bluuebunny/crossref_metadata_2025 huggingface dataset:
Proanthocyanidins as a Potential Novel Way for the Treatment of Hemangioma
Authors: Tang Ran , Xian Dehai , Xu Jixiang , Peng Huiling , Pan Shihong , Zhong Jianqiao
Published: January 2021

Hemangioma, the most common benign vascular tumor, not only affects the appearance and psychology but also has a life‐threatening potential. It is considered that clonal vascular endothelial cell proliferation and excessive angiogenesis are responsible for hemangioma pathogenesis, in which abnormal cytokines/pathways are closely implicated, primarily including high expression of hypoxia‐inducible factor‐1α (HIF‐1α) and vascular endothelial growth factor (VEGF) as well as their downstream pathways, especially phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (Akt). These further stimulate the migration and proliferation of vascular endothelial cells and promote the formation of new vessels, ultimately leading to the occurrence and development of hemangioma. Proanthocyanidins are naturally active substance from plants and fruits. They possess multiple functions like antiproliferation, antiangiogenesis, and antitumor. It has been demonstrated that proanthocyanidins effectively work in various diseases via inhibiting the expression of various factors, e.g., HIF‐1α, VEGF, PI3K, and Akt. Considering the pathogenesis of hemangioma and the effect of proanthocyanidins, we hold a hypothesis that proanthocyanidins would be applied in hemangioma via downregulating cytokine/pathway expression, suppressing vascular cell proliferation and arrest abnormal angiogenesis. Taken together, proanthocyanidins may be a potential novel way for the treatment of hemangioma.
Rupture Risk Assessment of Cervical Spinal Manipulations on Carotid Atherosclerotic Plaque by a 3D Fluid‐Structure Interaction Model
Authors: Chen Yili , Zhang Shaoqun , Chen Yang , Lao Yonghua , Huang Xuecheng , Huang Xiaoyu , Liao Qiming , Li Yikai
Published: January 2021

Object. Use a fluid‐structure interaction (FSI) model to do a safety risk assessment of cervical spinal manipulative therapy (cSMT) for atherosclerosis to study the biomechanical changes of atherosclerosis plaque and the carotid artery (CA) lumen during the process of cSMT. Method. The FSI model, based on MRI data of an atherosclerosis patient, was used to simulate the deformations of the plaque and lumen during the process of two kinds of typical cSMT (the high‐speed, low‐amplitude spinal manipulation and the cervical rotatory manipulation). The biomechanical parameters were recorded, such as the highest wall shear stress (WSS), the maximum plaque wall stress (PWS), the wall tensile stress (Von mises stress, VWTS), and the strain. Result. The max_WSS was 33.77 kPa in the most extensive deformation. The highest WSS region on the plaque surface was also the highest PWS region. The max_PWS in a 12% stretch was 55.11 kPa, which was lower than the rupture threshold. The max_VWTS of the cap in 12% stretch which approached the fracture stress level was 116.75 kPa. Moreover, the vessel’s max_VWTS values in 10% and 12% stretch were 554.21 and 855.19 kPa. They were higher than the fracture threshold, which might cause media fracture. Meanwhile, the 7% stretched strain was 0.29, closed to the smallest experimental green strains at rupture. Conclusion. The carotid arteries’ higher stretch generated the higher stress level of the plaque. Cervical rotatory manipulation might cause plaque at a high risk of rupture in deformation after 12% stretch and more. Lower deformation of the plaque and artery caused by the high‐speed, low‐amplitude spinal manipulation might be safer.
Influence of Immediate Implant Placement and Provisionalization with or without Soft Tissue Augmentation on Hard and Soft Tissues in the Esthetic Zone: A One‐Year Retrospective Study
Authors: De Angelis Paolo , Manicone Paolo Francesco , Gasparini Giulio , De Angelis Silvio , Liguori Margherita Giorgia , De Filippis Ilaria , D’Addona Antonio
Published: January 2021

The purpose of this clinical research was to evaluate peri‐implant marginal changes around immediate implants placed either with the application of SCTG or XCM or without soft tissue grafting. A total of 48 patients requiring a single implant‐supported restoration in the anterior jaw were selected for inclusion. Three surgical procedures were performed, as follows: type 1 implant with subepithelial connective tissue graft (SCTG), type 1 implant with xenogenic collagen matrix (XCM), and type 1 implant without soft tissue augmentation (NG) (control group). The marginal change of peri‐implant soft tissue, facial soft tissue thickness (FSTT), peri‐implant health status, esthetics, and patient satisfaction were assessed at one year after surgery. All of the placed implants showed a survival rate of 100%. No significant differences in FSTT were recorded between the SCTG group and the XCM group after treatment (P > 0.05), while the NG group presented a significant difference (P < 0.05). Patients in the NG group lost significantly more in the buccal marginal level than did patients in the SCTG group and those in the XCM group (P < 0.05). The favourable success rate recorded in all groups confirmed immediate tooth replacement as a choice of treatment for a missing anterior single tooth. The NG group presented significant changes of FSTT and buccal marginal level, while XCM constituted a viable alternative to SCTG.
The Effects of Age, Period, and Cohort on the Mortality of Cervical Cancer in Three High‐Income Countries: Canada, Korea, and Italy
Authors: Wang Jinyao , Bai Zhiqiang , Gao Xudong , Zhang Nianping , Wang Zhenkun
Published: January 2021

