bluuebunny/crossref_metadata_2025 huggingface dataset:
Transgelin 2 Promotes Paclitaxel Resistance, Migration, and Invasion of Breast Cancer by Directly Interacting with PTEN and Activating PI3K/Akt/GSK-3β Pathway
Authors: Liu Leichao , Meng Ti , Zheng Xiaowei , Liu Yang , Hao Ruifang , Yan Yan , Chen Siying , You Haisheng , Xing Jianfeng , Dong Yalin
Published: September 2019

MDR and tumor migration and invasion are still the main obstacles to effective breast cancer chemotherapies. Transgelin 2 has recently been shown to induce drug resistance, tumor migration, and invasion. The aim of this study was to determine the biological functions of Transgelin 2 and the mechanism underlying how Transgelin 2 induces paclitaxel (PTX) resistance and the migration and invasion of breast cancer. We detected that the protein level of Transgelin 2 was significantly upregulated in breast cancer tissues compared with adjacent nontumor tissues. A bioinformatics analysis indicated that Transgelin 2 was significantly related to clinicopathologic parameters and patient prognosis. Overexpression of Transgelin 2 enhanced the migration and invasion of human breast cancer cells and decreased the sensitivity of breast cancer cells to paclitaxel. Meanwhile, the tumorigenesis and metastasis of breast cancer cells were also enhanced by Transgelin 2 overexpression in vivo. Moreover, Transgelin 2 overexpression activated the PI3K/Akt/GSK-3β pathway by increasing the phosphorylation levels of Akt and GSK-3β and decreasing the expression of PTEN. We also found that Transgelin 2 could directly interact with PTEN and was located upstream of PTEN. Furthermore, the PI3K/Akt pathway inhibitor MK-2206 reversed the resistance to paclitaxel and inhibited the migration and invasion of breast cancer cells. These findings indicate that Transgelin 2 promotes paclitaxel resistance and the migration and invasion of breast cancer by directly interacting with PTEN and activating the PI3K/Akt/GSK-3β pathway. Transgelin 2 may therefore be useful as a novel biomarker and therapeutic target for breast cancer.
Risk Factors for Post-Endoscopic Retrograde Pancreatography Pancreatitis: A Retrospective Chart Review in a Regional Hospital in Japan
Authors: Shimamura Takuya , Miyahara Koichi , Takamori Ayako , Hidaka Hidenori , Ito Yoichiro , Fujimoto Shun , Takedomi Hironobu , Tsuruoka Nanae , Sakata Yasuhisa , Eguchi Yuichiro , Node Koichi , Noda Takahiro , Fujimoto Kazuma
Published: September 2019

Background: Endoscopic retrograde pancreatography (ERCP) is sometimes complicated by post-ERCP pancreatitis (PEP), which is a severe adverse effect. Objective: The present study was performed to (i) evaluate the risk factors for PEP and (ii) compare the risk of PEP after ERCP performed in the off hours versus regular hours. Methods: This retrospective study included 374 patients who underwent ERCP from January 2013 to December 2017. Among these patients, 38 (10.2%) developed PEP. The potential risk factors for PEP were evaluated by multivariate regression analysis, and the risk of PEP was compared between ERCP performed during regular hours and off hours. Results: The independent risk factors for PEP were a relatively younger age (<75 years; p = 0.024), female sex (p = 0.002), a history of pancreatitis (p = 0.044), and performance of pancreatography (p = 0.010). Use of a diclofenac suppository and performance of pancreatic stenting were not preventive for PEP after ERCP. The complication rate of PEP did not differ between ERCP performed during the off hours versus regular hours. Conclusions: A relatively younger age (<75 years), female sex, a history of pancreatitis, and performance of pancreatography were potential risk factors for PEP, whereas the risk of PEP was not different between ERCP performed during the off hours versus regular hours.
Could Residents Adequately Assess the Severity of Hidradenitis Suppurativa? Interrater and Intrarater Reliability Assessment of Major Scoring Systems
Authors: Włodarek Katarzyna , Stefaniak Aleksandra , Matusiak Łukasz , Szepietowski Jacek C.
Published: September 2019

A wide variety of assessment tools have been proposed for hidradenitis suppurativa (HS) until now, but none of them meets the criteria for an ideal score. Because there is no gold standard scoring system, the choice of the measure instrument depends on the purpose of use and even on the physician’s experience in the subject of HS. The aim of this study was to assess the intrarater and interrater reliability of 6 scoring systems commonly used for grading severity of HS: the Hurley Staging System, the Refined Hurley Staging, the Hidradenitis Suppurativa Severity Score System (IHS4), the Hidradenitis Suppurativa Severity Index (HSSI), the Sartorius Hidradenitis Suppurativa Score and the Hidradenitis Suppurativa Physician’s Global Assessment Scale (HS-PGA). On the scoring day, 9 HS patients underwent a physical examination and disease severity assessment by a group of 16 dermatology residents using all evaluated instruments. Then, intrarater reliability was calculated using intraclass correlation coefficient (ICC), and interrater variability was evaluated using the coefficient of variation (CV). In all 6 scorings the ICCs were >0.75, indicating high intrarater reliability of all presented scales. The study has also demonstrated moderate agreement between raters in most of the evaluated measure instruments. The most reproducible methods, according to CVs, seem to be the Hurley staging, IHS4, and HSSI. None of the 6 evaluated scoring systems showed a significant advantage over the other when comparing ICCs, and all the instruments seem to be very reliable methods. The interrater reliability was usually good, but the most repeatable results between researchers were obtained for the easiest scales, including Hurley scoring, IHS4 and HSSI.
Mechanosensitive Pathways Involved in Cardiovascular Development and Homeostasis in Zebrafish
Authors: Li Rongsong , Baek Kyung In , Chang Chih-Chiang , Zhou Bill , Hsiai Tzung K.
Published: September 2019

