bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting toll‐like receptor 4 signalling pathways: can therapeutics pay the toll for hypertension?
Authors: Nunes Kenia Pedrosa , de Oliveira Amanda Almeida , Mowry Francesca Elisabeth , Biancardi Vinicia Campana 
Published: July 2018

The immune system plays a prominent role in the initiation and maintenance of hypertension. The innate immune system, via toll‐like receptors (TLRs), identifies distinct signatures of invading microbes and damage‐associated molecular patterns and triggers a chain of downstream signalling cascades, leading to secretion of pro‐inflammatory cytokines and shaping the adaptive immune response. Over the past decade, a dysfunctional TLR‐mediated response, particularly via TLR4, has been suggested to support a chronic inflammatory state in hypertension, inducing deleterious local and systemic effects in host cells and tissues and contributing to disease progression. While the underlying mechanisms triggering TLR4 need further research, evidence suggests that sustained elevations in BP disrupt homeostasis, releasing endogenous TLR4 ligands in hypertension. In this review, we discuss the emerging role of TLR4 in the pathogenesis of hypertension and whether targeting this receptor and its signalling pathways could offer a therapeutic strategy for management of this multifaceted disease.Linked ArticlesThis article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc
Novel chemical compound SINCRO with dual function in STING‐type I interferon and tumor cell death pathways
Authors: Kimura Yoshitaka , Negishi Hideo , Matsuda Atsushi , Endo Nobuyasu , Hangai Sho , Inoue Asuka , Nishio Junko , Taniguchi Tadatsugu , Yanai Hideyuki 
Published: July 2018

Recent years have seen a number of regulatory approvals for immune oncology or immunotherapies based on their ability to enhance antitumor immune responses. Nevertheless, the majority of patients remain refractory to these treatments; hence, new therapies that augment current immunotherapies are required. Innate immune receptors that recognize nucleic acids are potent activators of subsequent T‐cell responses and, as a result, can evoke potent antitumor immune responses. Herein, we present a novel compound N‐{3‐[(1,4′‐bipiperidin)‐1′‐yl]propyl}‐6‐[4‐(4‐methylpiperazin‐1‐yl)phenyl]picolinamide (SINCRO; STING‐mediated interferon‐inducing and cytotoxic reagent, original) as an anticancer drug that activates the cytosolic DNA‐sensing STING (stimulator of interferon genes) signaling pathway leading to the induction of type I interferon (IFN) genes. Indeed, IFN‐β gene induction by SINCRO is abolished in STING‐deficient cells. In addition to its IFN‐inducing activity, SINCRO shows STING‐independent cytotoxic activity against cancer cells. SINCRO does not evoke DNA double‐strand break or caspase‐3 cleavage. Thus, SINCRO induces cell death in a method different from conventional apoptosis‐inducing pathways. Finally, we provide evidence that giving SINCRO significantly attenuates in vivo tumor growth by both type I IFN‐dependent and independent mechanisms. Thus, SINCRO is an attractive anticancer compound with dual function in that it evokes type I IFN response to promote antitumor immunity as well as inducing tumor cell death. SINCRO may provide a new platform for the development of drugs for effective cancer therapy.
A retrospective comparative study of venous vs nonringed expanded polytetrafluoroethylene extension grafts for anterior sector outflow reconstruction in right lobe living donor liver transplantation
Authors: Goja Sanjay , Yadav Sanjay K. , Roy Rahul , Soin Arvinder S. 
Published: July 2018