Background. As the second most common gynecologic cancer worldwide, cervical cancer has led to morbidity and mortality in thousands of women. Our study is aimed at comparing the long‐term trends of mortality rates for cervical cancer in three high‐income countries—Canada, Korea, and Italy—and analyzing the detached effects of chronological age, time period, and birth cohort by age‐period‐cohort (APC) analysis. Methods. Joinpoint regression was used in this study, and the age‐period‐cohort model combined with the intrinsic estimator method was also applied to estimate the detached effect of each age, time period, and birth cohort on cervical cancer mortality. Results. For the overall trends of ASMRs for cervical cancer, the rates for Canada and Italy generally decreased during the whole observation periods while the rate for Korea exhibited a significant increase from 1986 to 2003. The APC analysis suggested that the cancer mortality risks consistently increased with age in the age groups including women aged 20 to 50 years in all areas. The period effect exhibited a general upward trend for both Korea and Italy, while a decreased trend was observed for Canada during the whole observation period. The mortality risk generally decreased with birth cohort, except there was a slight increase for younger generations in the three countries. Conclusions. Our study shows that the overall decrease in the cohort effect may have contributed to the reduced mortality rate for Italy and Canada, and the increased period effects and cohort effect in younger generations may have led to the increase in cancer mortality rate for Korea.
Effects of Remimazolam and Propofol on Ca2+ Regulation by Ryanodine Receptor 1 with Malignant Hyperthermia Mutation
Authors: Watanabe Tomoyuki , Miyoshi Hirotsugu , Noda Yuko , Narasaki Soshi , Morio Atsushi , Toyota Yukari , Kimura Hiroshi , Mukaida Keiko , Yasuda Toshimichi , Tsutsumi Yasuo M.
Published: January 2021

Background. We investigated the potential safety of remimazolam and propofol in malignant hyperthermia‐ (HM‐) susceptible patients using ryanodine receptor 1‐ (RYR1‐) expressing human embryonic kidney‐ (HEK‐) 293 cells. Methods. We compared the enhanced responsiveness of HEK‐293 cells expressing wild‐type RYR1 with that of mutant RYR1 to caffeine following perfusion with remimazolam or propofol. Furthermore, we investigated whether RYR1 enhanced the responsiveness of cells to remimazolam or propofol and compared the median effective concentration (EC50; i.e., the concentration required to reach half‐maximal activation) using an unpaired two‐tailed t‐test while a P < 0.05 was considered significant. Results. Remimazolam and propofol did not promote the caffeine‐induced increase in intracellular Ca2+ levels in HEK‐293 cells expressing mutant RYR1 even with exposure to approximately 100‐fold the clinically used concentration. In wild‐type RYR1, EC50 values of remimazolam following refusion vs. nonperfusion were 2.86 mM vs. 2.75 mM (P = 0.76) while for propofol perfusion vs. nonperfusion, they were 2.76 mM vs. 2.75 mM, respectively (P = 0.83). In mutant RYR1, EC50 values of remimazolam refusion vs. nonperfusion were 1.58 mM vs. 1.71 mM, respectively (P = 0.63) while for propofol perfusion vs. nonperfusion, they were 1.65 mM vs. 1.71 mM, respectively (P = 0.73). Remimazolam and propofol increased intracellular Ca2+ levels in a concentration‐dependent manner, but the effect was not enhanced by RYR1. EC50 values of remimazolam with non‐RYR1 vs. wild‐type RYR1 were 1.00 mM vs. 0.92 mM, respectively (P = 0.91) while those of propofol were 1.09 mM vs. 1.05 mM, respectively (P = 0.84). Conclusions. The increase in intracellular Ca2+ concentration caused by remimazolam or propofol was not considered an RYR1‐mediated reaction. We conclude that remimazolam and propofol can be safely used as an anesthetic in MH‐susceptible patients with RYR1‐mutation without causing MH and may be safely substituted for an MH‐triggering anesthetic when RYR1‐mediated MH occurs.
Protective Role of a New Polysaccharide Extracted from Lonicera japonica Thunb in Mice with Ulcerative Colitis Induced by Dextran Sulphate Sodium
Authors: Zhou Xiaonan , Lu Qingqing , Kang Xiaozhen , Tian Geng , Ming Deguo , Yang Jialiang
Published: January 2021

Lonicera japonica Thunb is a traditional Chinese herbal medicine for treating intestinal inflammation. The extraction method of Lonicera japonica Thunb polysaccharide (LJP) has been developed previously by our research group. In this study, a Fourier transform infrared spectrometer (FT‐IR) was used to perform a qualitative analysis of LJP and a precolumn derivatization high‐performance liquid chromatography (HPLC) ((Palo Alto, CA, USA) method was used to explore the monosaccharide composition of LJP. Then, we studied the effect of LJP on the intestinal flora and immune functions of dextran sulfate sodium‐ (DSS‐) induced colitis ulcerative mouse models. The results showed that LJP was consisted of 6 types of monosaccharides and had the characteristic absorption of typical polysaccharides. LJP can increase significantly the weight, organ index, serum cytokines (interleukin, tumor necrosis factor, and interferon‐γ), secretory immunoglobulin A (SIgA) concentration, and natural killer (NK) cell and cytotoxic lymphocyte (CTL) activities in DSS‐treated mice. The results of intestinal flora showed that a high dose (150 mg kg-1) of LJP had the best effects on improving the intestinal probiotics (Bifidobacterium and Lactobacilli) and antagonizing the pathogenic bacteria (Escherichia coli and Enterococcus). In addition, the measurement results of the spleen lymphocyte apoptosis confirmed from another perspective that LJP had protective effects of immune cells for DSS‐treated mice.
Enhanced Arsenic Removal from Aqueous Solution by Fe/Mn-C Layered Double Hydroxide Composite
Authors: Wang Yaru , Gao Yingying , Zhu Zongqiang , Zhang Lihao , Zhao Ningning , Fang Yali , Zhu Yinian , Liu Guifeng
Published: January 2021