Cardiovascular diseases such as coronary heart disease, myocardial infarction, and cardiac arrhythmia are the leading causes of morbidity and mortality in developed countries and are steadily increasing in developing countries. Fundamental mechanistic studies at the molecular, cellular, and animal model levels are critical for the diagnosis and treatment of these diseases. Despite being phylogenetically distant from humans, zebrafish share remarkable similarity in the genetics and electrophysiology of the cardiovascular system. In the last 2 decades, the development and deployment of innovative genetic manipulation techniques greatly facilitated the application of zebrafish as an animal model for studying basic biology and diseases. Hemodynamic shear stress is intimately involved in vascular development and homeostasis. The critical mechanosensitive signaling pathways in cardiovascular development and pathophysiology previously studied in mammals have been recapitulated in zebrafish. In this short article, we reviewed recent knowledge about the role of mechanosensitive pathways such as Notch, PKCε/PFKFB3, and Wnt/Ang2 in cardiovas­cular development and homeostasis from studies in the ­zebrafish model.
MR Navigation and Tractography-Assisted Transcranial Neuroendoscopic Aspiration of Pediatric Thalamic Abscess
Authors: Ozgural Onur , Al-Beyati Eyyub S.M. , Kahilogullari Gokmen
Published: September 2019

Aim: Management of thalamic abscess is being considered as a contentious issue in neurosurgery. Regarding these lesions, besides removing the abscess, the most minimal morbidity is targeted during surgery and planning. Material and Method: A 5-year-old female presented with the symptoms of altered consciousness and left hemiparesis. Her medical history pointed out that she was being followed up for a congenital cardiac anomaly consisting of transposition of the great arteries and a ventricular septal defect. A cranial MRI revealed 2 masses with peripheral contrast enhancement in the right frontal and thalamic regions. She was operated immediately and the right frontal mass, compatible with abscess, was totally excised with frontal mini craniotomy. The patient was hospitalized and followed up under intensive parenteral antibiotics. Control cranial imaging revealed progression in the size of the thalamic abscess, which was corroborative with the increased left hemiparesis. MR tractography was obtained and the patient underwent MR navigation and tractography combined neuronavigation-assisted transcranial neuroendoscopic aspiration of the thalamic abscess. Results: The patient was stable in the early and late postoperative periods and her hemiparesis showed a dramatic recovery with no additional neurological deficits. Conclusion: Neuronavigation is considered as one of the techniques that aid the neurosurgeon to augment the success of surgery and minimize the morbidity, especially in critically localized lesions, i.e., eloquent areas. Combining MR navigation with MR tractography images and using them during neuronavigation to assist endoscopic procedures may decrease the surgical morbidity as much as possible.
Cardiorespiratory Physiology following Minimally Invasive Surfactant Therapy in Preterm Infants
Authors: Sehgal Arvind , Bhatia Risha , Roberts Calum T.
Published: September 2019

Introduction: Surfactant replacement therapy through the endotracheal tube has been shown to improve lung compliance and reduce pulmonary pressures. Minimally invasive surfactant therapy (MIST) combines the benefits of continuous positive airway pressure (CPAP) and surfactant for spontaneously breathing preterm infants. We aimed to characterize the haemodynamic changes accompanying the first dose of MIST in preterm infants. Methods: Poractant alfa (200 mg/kg) was administered as MIST while on CPAP support. Echocardiograms were performed before (T1) and 30 (T2) and 60 min (T3) after MIST to assess serial change. Results: Twenty infants (mean gestational age 29.5 ± 2.8 weeks, median birth weight 1,102 g, IQR 840–1,940) received MIST at a median age of 16 h (IQR 3–24). FiO2 decreased significantly at 30 min (0.41 ± 0.08 to 0.27 ± 0.03, p < 0.001). Significant changes were noted at T2 for ductal parameters (decreased % time right to left shunt: 25% [15–33] to 14.5% [6–22], p = 0.013). Reduced pulmonary vascular resistance (PVR; increased pulmonary artery time velocity ratio 0.23 ± 0.05 to 0.28 ± 0.04 ms, p = 0.004) and improved longitudinal (tricuspid annular plane systolic excursion 4.5 ± 0.8 to 5.3 ± 0.9 mm, p = 0.004) and global (fractional area change 25 ± 2.3 vs. 27 ± 2%, p = 0.002) ventricular function were noted. Conclusions: This is the first study assessing cardiovascular adaptation to MIST, a procedure fast gaining acceptance in the neonatal community. Increased pulmonary blood flow is likely due to a combined effect of increased ductal flow, reduced PVR, and increased ventricular function.
p16 Expression Correlates with Invasive Ocular Surface Squamous Neoplasms in HIV-Infected Mozambicans
Authors: Carrilho Carla , Miu Chau , Kim Yeji , Karki Susan , Balmaceda Alexandra , Challa Bindu , Diamond Scott , Monteiro Eliane , Marole Evelia , Lorenzoni Cesaltina , Zambujo Yolanda , Liu Yu-Tsueng , Schooley Robert T. , Lin Jonathan H.
Published: September 2019