AbstractBackgroundProsthetic vessel grafts are increasingly being used for anterior sector (AS) outflow reconstruction in right lobe living donor liver transplantation (RL‐LDLT) in view of easy availability and proper fit. The aim of the study was to analyze technique and outcomes of AS reconstruction using nonringed expanded polytetrafluoroethylene (ePTFE) grafts and compare outcomes with venous extension grafts.MethodsThis is a retrospective study of 437 consecutive RL‐LDLTs from January 2014 to August 2015. Vein (V) and ePTFE (alone or composite) were used alternatively or best fit for particular right lobe graft.ResultV graft was used in 200 recipients and ePTFE in 237 recipients with comparable preoperative donor and recipient characteristics. Cold ischemia time was significantly high in the ePTFE group. Postoperative recipient outcomes were comparable between the groups. The graft patency rate was comparable between the groups at different time intervals of follow‐up. However, 12‐month patency was low in those with multiple venous tributaries than with single outflow reconstruction ([V 90%, ePTFE 86.7%] vs [V 97.4%, ePTFE 95.2%]). No patient was re‐explored for graft blockage. There was no significant difference in 30‐day (V 92%, ePTFE 94.5%, P = 0.34), 90‐day (V 90%, ePTFE 90.7%, P = 0.87) and one‐year (V 87.5%, ePTFE 89%, P = 0.66) patient survival between the groups.ConclusionExpanded polytetrafluoroethylene gives equivalent patency and recipient outcomes with the added advantage of proper size match fit, allowing more complex AS reconstruction with ease without increased infection rate or associated complications.
Cranial ultrasound and neurophysiological testing to predict neurological outcome in infants born very preterm
Authors: Franckx Helen , Hasaerts Daniele , Huysentruyt Koen , Cools Filip 
Published: July 2018

AimInfants born preterm are at risk of cerebral palsy (CP) and motor or cognitive developmental delay. For clinicians, it is essential to know the relative predictive accuracy of the most commonly used neuroimaging and neurophysiological tests for the early prediction of adverse neurodevelopmental outcome. The aim of this study was to compare the accuracy of these tests in survivors of a population of infants born very preterm.MethodA retrospective cohort study was performed in 163 children born before 32 weeks gestational age. We compared the accuracy in predicting adverse neurodevelopmental outcome at the age of 2 years 6 months of early and late cranial ultrasound (CUS), magnetic resonance imaging, somatosensory evoked potentials after stimulation of the posterior tibial nerve, and electroencephalography by calculating positive and negative likelihood ratios.ResultsAn abnormal early CUS is the best predictor of the presence of CP (positive likelihood ratio 6.09), motor developmental delay (positive likelihood ratio 3.11), and cognitive developmental delay (positive likelihood ratio 5.66). Overall, negative likelihood ratios were poor, ranging between 0.49 and 0.98, meaning that a normal test result had only minimal influence on the probability of adverse neurological outcome.InterpretationNone of the diagnostic tests had a good performance in predicting future neurodevelopmental problems in infants born preterm. A normal test result provided very little clinically useful information.What this paper adds

An abnormal early cranial ultrasound (positive test result) is the best predictor of adverse neurodevelopmental outcome.

All negative results have poor predictive value of future neurodevelopmental problems.
Clinical and echocardiographic predictors of new‐onset atrial fibrillation in patients admitted with blunt trauma
Authors: Morsy Mohamed , Slomka Teresa , Shukla Anuj , Uppal Dipan , Bomb Ritin , Akinseye Oluwaseun A. , Koshy Santhosh K. G. , Garg Nadish 
Published: July 2018