A novel material named Fe/Mn-C layered double hydroxide composite (Fe/Mn-C-LDH) was synthesized to remove arsenic from an aqueous solution. The removal performance of the composite toward arsenic ions was studied through the batch experiments. The experiment results showed that Fe/Mn-C-LDH exhibited a high adsorption capacity of 46.47 mg/g for As(III) and 37.84 mg/g for As(V) at 318 K, respectively. In addition, the investigation of the release of Fe3+ and Mn2+ in the process of arsenic adsorption revealed that the Fe/Mn-C-LDH exhibited better stability than Fe/Mn-layer double hydroxide (Fe/Mn-LDH) with fewer Mn2+ and Fe3+ releasing under the same condition. The BET results showed that the specific surface area of Fe/Mn-C-LDH decreased after adsorption of As (III) and As (V). Furthermore, the Density Functional Theory (DFT) calculation results proved that the adsorbent combining arsenic by T-site to produce a better adsorption effect for arsenic. Possessing better stability and adsorption capacity, Fe/Mn-C-LDH could potentially serve as a perfect adsorbent for arsenic removal from an aqueous environment. It would provide a promising approach for removing heavy metal from the aquatic environment in the future.
Relationship of PD‐1 (PDCD1) and PD‐L1 (CD274) Single Nucleotide Polymorphisms with Polycystic Ovary Syndrome
Authors: Han Rui , Gong Xiaoyun , Zhu Yuejie , Liu Xiaoran , Xia Yan , Huang Yuhong , Zhang Meng , Zhang Yunian , La Xiaolin , Ding Jianbing
Published: January 2021

This study is to investigate the relationship of programmed cell death 1 (PD‐1; also known as PDCD1) and programmed death‐1‐ligand 1 (PD‐L1; also known as CD274) single nucleotide polymorphisms (SNPs) with polycystic ovary syndrome (PCOS). This study enrolled 330 PCOS patients and 350 matched controls. ELISA was used to detect the PD‐1 and PD‐L1 levels in serum. SnaPshot genotyping was performed to analyze the PD‐1 and PD‐L1 genotyping. Linkage disequilibrium and haplotype of TagSNP loci of PD‐1 and PD‐L1 genes were also detected. The relationship of genotypes and alleles with PCOS was analyzed. The levels of PD‐1 and PD‐L1 in the serum of PCOS patients were significantly lower than those in the control group (P < 0.01). The haplotype TT of PD‐1 gene at rs10204525 and rs7421861 loci was significantly lower in the PCOS group than in the control group (P < 0.001, OR = 0.67, and 95%CI = 0.54‐0.84). PD‐L1 gene SNP loci rs2282055, rs2890658, rs10125854, and rs702275 had linkage disequilibrium. The haplotypes TAAA, GAAC, GAGC, GCAA, and TCGA of PD‐L1 gene SNP loci were significantly higher in PCOS patients than in the control group, whereas haplotypes GAAA, TAAC, TCAA, GCGA, GCAC, and TCGC of PD‐L1 gene SNP loci were significantly lower in PCOS patients than in the control group. PD‐1 and PD‐L1 SNPs may be related to the pathogenesis of PCOS. PD‐1 gene SNP loci rs10204525 and rs7421861 and PD‐L1 gene SNP loci rs2282055, rs2890658, rs10125854, and rs702275 may be new candidate polymorphic loci for PCOS.
Nicotinamide Supplementation Attenuates Renal Interstitial Fibrosis via Boosting the Activity of Sirtuins
Authors: Zhen Xin , Zhang Shaowu , Xie Feifei , Zhou Miaomiao , Hu Zheng , Zhu Fengxin , Nie Jing
Published: January 2021

Background: Progressive tubulointerstitial fibrosis (TIF) is the final common pathway leading to ESRD. There is an urgent need to develop effective approaches slowing the progression of TIF. Previous studies showed that systemic supplementation of nicotinamide (NAM) increases renal NAD+ and reverses ischemic-reperfusion induced acute renal injury. However, the role and mechanism of NAM in TIF has been unclear. Methods: In vivo, we injected NAM (0.25 mg/g) 3 days before unilateral ureter obstruction (UUO) till day 7 post-operation. In vitro, mouse primary proximal tubular epithelial cells (PTCs), rat renal NRK-49F cells, and human renal proximal tubular epithelial cell (HK-2) were pretreated with the indicated concentration of NAM 1 h before incubation with transform growth factor-β1 (TGF-β1) or aristolochic acid (AA) for 24 or 48 h. To evaluate the role of sirtuins (SIRTs), PTCs were pretreated with EX527 or resveratrol 30 min before incubation with NAM and TGF-β1. Results: In the present study, we demonstrated that NAM supplementation prevented UUO-induced TIF, and AA-induced renal injury. NAM also decreased the expression of pro-fibrotic proteins and pro-inflammatory cytokines (IL-6 and TNF-α) and attenuated interstitial inflammation. In vitro experiment showed that, NAM inhibited AA-induced G2/M arrest of HK-2 cells by downregulating the expression of cyclin G1, a target gene of p53. In addition, NAM inhibited TGF-β1-induced fibroblast proliferation and activation shown as downregulated expression of collagen I, fibronectin, PCNA, cyclin D1, IL-6, and TNF-α. NAM decreased the acetylation of Smad3 and p53. EX527, an inhibitor of SIRT1, reversed the effect of NAM on TGF-β1-induced matrix protein production. However, resveratrol, a SIRT1 activator, did not further boost the protective effect of NAM on reducing matrix protein production. Conclusions: Taken together, these data indicate that NAM supplementation could inhibit TIF at least partially by boosting the activity of sirtuins.
Evaluation of Alitretinoin for the Treatment of Mycosis Fungoides and Sézary Syndrome
Authors: Alhusayen Raed , Vu Trang Tuyet , Almuhanna Nouf , Wohlmuth-Wieser Iris , Hardin Jori , Hughes John-Douglas Matthew , Chia Justin , Street Leslie , Shear Neil Hartley , Walsh Scott Richard , Gniadecki Robert
Published: January 2021

