilizes a representative and long archive of flooding events spanning 78 years to map flash flood severity, as quantified by the flashiness variable. Flood severity is then modeled as a function of a large number of geomorphological and climatological variables, which is then used to extend and regionalize the flashiness variable from gauged basins to a high-resolution grid covering the conterminous United States. Six flash flood “hotspots” are identified and additional analysis is presented on the seasonality of flash flooding. The findings from this study are then compared to other related datasets in the United States, including National Weather Service storm reports and a historical flood fatalities database.
Sinisgalli e Scotellaro: Storia di un incontro
Authors: Russo Biagio
Published: November 2016

L’oggetto dell’analisi di questo saggio verte su tre direttrici. Il primo riguarda la ricostruzione storica dell’incontro, l’unico, tra Leonardo Sinisgalli e Rocco Scotellaro a Montemurro, in provincia di Potenza, attraverso fotografie e documenti. La seconda parte cerca di comprendere la natura delle relazioni tra il giovane Scotellaro, ammiratore di Sinisgalli e delle sue poesie, e il poeta-ingegnere, la cui fama era già consolidata. Nell’ultima sezione si suggerisce un’ipotesi originale: la prematura morte di Scotellaro, insieme ad altri eventi umani e professionali, ha influenzato Leonardo Sinisgalli, che dal castello di quella formidabile portaerei che era la rivista tecnico-culturale Civiltà delle macchine (1953–1958), punterà verso una rotta di impegno meridionalistico.
“Un altro tempo, che è quello della fantasia”
Authors: Grignani Maria Antonietta , Milone Federico
Published: November 2016

I quaderni autografi che attestano la redazione manoscritta de L’Orologio, conservati al Centro per gli Studi sulla tradizione manoscritta di autori moderni e contemporanei dell’Università di Pavia, sono la risorsa principale per questa indagine sulla scrittura di Carlo Levi. Attraverso lo studio delle carte è possibile infatti la ricostruzione dei tempi di composizione, grazie alle date apposte dall’autore sui quaderni; inoltre, similmente a quanto già noto per Cristo si è fermato a Eboli, si verificherà il metodo di scrittura leviano, incentrato su una stesura con pochi rifacimenti, ma spesso anticipata da scalette progettuali e strettamente intrecciata alla composizione in versi, come certificano alcune poesie che trovano spazio, a fianco alla narrazione, nelle pagine degli autografi. I vettori correttori evinti dalle varianti diranno poi del modo in cui Levi modella la lingua e la struttura del suo libro, attraverso soluzioni che vanno in direzione di un registro sostenuto e dell’incremento descrittivo.
Misteriose vicende di un tempo diverso: L’Orologio tra viaggio, sogno e magia
Authors: Acetoso Mattia
Published: November 2016

L’Orologio (1950) di Carlo Levi è stato spesso descritto come un romanzo d’impegno politico. Tuttavia, nell’immortalare un periodo di profonda trasformazione individuale e collettiva, Levi rifugge una rappresentazione mimetica del dato storico, realizzando un potente affresco espressionista. Lo svolgimento narrativo del romanzo è fortemente imperniato su una presenza diffusa di elementi onirici e magici: per penetrare la complessità di quest’opera è necessario quindi esplorare tale aspetto fondamentale della scrittura leviana. Il presente articolo analizza L’Orologio nei termini di un racconto di viaggio all’interno della coscienza fratturata di un paese, laddove viaggio, sogno e magia si rivelano misure complementari di un percorso conoscitivo di ricostruzione morale privato e collettivo insieme.
Levi, Scotellaro e il cinema documentario lucano. Saggio di antropologia storica
Authors: Esposito Vincenzo
Published: November 2016

Carlo Levi, Rocco Scotellaro, Ernesto De Martino possono essere collocati tra gli interpreti più acuti della cultura tradizionale contadina meridionale italiana dell’ultimo dopoguerra. Il loro lavoro e il loro pensiero appartengono a quel patrimonio intellettuale nato con l’impegno politico-culturale attraverso cui, alla fine della II Guerra Mondiale, furono ripensati la questione meridionale e il meridionalismo progressista. Le loro ricerche e le loro opere influenzarono altri ricercatori, altri autori. Molti cineasti si ispirarono alle loro descrizioni e alle loro interpretazioni del Mezzogiorno, realizzando decine di film di impegno meridionalistico. Scopo del mio scritto è quello di rintracciare, in prospettiva antropologico-culturale, la loro influenza su alcuni film documentari prodotti in Italia tra il 1953 e il 1976, riguardanti in particolar modo la Lucania.
Storie di piccola borghesia nelle pagine iniziali del Cristo
Authors: Guaragnella Pasquale
Published: November 2016