BackgroundAtrial fibrillation (AF) is a common arrhythmia after trauma or burn injury; however, its predisposing factors are not well known. Moreover, little is known about its effect on mortality and other short‐term clinical outcomes.ObjectivesThis study is aimed at identifying risk factors for new‐onset AF in patients admitted with blunt trauma or burn injuries at a Level 1 academic trauma center, and to determine its effects on the short‐term clinical outcomes.MethodsThis case–control study compared patients with new‐onset AF with a cohort of patients without AF during the hospital stay after trauma or burn injury. Patients with prior AF or lack of transthoracic echocardiogram were excluded. Demographic, clinical factors including injury severity score and echocardiographic parameters were compared in both cohorts. Risks of short‐term clinical outcomes, namely persistent AF, new stroke, myocardial infarction, or death, were compared.ResultsOlder age, sepsis, CHADS2‐VASC score >1, larger left atrium (LA) size, left ventricular hypertrophy (LVH), and left ventricular diastolic dysfunction imposed a significant risk for new‐onset AF on univariate analysis. On multivariate, independent predictors of new‐onset AF were LA dilation and LVH. LA enlargement increased odds of new‐onset AF by 23‐fold (OR 23; CI: 5.7–92, P < 0.0001) and the presence of LVH increased the odds of new‐onset AF more than 20‐fold (OR 20.8; CI: 5–87, P < 0.0001).ConclusionsDilated LA and LVH are independent predictors of new‐onset AF in the patients with blunt trauma or burn. New‐onset AF did not confer increased risk for in‐hospital mortality.
Three‐dimensional speckle tracking echocardiography: Is it the magic wand in the diagnosis of subclinical myocardial dysfunction in children with type 1 diabetes mellitus?
Authors: El Razaky Osama , El Amrousy Doaa , Elrifaey Shaymaa , Elgendy Marwa , Ibrahim Wesam 
Published: July 2018

ObjectivesTo revaluate the role of three‐dimensional speckle tracking echocardiography (3D‐STE) in the evaluation of subclinical myocardial dysfunction in asymptomatic children with type 1 diabetes mellitus (DM).Patients and methodsFifty asymptomatic children with type 1 DM were included as a patient group. Fifty healthy children of matched age, sex, and weight served as a control group. Laboratory investigations in the form of complete blood count (CBC), liver function test, renal function test, complete blood lipid profile, glycosylated hemoglobin (HbA1c), fasting and 2 hours postprandial (PP) glucose levels, and cardiac troponin I (cTnT I) were drawn. Complete echocardiographic evaluation of the left ventricular (LV) function was performed in the form of conventional echo, 2D strain, tissue Doppler imaging (TDI), and 3D‐ STE.ResultscTnT I levels were significantly higher in the patient group than the control group, and this increase was significantly correlated with Hb A1c. Conventional echocardiography showed normal systolic and diastolic function of the LV. Diastolic (by TDI) as well as systolic functions of LV (by 4D LV quantification tool) were found to be significantly lower in patient group than control group. 3D‐STE examination showed that there was a significant decrease in all component of strain in patient group than control group and that decrease correlated well with 4D LV EF but did not correlate with the duration of DM. There was a significant negative correlation between longitudinal strain and the control of DM.Conclusion3D‐STE is a good tool for prediction of early cardiac dysfunction in asymptomatic children with type 1 DM.
Suppression of hepatitis B surface antigen production by combination therapy with nucleotide analogues and interferon in children with genotype C hepatitis B virus infection
Authors: Tajiri Hitoshi , Takano Tomoko , Tanaka Yasuhito , Murakami Jun , Brooks Stephen 
Published: July 2018

AimSustained suppression of hepatitis B surface antigen (HBsAg) production after interferon (IFN) treatment has not been reported for children with genotype C chronic hepatitis B virus (HBV) infection, which is prevalent in Asia. Among children with hepatitis B envelope antigen‐positive genotype C chronic HBV infection, we compared the efficacy of combination therapy with nucleotide analogues and IFN‐α in 11 children with 12 historical cases treated with IFN monotherapy.MethodsThe combination of lamivudine and conventional IFN‐α was introduced for the first three patients; the other eight patients were treated with entecavir and pegylated IFN.ResultsDemographic factors as well as baseline HBsAg titers and HBV‐DNA levels were similar between the two groups. In the combination therapy group, viral loads were suppressed in 9/11 to below 4.0 log copies/mL both at the end of the therapy (EOT) and at 6 months after EOT. In contrast, in the IFN monotherapy group, suppression of viral loads was observed in 2/12 and 3/12 at EOT and at 6 months after EOT, respectively. In the combination therapy group, HBsAg titers dropped from 4.03 at pretreatment to 2.91 log IU/mL at 6 months after EOT with 4/11 showing a drop to below 1000 IU/mL (one patient achieved HBsAg clearance). In contrast, the amount of HBsAg did not change during the corresponding periods in the IFN monotherapy group.ConclusionsOur preliminary results suggest that combination therapy might be effective in the suppression of HBsAg production as well as HBV‐DNA production for children with genotype C chronic HBV infection.
Optimization of borosilicate glass/CaTiO3‐TiO2 composite via altering prefiring temperature and particle size
Authors: Ren Luchao , Luo Xianfu , Xia Yunsheng , Hu Yongkang , Zhou Hongqing 
Published: July 2018