Background: p16 immunohistochemistry is widely used to diagnose human papillomavirus (HPV)-related squamous neoplasms of cervix, anogenital, head, and neck tissues. The incidence of these HPV-related squamous neoplasms is markedly increased in the HIV-infected population. Ocular surface squamous neoplasia (OSSN) is also more common in HIV-infected patients. However, the expression pattern of p16 in OSSN among HIV-infected patients is unclear. Here, we examined the expression of p16 in OSSN surgical excisions collected from a large HIV-infected cohort from ­Mozambique. Methods: OSSN surgical tissue specimens were collected from 75 Mozambican patients. Formalin-fixed, paraffin-embedded tissue blocks from these OSSNs were sectioned, stained with hematoxylin and eosin (H&E), and p16 expression by immunohistochemistry. H&E slides were reviewed to determine if OSSNs were noninvasive conjunctival intraepithelial neoplasms or invasive squamous cell carcinomas (SCC). Cases were classified as p16 positive or negative based on diffuse nuclear and cytoplasmic expression of p16 in neoplastic cells. Results: p16 positivity was found in a minority of OSSN cases (14/75). p16 positivity was significantly associated with the invasive SCC type of OSSN in HIV-infected patients (p value of 0.026). Conclusions: The majority of OSSNs in our HIV-infected cohort do not express p16. However, those cases that are p16-positive are significantly more likely to be the invasive SCC form of OSSN. We propose that p16 expression may identify more aggressive OSSNs in HIV-infected populations.
Association between BDNF Polymorphism and Hypothalamic-Pituitary-Adrenal Activity in Later Adulthood
Authors: Fiocco Alexandra J. , D’Amico Danielle , de Beaumont Louis , Poirier Judes , Lupien Sonia
Published: September 2019

Stress exposure over the lifespan is robustly associated with accelerated cognitive decline in later life. Brain-derived neurotrophic factor (BDNF) is shown to regulate activity of the hypothalamic-pituitary-adrenal axis. The objective of this study was to evaluate the association betweenthe BDNF polymorphism and indices of stress among adults aged 50+. Community-dwelling middle-aged and older adults provided a blood sample for BDNF genotyping. Participants also sampled their saliva 5 times/day for 3 consecutive days for the measurement of diurnal cortisol and underwent the Trier Social Stress Test (TSST) for the measurement of stress reactivity. Among 121 adults aged 50–67 years (78% female; 89% Caucasian), 74 participants were Val/Val carriers and 47 carried 1 copy of the Met allele. Repeated-measures analyses did not reveal an association between BDNF genotype and diurnal salivary cortisol (p = 0.63); however, analyses revealed that Met+ carriers displayed lower levels of cortisol secretion in response to the TSST compared with Val/Val carriers; F(4.43, 496.238) = 2.57, p = 0.032. This is the first study to evaluate the role of the BDNF polymorphism in stress physiology among older adults. Future studies are needed to evaluate the lifespan interconnections between BDNF and stress physiology.
DCR2, a Cellular Senescent Molecule, Is a Novel Marker for Assessing Tubulointerstitial Fibrosis in Patients with Immunoglobulin A Nephropathy
Authors: Chen Jia , Hu Wei , Xiao Fei , Lin Lirong , Chen Kehong , Wang Liming , Wang Xiaoyue , He Yani
Published: September 2019

Background/Aims: Stress-induced cell senescence, which contributes to cell cycle arrest and is independent of age, plays an important role in chronic kidney disease (CKD) progression. DcR2, as a senescent marker, exclusively expressed in senescent tubular epithelia. The objective of this study was to examine whether urinary DcR2 (uDcR2) could be a potential biomarker for tubulointerstitial fibrosis (TIF) in patients with immunoglobulin A nephropathy (IgAN). Methods: This study included 210 IgAN patients and 80 healthy volunteers, with uDcR2 levels measured using enzyme-linked immunosorbent assay. We examined the relationship among uDcR2/Cr levels, renal function, and pathological parameters, using regression analysis to identify risk factors for TIF and the area under the curve (AUC) approach to predict TIF. Renal DcR2 expression was quantified by immunohistochemistry. Co-expression of DcR2 with fibrotic markers (α-smooth muscle actin [α-SMA], collagen III) was analyzed by confocal microscopy. Results: Levels of uDcR2/Cr were significantly higher in IgAN patients and in those with more severe TIF, compared with healthy controls. Serum DcR2 levels were similar across groups. The proportion of IgAN patients with stages 1–2 CKD and T0 was highest among those with uDcR2/Cr <130 ng/g. In contrast, the majority of those with uDcR2/Cr >201 ng/g had stages 4–5 CKD and T2. Levels of uDcR2/Cr were positively associated with urinary albumin to creatinine ratio (ACR), urinary N-acetyl-β-D-glucosaminidase (uNAG)/Cr, and TIF scores and negatively associated with estimated glomerular filtration rate (eGFR). uDcR2/Cr, uNAG, ACR, and eGFR were independent predictors for TIF, with AUC of 0.907 for uDcR2/Cr. This AUC value was higher than that observed for eGFR, uNAG/Cr, or ACR. The sensitivity and specificity of uDcR2/Cr in predicting TIF were 87.0 and 80.5%, respectively. Moreover, uDcR2/Cr levels were positively associated with the percentage of renal DcR2 expression. Renal DcR2 co-localized with α-SMA and collagen III in the kidneys of IgAN patients. Conclusions: Levels of uDcR2/Cr were closely associated with the severity of TIF and renal function parameters. uDcR2/Cr represents a potential biomarker for predicting TIF in IgAN patients.
Functional Outcomes and Quality of Life in Elderly Patients after Restorative Proctocolectomy for Ulcerative Colitis
Authors: Minagawa Tomohiro , Ikeuchi Hiroki , Kuwahara Ryuichi , Horio Yuki , Sasaki Hirofumi , Chohno Teruhiro , Bando Toshihiro , Uchino Motoi
Published: September 2019