Background: Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphoma (CTCL). There is currently no cure for CTCL, and treatment is aimed at limiting disease progression. This study evaluated the efficacy and tolerability of alitretinoin in CTCL management. Methods: A retrospective, multicenter study was conducted on CTCL patients treated with alitretinoin as a primary agent or in combination with standard therapies. Results: Forty-eight patients with MF (n = 40) and SS (n = 8) with a median age of 59.7 years (±14.3) were eligible for study inclusion. Treatment response data were evaluated in 40 patients and safety in 42 patients. 40.0% of the patients had early-stage, 43.8% had advanced-stage CTCL, and in 16.7% of patients there was insufficient information for staging. 40.0% (16/40) of the patients achieved a complete or partial response, whereas 47.5% (19/40) achieved stable disease, 12.5% (5/40) had progressive disease, and there were no cases of disease relapses in responders. Both early and advanced stages of CTCL were responsive to alitretinoin as a primary or combined modality. Alitretinoin was well tolerated, and 64.3% (27/42) of patients did not report any side effects. The most commonly observed side effect was hypertriglyceridemia. Conclusions: This retrospective analysis supports the efficacy and safety of alitretinoin in clearing skin disease and preventing disease progression in CTCL as a monotherapy or in combination with standard therapies.
Pharmacological Treatment of Severe Breathing Abnormalities in a Case of HNRNPU Epileptic Encephalopathy
Authors: Spagnoli Carlotta , Rizzi Susanna , Salerno Grazia Gabriella , Frattini Daniele , Koskenvuo Juha , Fusco Carlo
Published: January 2021

Abnormal breathing patterns are a typical feature of Rett and Pitt-Hopkins syndrome and their variants. Their treatment can be challenging, with a risk of long-term detrimental consequences. Early infantile epileptic encephalopathy (EIEE) type 54 is a rare epileptic encephalopathy caused by pathogenic variants in the heterogeneous nuclear ribonucleoprotein U (HNRNPU) gene. Only one case has been described in the literature with episodes of hyperventilation and apnea, but treatment was not discussed. We describe the clinical and genetic features and treatment strategies in a case of EIEE type 54 and severely abnormal breathing pattern. A novel and likely pathogenic c.2277dup, p.(Pro760Serfs*5) variant in the HNRNPU gene was found in a male patient with severe episodes of hyperventilation and apnea, leading to syncope. Combination therapy with acetazolamide, alprazolam and aripiprazole led to significant clinical improvement. Although HNRNPU has not been implicated in breathing control, pathogenic variants in this gene can be associated with the development of abnormal breathing patterns reminiscent of Rett and Pitt-Hopkins syndrome. Its function as a gene expression regulator and its interaction with transcription factors offers a potential pathogenetic link between these 3 disorders. Based on our experience, treatment strategies can be similar to those already applied for patients with Pitt-Hopkins and Rett syndrome.
Elevation of Urate in Saliva and Serum of Patients with Knee Osteoarthritis
Authors: Mirzaii-Dizgah Mohammad-Reza , Mirzaii-Dizgah Mohammad-Hossein , Mirzaii-Dizgah Iraj
Published: January 2021

Background: Knee osteoarthritis (knee OA) is the most common joint disease and the leading cause of disability and has a considerable financial burden on the healthcare system. Objective: The aim of the present study was to evaluate urate in saliva and serum of knee OA. Methods: Serum and saliva urate levels of 30 knee OA and 30 healthy controls were evaluated in a cross-sectional study. Data were analysed by Student’s t test, Pearson correlation test, and receiver operating characteristic. Results: The mean serum and both stimulated and unstimulated saliva urate levels were higher in the knee OA than that of the healthy group. WOMAC score positively correlated with serum (r = 0.485; p = 0.004), unstimulated saliva (r = 0.575; p = 0.001) and stimulated saliva (r = 0.453; p = 0.009) levels of urate. The serum level of urate significantly correlated with unstimulated (r = 0.442; p < 0.001) and stimulated (r = 0.563; p < 0.001) saliva urate levels. Serum and saliva urate had significant cutoff values (6.4, 4.9, and 3.3 mg/dL in serum, stimulated, and unstimulated saliva, respectively). Conclusion: In this study, urate in serum and saliva was increased in patients with knee OA and positively correlated with WOMAC.
False Negativity of Targeted Axillary Dissection in Breast Cancer
Authors: Kirkilesis George , Constantinidou Anastasia , Kontos Michalis
Published: January 2021