AbstractLow‐temperature co‐fired ceramic (LTCC) with middle permittivity is very crucial to the miniaturization of components. Based on our previous study on the glass/CaTiO3‐TiO2 composite, prefiring temperature and particle size of CaTiO3‐TiO2 ceramic were optimized in this study to promote the performance of the composites. Comparing with our previous study, after being sintered with 50 wt% glass at 875°C, CaTiO3‐TiO2 ceramic prefired at 1275°C with particle size of 3.38 μm showed excellent properties of sintering density = 3.33 g/cm3, εr = 30.2, tan δ = 0.0005 (7 GHz). In addition, surface roughness of green tapes was also improved after optimization. The material has a good chemical stability and shrinkage matching with silver, making it a very promising candidate material for LTCC applications.
The Saudi Arabian 2030 vision and the nursing profession: the way forward
Authors: AL‐Dossary R.N. 
Published: July 2018

AimTo examine the outlook of the Saudi Arabian nursing profession in relation to the recently launched Kingdom 2030 Vision.IntroductionNursing in Saudi Arabia has advanced noticeably in education and clinical practice, but challenges remain in building and sustaining a Saudi nursing profession and workforce.BackgroundHealth care in Saudi Arabia is currently experiencing transformation because of population and economic growth. These transformations have been influenced by the Saudi Arabian 2030 Vision.Sources of evidenceA literature review here examines the progress in transforming the nursing profession in Saudi Arabia. Relevant studies published between 2001 and 2017 were identified, using databases such as Medline, PubMed and PsychInfo.ResultsNineteen studies reporting challenges and opportunities that the nursing profession faces in Saudi Arabia were included.DiscussionThe nursing profession in Saudi Arabia faces challenges from nursing shortages, underdeveloped nursing education and unclear scope of practice. However, the new 2030 Vision offers many opportunities for social and economic transformation.ConclusionEffective strategies must be implemented to accommodate the new outlook the 2030 Saudi Vision in order to advance the nursing profession and to improve healthcare delivery in Saudi Arabia.Implications for nursing and nursing policyNursing policymakers urgently need to improve nursing care in Saudi Arabia by addressing the nursing shortage, generating strategies to improve nursing education and establishing scope of practice guidelines. These critical issues must be addressed with the context of the 2030 Vision.
Ten‐year changes in ambulatory blood pressure: The prognostic value of ambulatory pulse pressure
Authors: Balietti Paolo , Spannella Francesco , Giulietti Federico , Rosettani Giulia , Bernardi Beatrice , Cocci Guido , Bonfigli Anna R. , Sarzani Riccardo 
Published: July 2018