Background/Aim: Ileal pouch anal anastomosis (IPAA) has become the surgical procedure of choice for patients with ulcerative colitis (UC). However, to date few studies have examined functional outcomes or quality of life (QOL) in elderly patients after pouch construction. Methods: In December 2017, we sent questionnaires to 224 patients aged 65 years and older at the time who underwent an IPAA at our hospital between June 1987 and May 2015 regarding issues related to QOL and functional outcomes. Responders aged 65–69 years old were defined as the elderly group (EG), while those 70 years old and over comprised the super-EG (SEG). Results: The response rate was 60.7% (136/224); 70 patients were classified as EG, and 66 were classified as SEG. The SEG were older at the time of the IPAA and during the follow-up period (p < 0.01). The stool frequency per day was 8 times in both groups (p = 0.21). There was no significant difference between the EG and SEG with regard to daytime (53 vs. 56%, p = 0.73) or nighttime (65.7 vs. 53%, p = 0.16) soiling. There was also no difference in the exacerbation of daytime or nighttime soiling compared to the first year after the operation (daytime 5.7 vs. 12.1%, p = 0.23; nighttime 7.1 vs. 9.1%, p = 0.76). QOL was evaluated using the modified fecal incontinence QOL (mFIQL) scale, with no significant difference between the EG and SEG (27 vs. 31 points). Since both groups had mFIQL scores <50, QOL was considered to be maintained. Conclusion: In our analysis of elderly patients in the long-term period following surgery for UC, some noted fecal soiling, though QOL was largely maintained, and there were no serious effects on daily life.
A Narrative Review of Lifestyle Factors Associated with Parkinson’s Disease Risk and Progression
Authors: Nag Nupur , Jelinek George A.
Published: September 2019

Parkinson’s disease is a complex slowly progressive neurodegenerative disorder with motor and non-motor symptoms affecting daily living. Despite effective symptomatic treatments, with various degrees of side effects, no disease-modifying therapeutic options presently exist. Symptoms progress, with an accumulating burden, reducing the quality of life and forming the impression that medications are no longer effective. Adopting positive lifestyle behaviours can empower patients, improve the quality of life, alleviate symptoms, and potentially slow disease progression. Lifestyle behaviours including nutrition, cognitive enrichment, physical activity, and stress management have beneficial effects on brain health and quality of life. While some evidence of an association of lifestyle with Parkinson’s disease risk and progression exists, the sparse and often conflicting data make it difficult to provide clinical recommendations. Herein, we highlight studies showing promising associations between lifestyle and Parkinson’s disease. Given the increasing aging of populations worldwide and the prevalence of neurological disorders, further research into self-management through adoption of positive lifestyle behaviours is clearly warranted to better enable individualized care.
NIV NAVA versus Nasal CPAP in Premature Infants: A Randomized Clinical Trial
Authors: Kallio Merja , Mahlman Mari , Koskela Ulla , Aikio Outi , Suo-Palosaari Maria , Pokka Tytti , Saarela Timo , Hallman Mikko
Published: September 2019

Background: Noninvasive ventilation is recommended for neonatal respiratory distress to avoid adverse effects of invasive ventilation. Objective: The aim of this study was to compare the feasibility of noninvasive neurally adjusted ventilatory assist (NIV NAVA) and continuous positive airway pressure (CPAP) in preterm newborn infants. Methods: Forty preterm infants (gestational age 28+0 to 36+6 weeks) requiring CPAP and supplemental oxygen (FiO2 >0.23) for respiratory distress at <48 h of postnatal age were randomized to NIV NAVA or CPAP. The primary endpoint was the inspired oxygen concentration 12 h after study inclusion. Secondary endpoints were the duration of oxygen treatment, total duration of respiratory support, parenteral nutrition, blood gas values, patient comfort, need for invasive ventilation, and treatment complications. Results: The mean FiO2 at the time of study inclusion was 0.29 in both groups. After 12 h of treatment, FiO2 was 0.26 ± 0.07 and 0.26 ± 0.04 in the NIV NAVA and CPAP groups, respectively (difference 0.006, 95% CI –0.4 to 0.5), with no difference between the groups during the course of noninvasive ventilation (p = 0.80). Seven patients (35%) in the NIV NAVA group and 10 (50%) in the control group required intubation (difference 15%, 95% CI –15.5 to 4.3, p = 0.36). Time to intubation, gas exchange, vital parameters, pain scale, treatment complications, and neonatal outcome did not differ between the groups. Conclusions: In the present trial, NIV NAVA had no statistically significant effect on oxygen requirements or the need for invasive ventilation in preterm newborn infants.
Evaluation of Lower Extremities’ Vascular Characteristics in Myelomeningocele Patients: A Case-Control Study
Authors: Salari Farhad , Golpayegani Mehdi , Habibi Zohreh , Yaghoubi Shahin , Anbarlouei Mousarreza , Mehdizadeh Mehrzad , Nejat Farideh
Published: September 2019