Il confino al quale Carlo Levi fu condannato nei territori della Lucania, in particolare ad Aliano, gli diede occasione di conoscere molto da vicino le mentalità e i costumi della piccola borghesia meridionale del Ventennio fascista. Attraverso la descrizione dei personaggi più rilevanti del Cristo si è fermato a Eboli, come per esempio il podestà Don Luigi, il dottor Gibilisco e il dottor Milillo per citarne alcuni, Levi opererà una denuncia acre del ruolo della piccola borghesia, una denuncia che si protrarrà con l’ Orologio e susciterà scandalo nella cultura comunista del secondo dopoguerra. L’orientamento di Levi affonda le sue radici nella posizione in particolare di Gaetano Salvemini e di Piero Gobetti.

Il contributo critico che si propone affronta queste tematiche attraversando le pagine iniziali del Cristo.
Egemonie e resistenze: Uno sguardo antropologico sui rapporti tra governi e contadini
Authors: Davis John
Published: November 2016

Il saggio analizza le speciali modalità attraverso le quali i contadini oppongono resistenza allo Stato per reagire alle sue incomprensioni, talvolta anche attraverso giochi di parole. Ugualmente, viene contestata l’arcaicità della civiltà contadina per metterne viceversa in evidenza caratteri che risalgono ad epoca moderna, collocabili all’incirca a inizio di Ottocento. Questi caratteri furono la risposta ai cambiamenti profondi portati dai nuovi borghesi affermatisi con l’eversione della feudalità; si può dire che essi vengono meno negli anni sessanta del Novecento con l’accesso ai nuovi mercati europei. I contadini respingono i piani calati dall’alto e perciò vengono definiti arcaici e ostili alla modernizzazione.
La pittura moderna di Carlo Levi
Authors: Ragozzino Marta
Published: November 2016

Il saggio si estende come una biografia intellettuale che intreccia il percorso pittorico con gli eventi storico-politici, compresa la cospirazione antifascista del Movimento di Giustizia e Libertà all’interno del quale Levi godeva di un carisma naturale. L’esperienza pittorica di Levi viene sviscerata nelle varie fasi con riferimento, tra l’altro, alle antiche suggestioni di Casorati, al sodalizio nel Gruppo dei Sei, al ruolo di Persico e Venturi e di poi alla “conversione” che il confino in Lucania favorisce e configura come punto di arrivo importante nella evoluzione artistica sotto forma di peculiare “realismo umano”. Nel secondo dopoguerra la letteratura prende il sopravvento insieme alla critica e alla teoria politica, la pittura in certo modo involve dopo aver visto l’acme della maturità tra il 1929 e il 1936.
Il processo a Scotellaro
Authors: Porcari Michele
Published: November 2016

Alla luce dell’incartamento superstite viene chiarita la vicenda giudiziaria che portò Scotellaro in carcere a Matera per più di quaranta giorni; fu, come espicitato nella Requisitoria del Procuratore Generale, un chiaro disegno di vendetta politica inteso a bruciare il giovane Sindaco socialista che tanto consenso riscuoteva tra i contadini, in quanto divenuto portavoce autentico delle loro rivendicazioni. Le trame del processo vengono illuminate nel particolare contesto politico-sociale della ricostruzione in Italia all’indomani della seconda guerra mondiale.
αSMA-Expressing Perivascular Cells Represent Dental Pulp Progenitors In Vivo
Authors: Vidovic I. , Banerjee A. , Fatahi R. , Matthews B.G. , Dyment N.A. , Kalajzic I. , Mina M.
Published: November 2016

The goal of this study was to examine the contribution of perivascular cells to odontoblasts during the development, growth, and repair of dentin using mouse molars as a model. We used an inducible, Cre-loxP in vivo fate-mapping approach to examine the contributions of the descendants of cells expressing the αSMA-CreERT2 transgene to the odontoblast lineage. In vivo lineage-tracing experiments in molars showed the contribution of αSMA-tdTomato+ cells to a small number of newly formed odontoblasts during primary dentinogenesis. Using an experimental pulp exposure model in molars to induce reparative dentinogenesis, we demonstrate the contribution of αSMA-tdTomato+ cells to cells secreting reparative dentin. Our results demonstrate that αSMA-tdTomato+ cells differentiated into Col2.3-GFP+ cells composed of both Dspp+ odontoblasts and Bsp+ osteoblasts. Our findings identify a population of mesenchymal progenitor cells capable of giving rise to a second generation of odontoblasts during reparative dentinogenesis. This population also makes a small contribution to odontoblasts during primary dentinogenesis.