Introduction: Targeted axillary dissection (TAD) has been proposed as an alternative method for the staging of patients with node-positive breast cancer who undergo neoadjuvant chemotherapy. However, not much is known yet about the false-negative rate (FNR) of the method and the subsequent risk of underestimation of residual axillary disease. Methods: This study reviews published articles with calculations of false negativity of TAD and potential factors that may influence it. Results: The FNR of TAD is usually reported as being <10%, but this calculation is usually based on small study populations. Lower FNR is a common finding along with lower N status, while not enough data are available yet for greater axillary involvement. When a marked node is revealed to be a sentinel lymph node (SLN) at surgery after neoadjuvant chemotherapy (NAC), this seems to be another factor that contributes to reliable TAD. With regard to the methods used to mark the positive node before chemotherapy and retrieval at surgery, there is no clear advantage of one over the other. The availability of relevant resources, the costs, and local legislation must all be taken into account for the selection of the optimal strategy. Conclusion: Although still in its early days, the FNR of TAD can be low, at least in patients with relatively little axillary involvement and when the marked node is the SLN. All reported methods of lymph node marking seem reliable.
Atopische Dermatitis: Kombination aus Dupilumab und Kortikosteroid auch bei 6- bis 11-Jährigen erfolgreich
Authors: Fölster-Holst Regina
Published: January 2021

Background: Children with severe atopic dermatitis (AD) have limited treatment options. Objective: We report the efficacy and safety of dupilumab + topical corticosteroids (TCS) in children aged 6–11 years with severe AD inadequately controlled with topical therapies. Methods: In this double-blind, 16-week, phase 3 trial (NCT03345914), 367 patients were randomized 1:1:1 to 300 mg dupilumab every 4 weeks (300 mg q4w), a weight-based regimen of dupilumab every 2 weeks (100 mg q2w, baseline weight <30 kg; 200 mg q2w, baseline weight ≥30 kg), or placebo; with concomitant medium-potency TCS. Results: Both the q4w and q2w dupilumab + TCS regimens resulted in clinically meaningful and statistically significant improvement in signs, symptoms, and quality of life (QOL) versus placebo + TCS in all prespecified endpoints. For q4w, q2w, and placebo, 32.8%, 29.5%, and 11.4% of patients, respectively, achieved Investigator’s Global Assessment scores of 0 or 1; 69.7%, 67.2%, and 26.8% achieved ≥75% improvement in Eczema Area and Severity Index scores; and 50.8%, 58.3%, and 12.3% achieved ≥4-point reduction in worst itch score. Response to therapy was weight-dependent: optimal dupilumab doses for efficacy and safety were 300 mg q4w in children <30 kg and 200 mg q2w in children ≥30 kg. Conjunctivitis and injection-site reactions were more common with dupilumab + TCS than with placebo + TCS. Limitations: Short-term 16-week treatment period; severe AD only. Conclusion: Dupilumab + TCS is efficacious and well tolerated in children with severe AD, significantly improving signs, symptoms, and QOL.
Helicobacter pylori Infection in Children with Concurrent Celiac Disease and Type 1 Diabetes Mellitus
Authors: Bayrak Nevzat Aykut , Volkan Burcu
Published: January 2021

Objectives: Data regarding Helicobacter pylori (Hp) infection frequency in concurrent celiac disease (CD) and type 1 diabetes mellitus (T1DM) (CD + T1DM) are anecdotal. This study aimed to evaluate the association between Hp and concomitant CD + T1DM in children. Methods: In this 2-center, case-control study, children who underwent esophago-gastro-duodenoscopy (EGD) were studied. CD diagnosis was established by favorable histology and serology. Hp infection was confirmed by both histology and the rapid urease test. Patients were divided into 3 groups as CD only (CDo), CD + T1DM, and non-CD children who underwent endoscopy as controls. Results: Among the 1,431 EGDs performed, 783 cases were eligible. Overall, 215 cases had CDo (mean age: 9.12 ± 4.18 years, 58.1% girls), 63 cases had CD + T1DM (mean age: 9.29 ± 4.46 years, 50.8% girls), and 505 cases were controls (mean age: 9.69 ± 4.52 years, 56.6% girls). Hp infection rate was significantly lower in CD + T1DM group (controls: 49.7% vs. CDo: 32.1% vs. CD + T1DM: 20.6%, p < 0.01). After adjustment for age, gender, and socioeconomic status, the Hp infection rate was still significantly low (adjusted odds ratio [aOR]: 1.57, 95% confidence interval (CI): 1.35–1.83, p < 0.01). A difference in Hp infection rate between controls and CDo group (aOR: 1.43, 95% CI: 1.09–2.12, p < 0.05), and between CDo and CD + T1DM (aOR: 0.89, 95% CI: 0.65–1.54, p < 0.05) group was significant. The severity of duodenal lesions and the presence of Hp infection were not correlated in all celiac children (r: 0.113, p > 0.05). Conclusion: The frequency of Hp infection was significantly lower in CD + T1DM children, compared to the CDo group and the controls.
Co-Medication and Nutrition in Hepatocellular Carcinoma: Potentially Preventative Strategies in Hepatocellular Carcinoma
Authors: Kusnik Alexander , Hunter Nicole , Rasbach Erik , Miethke Thomas , Reissfelder Christoph , Ebert Matthias Philip , Teufel Andreas
Published: January 2021

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, with about 841,000 new cases and 782,000 deaths annually. Given the clearly defined population at risk, mostly patients with liver cirrhosis, prevention of HCC could be highly effective. Summary: Besides regular ultrasound surveillance, numerous publications have suggested protective effects of diverse drugs and nutrients. However, none of those preventive options has made it into clinical routine or practice guidelines. We therefore summarize the current status of preventive effects of drugs such as statins, acetylsalicylic acid (ASA), and metformin, but also dietary aspects and nutrients such as coffee, tea, and vitamin D supplementation. A successful implementation of some of these strategies may potentially lead to improved prevention of HCC development in patients with liver cirrhosis. Key Messages: Accumulating data suggest that particularly ASA, antidiabetic therapies, and statins may substantially decrease HCC incidence in patients at risk.
Dietary Fibers and Proteins Modulate Behavior via the Activation of Intestinal Gluconeogenesis
Authors: Sinet Flore , Soty Maud , Zemdegs Juliane , Guiard Bruno , Estrada Judith , Malleret Gaël , Silva Marine , Mithieux Gilles , Gautier-Stein Amandine
Published: January 2021