Objective: Myelomeningocele (MMC) is the most common neural tube defect. Patients with MMC have multiple risk factors for venous thrombosis, but this complication rarely occurs. This lower rate of venous thrombosis in MMC children could be related to some characteristics of the vessels in the lower extremities. This study aimed at finding explanations for this dilemma. Methods: A case-control study was designed in the Children’s Hospital Medical Center, Tehran considering paraplegic patients with MMC as the case group and nonparaplegic MMC patients as a control group. Doppler ultrasound was performed to evaluate femoral and popliteal arterial and venous properties. Results: Patients aged from 8 months to 12 years were evaluated. The mean diameter of the femoral arteries was 3.73 ± 0.23 and 4.72 ± 0.39 mm among paraplegic and nonparaplegic MMC patients, respectively (p = 0.02). The femoral artery flow was 0.52 ± 0.08 and 0.75 ± 0.06 L/min, respectively in the case and control groups (p = 0.015). The diameters of the femoral veins were 4.85 ± 0.34 and 5.13 ± 0.32 mm in the case and control groups, respectively (p > 0.05). Besides, the blood flows of the case and control groups’ femoral veins were 0.27 ± 0.08 and 0.14 ± 0.01 L/min, respectively (p = 0.6). It turned out that lower extremities’ arteries in the case group had significantly lower blood flow and diameter compared to those of the control group. However, the same venous properties did not show any significant differences. Conclusion: The decreased arterial flow along with the unchanged venous properties leads to less stasis and better drainage of the blood, which in turn might result in a lower incidence of deep vein thrombosis.
Chronic Kidney Disease in Children Aged 6–15 Years and Associated Risk Factors in Apizaco, Tlaxcala, Mexico, a Pilot Study
Authors: Ortega-Romero Manolo , Méndez-Hernández Pablo , Cruz-Angulo María del Carmen , Hernández-Sánchez Ana María , Álvarez-Elías Ana Catalina , Muñoz-Arizpe Ricardo , Sales-Heredia Francisco , Aguilar-Madrid Guadalupe , Juárez-Perez Cuauhtémoc Arturo , Soto Virgilia , Valadés Teresa , Olvera-Rivas Nadia , Obrador-Vera Gregorio T. , Barbier Olivier C. , Medeiros Mara
Published: September 2019

Introduction: Tlaxcala, a small state in central Mexico, has the highest prevalence of chronic kidney disease (CKD) deaths in population aged 5–14 in Mexico, most of them with unknown etiology. Objective: To determine the prevalence of CKD in apparently healthy pediatric population in Apizaco, Tlaxcala. Methods: A cross-sectional pilot study was carried out in children deemed as healthy; subjects with previous diagnosis of CKD were excluded. Informed consent was obtained in all cases. A physical examination was performed, a questionnaire was applied. Blood and urine samples were obtained for serum creatinine, urinalysis, and microalbumin/creatinine ratio. A second and third evaluation was performed after 6 and 18 months in those found with urinary anomalies/CKD to confirm the diagnosis. Results: One hundred and nine subjects completed physical examination, which are the biological samples. Median age was 12 years. CKD stage 2 was confirmed in 5 subjects in the sixth month confirmation visit (4.6%). One patient accepted renal biopsy and Alport Syndrome was found. In a robust multivariate analysis, the risk factors related to reduction in the glomerular filtration rate were males –5.15 mL/min/1.73 m2 (p = 0.002), older participants as by –1.58 mL/min/1.73 m2 per year (p < 0.0001), and among participants living close to a river –3.76 mL/min/1.73 m2 (p = 0.033). Discussion/Conclusion: The prevalence of CKD in the population studied in Apizaco Tlaxcala was confirmed in 4.6 cases per 100 inhabitants between 6 and 15 years. Males, older age, and living close to a river were the risk predictive factors. More studies are needed to determine the causes of the high CKD prevalence in this population.
Charcot and Cholesterin
Authors: Walusinski Olivier
Published: September 2019

We offer here an observation written in 1866 by Jean-Martin Charcot, accompanied by drawings made during the autopsy of a patient who died of “cerebral softening.” Focusing mainly on French medical progress at the time, our survey of the state of knowledge of cerebrovascular pathology indicates that Charcot completely explained the pathophysiology of cerebral infarction, describing the ulceration of an atheromatous plaque at the intima of an artery, on which a clot aggregates, blocks the vessel, or releases embolus downstream, causing cerebral ischemia and parenchymal lesions. Using the term “cholestérine” (cholesterin), the name of cholesterol at the time, he identified the biological nature of atheromatous plaques, and made detailed drawings. This observation, included in the famous thesis of Ivan Poumeau, indicates that Charcot did not neglect cerebrovascular pathology, ischemic in this case, but also pathology caused by hemorrhaging, as in the thesis of Charles Bouchard. This interest, which we see clearly during his first decade at Hôpital de la Salpêtrière, gradually turned toward other neurological pathologies that ensured his fame as a founder of neurology more enduringly and overshadowed the conceptual advances he made in the vascular domain.
Donepezil Treatment for Alzheimer’s Disease in Chronic Dialysis Patients
Authors: Yiannopoulou Konstantina G. , Anastasiou Aikaterini I. , Kyrozis Andreas , Anastasiou Ioannis P.
Published: September 2019

Donepezil is one of the cholinesterase inhibitors that are indicated for the treatment of mild to moderate Alzheimer’s disease (AD). Pharmacokinetic analysis has shown that donepezil is primarily eliminated by renal excretion rather than biliary excretion in humans. Therefore, patients with impaired renal function are at high risk of toxicity caused by accumulation of this drug. It is also well known that dialysis patients have very often cholinergic disorders. On the other hand, with the increasing number of long-term chronic dialysis patients, the prevalence of cognitive disorders is increasing in elderly dialysis patients. Because of the above-mentioned special risks of these patients, acetylcholinesterase inhibitors, such as donepezil, are avoided to be prescribed for them. We studied 5 cases of chronic hemodialysis outpatients (3 men [70, 72, and 86 years old] and 2 women [65 and 71 years old]) who were diagnosed as having moderate AD. We administered donepezil at 2.5 mg/day orally to the patients. After 1 month’s treatment, their behavioral symptoms were improved, without them having any adverse events. We enhanced the dose to 5 mg/day without the patients experiencing any episodes of drug toxicity. After 3 months of treatment with the higher dose, their cognitive and executive functions were slightly improved and their behavioral disorders were remarkably milder, without them experiencing any episodes of drug toxicity. The patients’ condition remained stable for 6 months after the initial administration of the drug. All of them were followed for the 10 following years, showing a mild cognitive decline per year for the first 5 years and more severe decline for the remaining years of the follow-up. Our cases indicate that donepezil treatment under prudent use may be well tolerated and have a beneficial impact on chronic hemodialysis patients with AD.
The Significance of Galectin-1 and Galectin-9 Expression in Endometrial Carcinoma
Authors: Sun Xiao-fei , Dai Shu-yan
Published: September 2019