Introduction: Several studies have suggested that diet, especially the one enriched in microbiota-fermented fibers or fat, regulates behavior. The underlying mechanisms are currently unknown. We previously reported that certain macronutrients (fermentable fiber and protein) regulate energy homeostasis via the activation of intestinal gluconeogenesis (IGN), which generates a neural signal to the brain. We hypothesized that these nutriments might control behavior using the same gut-brain circuit. Methods: Wild-type and IGN-deficient mice were fed chow or diets enriched in protein or fiber. Changes in their behavior were assessed using suited tests. Hippocampal neurogenesis, extracellular levels of serotonin, and protein expression levels were assessed by immunofluorescence, in vivo dialysis, and Western blotting, respectively. IGN was rescued by infusing glucose into the portal vein of IGN-deficient mice. Results: We show here that both fiber- and protein-enriched diets exert beneficial actions on anxiety-like and depressive-like behaviors. These benefits do not occur in mice lacking IGN. Consistently, IGN-deficient mice display hallmarks of depressive-like disorders, including decreased hippocampal neurogenesis, basal hyperactivity, and deregulation of the hypothalamic-pituitary-adrenal axis, which are associated with increased expression of the precursor of corticotropin-releasing hormone in the hypothalamus and decreased expression of the glucocorticoid receptor in the hippocampus. These neurobiological alterations are corrected by portal glucose infusion mimicking IGN. Conclusion: IGN translates nutritional information, allowing the brain to finely coordinate energy metabolism and behavior.
dramaturgo é um fingidor, finge tão completamente que...
Authors: Corradin Flavia Maria , Rosa Carlos Gontijo , Silva Rosely de Fátima , Simas Mônica Muniz de Souza , Poma Paola
Published: January 2021

Editorial do número 23 da Revista Desassossego. Dossiê "Fingimento na dramaturgia"
Perspectivas feministas sobre a perseguição de bruxaria em "O crime de Aldeia Velha", de Bernardo Santareno
Authors: Driver Robin
Published: January 2021

Inspirada no caso verídico da queimada-viva de Soalhães, a peça O crime de Aldeia Velha (1959), de Bernardo Santareno, encena a perseguição de uma jovem pelas mulheres da comunidade rural em que vive. Acusada de ser uma bruxa possessa do diabo, Joana acabará por morrer numa fogueira supostamente acendida na esperança de a livrar do mal. No presente estudo, objetiva-se analisar essa obra à luz de teorias feministas levantadas sobretudo a partir dos anos 60 do século passado acerca da perseguição das bruxas, a fim de identificar tanto pontos de contato entre estas últimas e a peça de Santareno, quanto particularidades na visão do dramaturgo português no que toca às questões de gênero que subjazem a supostos casos de bruxaria. Especial atenção será concedida às implicações específicas do cenário da peça de Santareno – uma aldeia portuguesa nos meados do século XX – no sentido em que diverge sensivelmente do foco das teorias mencionadas acima, que, na maior parte, foram desenvolvidas na Europa do norte e nos Estudos Unidos, e que incidem prioritariamente sobre a proliferação de processos de bruxas nessas regiões nos primeiros séculos da Idade Moderna.
Current Indications for Transcatheter Mitral Valve Replacement Using Transcatheter Aortic Valves
Authors: Urena Marina , Vahanian Alec , Brochet Eric , Ducrocq Gregory , Iung Bernard , Himbert Dominique
Published: January 2021

Use of transcatheter mitral valve replacement (TMVR) using transcatheter aortic valves in clinical practice is limited to patients with failing bioprostheses and rings or mitral valve disease associated with severe mitral annulus calcification. Whereas the use of valve-in-valve TMVR appears to be a reasonable alternative to surgery in patients at high surgical risk, much less evidence supports valve-in-ring and valve-in-mitral annulus calcification interventions. Data on the results of TMVR in these settings are derived from small case series or voluntary registries. This review summarizes the current evidence on TMVR using transcatheter aortic valves in clinical practice from the characteristics of the TMVR candidates, screening process, performance of the procedure, and description of current results and future perspectives. TMVR using dedicated devices in native noncalcified mitral valve diseases is beyond the scope of the article.
Supine Parasympathetic Withdrawal and Upright Sympathetic Activation Underly Abnormalities of the Baroreflex in Postural Tachycardia Syndrome
Authors: Stewart Julian M. , Warsy Irfan A. , Visintainer Paul , Terilli Courtney , Medow Marvin S.
Published: January 2021