Objectives: To explore the expression of Galectin-1 and -9 and clinicopathological features in endometrial carcinoma (EC). Methods: Normal endometrium (NE), atypical endometrial hyperplasia (AH), and endometrial cancer were collected, and immunohistochemistry was used to detect the expression of Galectin-1 and -9 in all specimens in the same condition. Results: The positive rate of Galectin-1 expression in NE, AH, and endometrial cancer was 30, 70, and 90.2%. The positive rate of Galectin-9 expression in them was 20, 75, and 78.4%, respectively. The expression of Galectin-1 and -9 in the EC and AH was significantly higher than that in the NE (p< 0.05). However, there was no significant difference between the EC and the AH (p > 0.05). The expression of Galectin-1 in endometrial adenocarcinoma was significantly different among tissues of different histological grades, pathological stages, degrees of myometrial infiltration, or lymph node metastasis (p > 0.05). The expression of Galectin-9 in endometrial adenocarcinoma was significantly different among different historical grades, pathological stages, degrees of myometrial infiltration, and lymph node metastasis (p < 0.05). The expression of Galectin-9 in tissues at an early stage, with the degree of myometrial infiltration <1/2, and without lymph node metastasis, was significantly stronger than in those in the late stage, with a degree of myometrial infiltration ≥1/2 and lymph node metastasis. Conclusion: Both Galectin-1 and -9 were associated with the occurrence of EC and its pathological behavior. High expression of Galectin-1 suggests a poor prognosis, whereas high expression of Galectin-9 was associated with early pathological changes. Galectin-1 and -9 can provide references for early screening and indicate the prognosis of endometrial lesions, which are of great significance for patients’ quality of life.
Peritoneal Carcinomatosis in Gastro-Entero-Pancreatic Neuroendocrine Neoplasms: Clinical Impact and Effectiveness of the Available Therapeutic Options
Authors: Merola Elettra , Prasad Vikas , Pascher Andreas , Pape Ulrich-Frank , Arsenic Ruza , Denecke Timm , Fehrenbach Uli , Wiedenmann Bertram , Pavel Marianne Ellen
Published: September 2019

Background: Peritoneal carcinomatosis (PC) can affect the quality of life of patients with gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs). Peritoneal disease control by medical therapies in these patients has been poorly investigated Objectives: To describe, in a consecutive series of GEP-NENs, the clinical impact of PC and to report the effectiveness of available treatments in PC control. Methods: A retrospective, monocenter analysis was performed of 135 GEP-NENs (1993–2016) with at least a 12-month follow-up. Peritoneal disease progression was defined as detection of a significant increase in size or appearance of new implants by imaging. Results: A total of 62.9% of cases had diffuse PC (involving at least 2 abdominal quadrants). According to WHO 2017 classification, cases were 42.3% neuroendocrine tumors NET-G1, 45.5% NET-G2, 6.5% NET-G3, 4.9% neuroendocrine carcinomas NEC-G3, and 0.8% mixed neuroendocrine-nonneuroendocrine neoplasms. Bowel obstruction occurred in 30 (22.2%) patients mainly depending on size of peritoneal implants (HR: 1.10; 95% CI: 1.02–1.20; p = 0.01). Patients with diffuse PC treated with peptide receptor radionuclide therapy (PRRT) showed peritoneal progression in 37.5% of cases, and bowel obstruction or ascites in 28.1%. Better peritoneal disease control was observed in cases receiving somatostatin analogs at first-line therapy, probably due to a less aggressive disease behavior for these patients. Conclusions: Bowel obstruction is not uncommon in GEP-NENs with PC. PRRT should be adopted with caution in GEP-NENs with diffuse PC, but larger series are needed to confirm these data.
Reflexões iniciais sobre a paratopia criadora na obra “O Grifo de Abdera” de Lourenço Mutarelli
Authors: Doretto Vitoria Ferreira
Published: September 2019

Neste artigo propomos o que chamamos de reflexões iniciais sobre a obra de Lourenço Mutarelli. Fazemos uma breve análise de “O Grifo de Abdera” (Companhia das Letras, 2015), a partir do conceito de paratopia criadora desenvolvido por Dominique Maingueneau (2006), para o estudo do discurso literário dentro da vertente francesa da análise do discurso. Ao analisarmos os três personagens principais desta obra de ficção brasileira, delineamos as três instâncias de autoria (escritor, inscritor e pessoa), tidas como constituintes da ação criadora, em cada um destes personagens. Ao final da análise podemos verificar a possibilidade de realmente entender estes personagens como autores em diferentes estágios.
Haroldo de Campos e a poesia pós-utópica da agoridade
Authors: Bomfim Monalisa Medrado
Published: September 2019

O capitalismo selvagem e predatório e o Estado repressivo e uniformizador caracterizaram o contexto histórico brasileiro após o golpe de 64. Esse cenário, ascende em Haroldo de Campos a necessidade de trazer a produção poética para o agora, para um contemporâneo que não é propriamente um momento pós-moderno, mas antes pós-utópico. Esse trabalho tem como objetivo realizar uma análise do ensaio Poesia e modernidade: da morte da arte à constelação. O poema pós-utópico, de Haroldo de Campos, relacionando-o com o livro Os filhos do barro, de Octávio Paz, o texto Sobre o conceito de história, de Walter Benjamin, e o livro O princípio esperança de Ernst Bloch, de modo a compreender e detalhar os conceitos da poesia pós-utópica. Por fim, esta caraterização visa identificar e ilustrar os traços pós-utópicos expressos na produção poética de Campos, mais especificamente nos poemas o anjo esquerdo da história e dialética do agora – 2, que compõem o livro Crisantempo: no espaço curvo nasce um.
Considerações sobre o trágico e sobre a tradução poética
Authors: Vieira Trajano
Published: September 2019

Considerações sobre o trágico e sobre a tradução poética
Automated and Interpretable Patient ECG Profiles for Disease Detection, Tracking, and Discovery
Authors: Tison Geoffrey H. , Zhang Jeffrey , Delling Francesca N. , Deo Rahul C.
Published: September 2019

Background:

The ECG remains the most widely used diagnostic test for characterization of cardiac structure and electrical activity. We hypothesized that parallel advances in computing power, machine learning algorithms, and availability of large-scale data could substantially expand the clinical inferences derived from the ECG while at the same time preserving interpretability for medical decision-making.

Methods and Results:

We identified 36 186 ECGs from the University of California, San Francisco database that would enable training of models for estimation of cardiac structure or function or detection of disease. We segmented the ECG into standard component waveforms and intervals using a novel combination of convolutional neural networks and hidden Markov models and evaluated this segmentation by comparing resulting electrical intervals against 141 864 measurements produced during the clinical workflow. We then built a patient-level ECG profile, a 725-element feature vector and used this profile to train and interpret machine learning models for examples of cardiac structure (left ventricular mass, left atrial volume, and mitral annulus e-prime) and disease (pulmonary arterial hypertension, hypertrophic cardiomyopathy, cardiac amyloid, and mitral valve prolapse). ECG measurements derived from the convolutional neural network-hidden Markov model segmentation agreed with clinical estimates, with median absolute deviations as a fraction of observed value of 0.6% for heart rate and 4% for QT interval. Models trained using patient-level ECG profiles enabled surprising quantitative estimates of left ventricular mass and mitral annulus e′ velocity (median absolute deviation of 16% and 19%, respectively) with good discrimination for left ventricular hypertrophy and diastolic dysfunction as binary traits. Model performance using our approach for disease detection demonstrated areas under the receiver operating characteristic curve of 0.94 for pulmonary arterial hypertension, 0.91 for hypertrophic cardiomyopathy, 0.86 for cardiac amyloid, and 0.77 for mitral valve prolapse.

Conclusions:

Modern machine learning methods can extend the 12-lead ECG to quantitative applications well beyond its current uses while preserving the transparency that is so fundamental to clinical care.
Severe Cardiac Dysfunction and Death Caused by Arrhythmogenic Right Ventricular Cardiomyopathy Type 5 Are Improved by Inhibition of Glycogen Synthase Kinase-3β
Authors: Padrón-Barthe Laura , Villalba-Orero María , Gómez-Salinero Jesús M. , Domínguez Fernando , Román Marta , Larrasa-Alonso Javier , Ortiz-Sánchez Paula , Martínez Fernando , López-Olañeta Marina , Bonzón-Kulichenko Elena , Vázquez Jesús , Martí-Gómez Carlos , Santiago Demetrio J. , Prados Belén , Giovinazzo Giovanna , Gómez-Gaviro María Victoria , Priori Silvia , Garcia-Pavia Pablo , Lara-Pezzi Enrique
Published: September 2019

Background:

Arrhythmogenic cardiomyopathy/arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiac disease characterized by fibrofatty replacement of the myocardium, resulting in heart failure and sudden cardiac death. The most aggressive arrhythmogenic cardiomyopathy/ARVC subtype is ARVC type 5 (ARVC5), caused by a p.S358L mutation in TMEM43 (transmembrane protein 43). The function and localization of TMEM43 are unknown, as is the mechanism by which the p.S358L mutation causes the disease. Here, we report the characterization of the first transgenic mouse model of ARVC5.

Methods:

We generated transgenic mice overexpressing TMEM43 in either its wild-type or p.S358L mutant (TMEM43-S358L) form in postnatal cardiomyocytes under the control of the α-myosin heavy chain promoter.

Results:

We found that mice expressing TMEM43-S358L recapitulate the human disease and die at a young age. Mutant TMEM43 causes cardiomyocyte death and severe fibrofatty replacement. We also demonstrate that TMEM43 localizes at the nuclear membrane and interacts with emerin and β-actin. TMEM43-S358L shows partial delocalization to the cytoplasm, reduced interaction with emerin and β-actin, and activation of glycogen synthase kinase-3β (GSK3β). Furthermore, we show that targeting cardiac fibrosis has no beneficial effect, whereas overexpression of the calcineurin splice variant calcineurin Aβ1 results in GSK3β inhibition and improved cardiac function and survival. Similarly, treatment of TMEM43 mutant mice with a GSK3β inhibitor improves cardiac function. Finally, human induced pluripotent stem cells bearing the p.S358L mutation also showed contractile dysfunction that was partially restored after GSK3β inhibition.

Conclusions:

Our data provide evidence that TMEM43-S358L leads to sustained cardiomyocyte death and fibrofatty replacement. Overexpression of calcineurin Aβ1 in TMEM43 mutant mice or chemical GSK3β inhibition improves cardiac function and increases mice life span. Our results pave the way toward new therapeutic approaches for ARVC5.
Turmeric, Pepper, Cinnamon, and Saffron Consumption and Mortality
Authors: Hashemian Maryam , Poustchi Hossein , Murphy Gwen , Etemadi Arash , Kamangar Farin , Pourshams Akram , Khoshnia Masoud , Gharavi Abdolsamad , Brennan Paul J. , Boffetta Paolo , Dawsey Sanford M. , Abnet Christian C. , Malekzadeh Reza
Published: September 2019

Background

Previous studies have reported the beneficial effects of spice consumption on lipid profiles, fasting glucose, and blood pressure, which suggests that spice consumption could affect the risk of cardiovascular disease, diabetes mellitus, and consequently mortality. The objective of this study was to evaluate the relationship between consumption of turmeric, black or chili pepper, cinnamon, and saffron with overall and cause‐specific mortality in an adult population in Iran.