Upright postural tachycardia syndrome (POTS) resembles hemorrhage with reduced central blood volume, parasympathetic withdrawal, and sympathetic activation. Baroreflex dysfunction causes low heart rate variability, enhanced blood pressure variability, and decreased maximum baroreflex gain (G
max
) putatively measured by spontaneous fluctuation of blood pressure and heart rate. We investigated whether/how cardiovagal baroreflex in POTS differ from control, supine, and upright by comparing indices of spontaneous baroreflex function to that measured using the reference standard modified Oxford method. This uses sodium nitroprusside and phenylephrine to generate the sigmoidal cardiovagal baroreflex curve. Baroreflex in POTS was evaluated supine and upright untreated and then treated to determine whether pyridostigmine or digoxin (a vagotonic agent) corrects baroreflex deficits. Supine, G
max
was reduced by 25% in POTS compared with controls, and descriptors of this sigmoidal relationship showed a reduction, downward shift, and left shift of the response to the pharmacological decrease and increase in blood pressure. Digoxin normalized supine cardiovagal baroreflex while pyridostigmine resulted in partial normalization as G
max
, and other descriptors of these relationships were similar to control. Upright, cardiovagal curves were distorted and displaced in untreated POTS, while digoxin and pyridostigmine left shifted the cardiovagal curves due to sympathetic activity. Cardiovagal baroreflex deficits in POTS relate to parasympathetic withdrawal while supine, remediated completely by digoxin, and sympathetic activation upright through alteration of baroreflex responsivity. Since these baroreflex effects resemble those measured following microgravity/chronic bedrest, vagotonic/sympatholytic treatment combined with aerobic exercise might normalize the cardiovagal baroreflex and provide therapeutic benefit in patients with POTS.
Association of Blood Pressure Variability and Diuretics With Cardiovascular Events in Patients With Chronic Kidney Disease Stages 1–5
Authors: Gregg L. Parker , Hedayati S. Susan , Yang Hui , Van Buren Peter N. , Banerjee Subhash , Navaneethan Sankar D. , Virani Salim S. , Winkelmayer Wolfgang C. , Alvarez Carlos A.
Published: January 2021

Visit-to-visit blood pressure variability (BPV) is associated with cardiovascular events in the general population. Data are scarce in chronic kidney disease. We hypothesized that BPV would be associated with cardiovascular outcomes, death, and end-stage kidney disease (ESKD) and that diuretics would modify these associations in patients with chronic kidney disease. We studied US Veterans with nondialysis chronic kidney disease stages 1–5 and hypertension on nondiuretic antihypertensive monotherapy. At the time of second antihypertensive agent prescription, we propensity-matched for exposure to a loop or thiazide diuretic versus any other antihypertensive. BPV was defined as the coefficient of variation of systolic blood pressure over 6 months after second agent prescription. Cox proportional hazards regression measured associations of BPV with a primary cardiovascular event composite (fatal or nonfatal myocardial infarction or ischemic stroke; heart failure hospitalization). Secondary outcomes included all-cause death, each primary outcome component, end-stage kidney disease, and cardiovascular death. There were 31 394 participants in each group. BPV was associated with composite cardiovascular events, hazard ratio (95% CI) at second, third, fourth, and fifth versus first quintile: 1.79 (1.53–2.11), 2.32 (1.99–2.71), 2.60 (2.24–3.02), and 3.12 (2.68–3.62). Diuretics attenuated associations between the fourth and fifth BPV quintiles with composite events (
P
interaction
=0.03 and 0.04, respectively). BPV was associated with all secondary outcomes except end-stage kidney disease, with no diuretic interactions. BPV was associated with cardiovascular events and death but not end-stage kidney disease in patients with chronic kidney disease, with attenuated associations with cardiovascular events in the diuretic-treated group at high BPV quintiles. Future studies should investigate whether other antihypertensive classes modify these risks.
Antihypertensive Drugs and COVID-19 Risk
Authors: Semenzato Laura , Botton Jérémie , Drouin Jérôme , Baricault Bérangère , Vabre Clémentine , Cuenot François , Penso Laetitia , Herlemont Philippe , Sbidian Emilie , Weill Alain , Dray-Spira Rosemary , Zureik Mahmoud
Published: January 2021

After initially hypothesizing a positive relationship between use of renin-angiotensin-aldosterone system inhibitors and risk of coronavirus disease 2019 (COVID-19), more recent evidence suggests negative associations. We examined whether COVID-19 risk differs according to antihypertensive drug class in patients treated by ACE (angiotensin-converting enzyme) inhibitors and angiotensin receptor blockers (ARBs) compared with calcium channel blockers (CCBs). Three exclusive cohorts of prevalent ACE inhibitors, ARB and CCB users, aged 18 to 80 years, from the French National Health Insurance databases were followed from February 15, 2020 to June 7, 2020. We excluded patients with a history of diabetes, known cardiovascular disease, chronic renal failure, or chronic respiratory disease during the previous 5 years, to only consider patients treated for uncomplicated hypertension and to limit indication bias. The primary end point was time to hospitalization for COVID-19. The secondary end point was time to intubation/death during a hospital stay for COVID-19. In a population of almost 2 million hypertensive patients (ACE inhibitors: 566 023; ARB: 958 227; CCB: 358 306) followed for 16 weeks, 2338 were hospitalized and 526 died or were intubated for COVID-19. ACE inhibitors and ARBs were associated with a lower risk of COVID-19 hospitalization compared with CCBs (hazard ratio, 0.74 [95% CI, 0.65–0.83] and 0.84 [0.76–0.93], respectively) and a lower risk of intubation/death. Risks were slightly lower for ACE inhibitor users than for ARB users. This large observational study may suggest a lower COVID-19 risk in hypertensive patients treated over a long period with ACE inhibitors or ARBs compared with CCBs. These results, if confirmed, tend to contradict previous hypotheses and raise new hypotheses.
Body Mass Index and Clinical Outcomes in Asian Patients With Atrial Fibrillation Receiving Oral Anticoagulation
Authors: Lee So-Ryoung , Choi Eue-Keun , Jung Jin-Hyung , Park Sang-Hyun , Han Kyung-Do , Oh Seil , Lip Gregory Y.H.
Published: January 2021

Background and Purpose:

The influence of body mass index (BMI) on clinical outcomes in patients with atrial fibrillation remains controversial, especially among Asians. We aimed to evaluate the association between BMI and clinical outcomes in Asian patients with atrial fibrillation receiving oral anticoagulants.

Methods:

Using the Korean National Health Insurance database between January 2015 and December 2017, we identified oral anticoagulant new users among patients with nonvalvular atrial fibrillation who had BMI information. We analyzed ischemic stroke, intracranial hemorrhage, hospitalization for gastrointestinal bleeding, major bleeding, all-cause death, and the composite clinical outcome according to BMI categories.

Results:

A total of 43 173 patients were included across BMI categories (kg/m
2
): underweight (<18.5) in 3%, normal (18.5 to <23) in 28%, overweight (23 to <25) in 24%, obese I (25 to <30) in 39%, and obese II (≥30) in 6%. Higher BMI (per 5 kg/m
2
increase) was significantly associated with lower risks of ischemic stroke (hazard ratio [HR], 0.891 [95% CI, 0.801–0.992]), hospitalization for gastrointestinal bleeding (HR, 0.785 [95% CI, 0.658–0.937]), major bleeding (HR, 0.794 [95% CI, 0.686–0.919]), all-cause death (HR, 0.658 [95% CI, 0.605–0.716]), and the composite clinical outcome (HR, 0.751 [95% CI, 0.706–0.799]), except for intracranial hemorrhage (HR, 0.815 [95% CI, 0.627–1.061]). The underweight group was associated with an increased risk of composite clinical outcome (HR, 1.398 [95% CI, 1.170–1.671]), mainly driven by an increased risk of all-cause death. The effects of non–vitamin K antagonist oral anticoagulant versus warfarin on clinical outcomes were similar across BMI groups.

Conclusions:

Higher BMI was independently associated with a lower risk of ischemic stroke, major bleeding, and better survival. Underweight patients had a higher risk of all-cause death and composite clinical outcome. The optimal BMI for patients with atrial fibrillation should be defined and managed according to an integrated care pathway.
Associations of an Abnormal Physiological Score With Outcomes in Acute Intracerebral Hemorrhage
Authors: Song Lili , Wang Xia , Ouyang Menglu , Sun Lingli , Chen Xiaoying , Arima Hisatomi , Sandset Else C. , Delcourt Candice , Wang Jiguang , Chen Guofang , Robinson Thompson , Lindley Richard I. , Chalmers John , Anderson Craig S. ,   for the INTERACT2 Investigators
Published: January 2021

Background and Purpose:

We determined associations of physiological abnormalities (systolic blood pressure, glucose, and body temperature) and warfarin use with outcomes in spontaneous intracerebral hemorrhage.

Methods:

Post hoc analyses of INTERACT2 (Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial) comparing systolic blood pressure control (<140 versus <180 mm Hg) in 2839 hypertensive patients with intracerebral hemorrhage (onset <6 hours). Multivariable logistic regression defined associations of baseline scores assigned as 0 to 6 per 10 mm Hg systolic blood pressure increase (range, 150–220 mm Hg) and 0 or 1 for serum glucose (≤6.5 versus >6.5 mmol/L), body temperature (≤37.5 °C versus >37.5 °C), and warfarin use (no versus yes) and death or major disability (modified Rankin Scale scores 3–6 at 90 days).

Results:

Baseline score distribution was 0 (7.7%), 1 (15.6%), 2 (19.0%), 3 (19.1%), 4 (15.2%), 5 (11.6%), 6 (8.9%), and 7 (2.9%). After adjustment for baseline neurological severity and potential confounders, significant linear associations were evident for increasing (per point) score and death or major disability (odds ratio, 1.12 [95% CI, 1.07–1.17]), death (odds ratio, 1.15 [95% CI, 1.07–1.23]), and major disability (odds ratio, 1.10 [95% CI, 1.05–1.15]).

Conclusions:

Combination of abnormal physiological parameters and warfarin use is associated with poor outcomes in intracerebral hemorrhage. Effects of their early control is under investigation in INTERACT3 (Intensive Care Bundle With Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial).

Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT00716079.
Cost-Effectiveness of Mechanical Thrombectomy for Treatment of Nonminor Ischemic Stroke Across Europe
Authors: Candio Paolo , Violato Mara , Leal Jose , Luengo-Fernandez Ramon
Published: January 2021

Background and Purpose:

Mechanical thrombectomy (MT) has been recommended for the treatment of nonminor ischemic stroke by national and international guidelines, but cost-effectiveness evidence has been generated for only a few countries using heterogeneous evaluation methods. We estimate the cost-effectiveness of MT across 32 European countries.

Methods:

A Markov model was developed to estimate the cost-effectiveness of MT compared with standard care over a 5-year time horizon. Patients with ischemic stroke eligible for MT were identified from 2017 country-specific incidence data. A societal perspective was adopted, including health, social, and informal care costs, and productivity losses. Model outcomes were expressed as quality-adjusted life years. Sensitivity analyses were conducted to test the robustness of findings.

Results:

We identified 267 514 ischemic stroke cases that were eligible for MT treatment across 32 European countries. MT was found to be more effective and cheaper than standard care in two-thirds of the countries (21/32) and cost-effective in all but one country (Bulgaria). Across Europe, the intervention was estimated to produce over 101 327 additional quality-adjusted life years (95% uncertainty interval, 65 180–149 085) and cost savings of $981 million (€868 million, 95% uncertainty interval, −1544 to 2564) and of $1.7 billion (€1.5 billion, 95% uncertainty interval, −1.2 to 3.6) in health and social care and societal costs, respectively.

Conclusions:

MT is highly likely to be cost-effective compared with standard care across Europe as a whole and in the vast majority of European countries.