Methods and Results

We used data from the Golestan Cohort Study, which has followed 50 045 participants aged 40 to 75 years from baseline (2004–2008). After establishing the exclusion criteria, 44 398 participants were included in the analyses. Spice consumption data were extracted from the baseline Food Frequency Questionnaire. Cox models were used to estimate hazard ratios (
HR
) and 95%
CI
for overall and cause‐specific mortality, comparing the ever consumers to the never consumers as a reference group for each type of spice (adjusted for known and suspected confounders). During 11 years of follow‐up, 5121 people died. Turmeric consumption was associated with significantly reduced risk of overall mortality (
HR
=0.90, 95%
CI
=0.85–0.96) and cardiovascular mortality (
HR
=0.91, 95%
CI
=0.82–0.99). Black or chili pepper consumption was associated with significantly reduced risk of overall mortality (
HR
=0.91, 95%
CI
=0.86–0.98). Saffron consumption was associated with significantly reduced risk of overall (
HR
=0.85, 95%
CI
=0.77–0.94) and cardiovascular mortality (
HR
=0.79, 95%
CI
=0.68–0.92). We found no associations with cinnamon consumption or between any of these spices and cancer mortality.

Conclusions

Consuming turmeric or saffron was associated with decreased risk of overall and cardiovascular mortality. The hypothesis of a protective effect of spice consumption on mortality should be tested in other prospective studies.
Association of Intracranial Aneurysms With Aortic Aneurysms in 125 Patients With Fusiform and 4253 Patients With Saccular Intracranial Aneurysms and Their Family Members and Population Controls
Authors: Kurtelius Arttu , Väntti Nelli , Rezai Jahromi Behnam , Tähtinen Olli , Manninen Hannu , Koskenvuo Juha , Tulamo Riikka , Kotikoski Satu , Nurmonen Heidi , Kämäräinen Olli‐Pekka , Huttunen Terhi , Huttunen Jukka , von und zu Fraunberg Mikael , Koivisto Timo , Jääskeläinen Juha E. , Lindgren Antti E.
Published: September 2019

Background

Varying degrees of co‐occurrence of intracranial aneurysms (
IA
) and aortic aneurysms (
AA
) have been reported. We sought to compare the risk for
AA
in fusiform intracranial aneurysms (
fIA
) and saccular intracranial aneurysms (
sIA
) disease and evaluate possible genetic connection between the
fIA
disease and
AA
s. Additionally, the characteristics and aneurysms of the
fIA
and
sIA
patients were compared.

Methods and Results

The Kuopio Intracranial Aneurysm Database includes all 4253
sIA
and 125
fIA
patients from its Eastern Finnish catchment population, and 13 009 matched population controls and 18 455 first‐degree relatives to the
IA
patients were identified, and the Finnish national registers were used to identify the individuals with
AA
. A total of 33
fIA
patients were studied using an exomic gene panel of 37 genes associated with
AA
s. Seventeen (14.4%)
fIA
patients and 48 (1.2%)
sIA
patients had a diagnosis of
AA
. Both
fIA
and
sIA
patients had
AA
s significantly more often than their controls (1.2% and 0.5%) or relatives (0.9% and 0.3%). In a competing risks Cox regression model, the presence of
fIA
was the strongest risk factor for
AA
(subdistribution hazard ratio 7.6, 95% CI 3.9–14.9,
P
<0.0005). One likely pathogenic variant in

COL
5A2

and 3 variants of unknown significance were identified in

MYH
11

,

COL
11A1

, and

FBN
1

in 4
fIA
patients.

Conclusions

The prevalence of
AA
s is increased slightly in
sIA
patients and significantly in
fIA
patients.
fIA
patients are older and have more comorbid diseases than
sIA
patients but this alone does not explain their clinically significant
AA
risk.
Structural Changes in the African Easterly Jet and Its Role in Mediating the Effects of Saharan Dust on the Linear Dynamics of African Easterly Waves
Authors: Grogan Dustin F. P. , Nathan Terrence R. , Chen Shu-Hua
Published: September 2019

Analytical and numerical analyses are used to examine how structural changes to the African easterly jet (AEJ) mediate the effects of Saharan mineral dust aerosols on the linear dynamics of African easterly waves (AEWs). An analytical expression for the generation of eddy available potential energy (APE) is derived that exposes how the AEJ and dust combine to affect the energetics of the AEWs. The expression is also used to interpret the numerical results, which are obtained by radiatively coupling a simplified version of the Weather Research and Forecasting Model to a conservation equation for dust. The WRF-Dust model is used to conduct linear simulations based on five observationally consistent zonal-mean AEJs: a reference AEJ and four other AEJs that are obtained by perturbing the maximum meridional and vertical shear. For a dust distribution consistent with summertime observations over North Africa, the numerical simulations show the following: (i) Irrespective of the AEJ structure or the zonal scale of the AEWs, the dust increases the growth rates of the AEWs. (ii) The growth rates of the AEWs are optimized when the ratio of baroclinic to barotropic energy conversions is largest. (iii) When the energy conversions are sufficiently large, the zonal scale of the fastest-growing AEW shortens. The numerical results confirm the analytical analysis, which shows that the dust effects, which are modulated by the Doppler-shifted frequency, are strongest north of the AEJ axis, a region where the dust augments the preexisting meridional temperature gradient.