Blood pressure (BP) changes and risk factors associated with pulse pressure (PP) increase in elderly people have rarely been studied using ambulatory blood pressure monitoring (ABPM). The aim is to evaluate 10‐year ambulatory blood pressure (ABP) changes in older hypertensives, focusing on PP and its associations with mortality. An observational study was conducted on 119 consecutive older treated hypertensives evaluated at baseline (T0) and after 10 years (T1). Treatment adherence was carefully assessed. The authors considered clinical parameters at T1 only in survivors (n = 87). Patients with controlled ABP both at T0 and T1 were considered as having sustained BP control. Change in 24‐hour PP between T0 and T1 (Δ24‐hour PP) was considered for the analyses. Mean age at T0: 69.4 ± 3.7 years. Females: 57.5%. Significant decrease in 24‐hour, daytime, and nighttime diastolic BP (all P < .05) coupled with an increase in 24‐hour, daytime, and nighttime PP (all P < .05) were observed at T1. Sustained daytime BP control was associated with lower 24‐hour PP increase than nonsustained daytime BP control (+2.23 ± 9.36 vs +7.79 ± 8.64 mm Hg; P = .037). The association between sustained daytime BP control and Δ24‐hour PP remained significant even after adjusting for age, sex, and 24‐hour PP at T0 (β=0.39; P = .035). Both 24‐hour systolic BP and 24‐hour PP at T0 predicted mortality (adjusted HR 1.07, P = .001; adjusted HR 1.25, P < .001, respectively). After ROC comparison (P = .001), 24‐hour PP better predicted mortality than 24‐hour systolic BP. The data confirm how ABP control affects vascular aging leading to PP increase. Both ambulatory PP and systolic BP rather than diastolic BP predict mortality in older treated hypertensives.
The association between paraoxonase 1 activity and the susceptibilities of diabetes mellitus, diabetic macroangiopathy and diabetic microangiopathy
Authors: Wu Diling , Wu Chenfang , Zhong Yanjun 
Published: July 2018

AbstractWe carried out this meta‐analysis to explore the influence of paraoxonase 1 activity on the susceptibility of diabetes mellitus (DM), diabetic macroangiopathy and diabetic microangiopathy. Relevant studies were identified from PubMed, Web of Science and CNKI without language limitation, following the inclusion and exclusion criteria. Statistical analyses were implemented with the STATA 12.0 statistical software. Thirty‐six case‐control studies were included in the meta‐analyses, in which 35 for the association between paraoxonase 1 activity and DM risk, 8 for diabetic macroangiopathy and 7 for diabetic microangiopathy. Paraoxonase 1 activity was significantly associated with the susceptibility of DM in pooled population (SMD = −1.37, 95% CI = −1.79 ∼ −0.96, P = .000), and Asians (SMD = −2.00, 95% CI = −2.56 ∼ −1.44, P = .000), but not in non‐Asians (SMD = −0.44, 95% CI = −0.91 ∼ 0.03, P = .069). However, marked heterogeneity was existed (I2 = 98.10%, P = .000) and subgroup analyses failed to investigate the sources of heterogeneity. Then, meta‐regression was performed and found that ethnicity could explain the observed between‐study heterogeneity (P = .002). Meanwhile, significant associations were found between paraoxonase 1 activity and diabetic macroangiopathy (SMD = −1.06, 95% CI = −1.63 ∼ −0.48, P = .000) and diabetic microangiopathy (SMD = −0.72, 95% CI = −1.32 ∼ −0.13, P = .018). In conclusion, paraoxonase 1 activity plays important roles in the risk of DM, diabetic macroangiopathy and microangiopathy with ethnicity differences. Further studies with large sample and well design are needed to confirm these results.
Long‐term treatment costs of chronic periodontitis patients in Germany
Authors: Schwendicke Falk , Engel Anne Sophie , Graetz Christian 
Published: July 2018

AbstractAimWe assessed the long‐term costs for treating chronic periodontitis (CP) patients.MethodsA cohort of compliant CP patients was retrospectively evaluated. Costs for active periodontal therapy (APT, including scaling and root planning, open flap debridement, root resections) and supportive periodontal therapy (SPT including periodontal, restorative, endodontic, prosthetic and surgical treatments) were estimated from a mixed payer perspective in Germany. The impact of tooth‐ and patient‐level factors on annual costs was assessed using mixed‐modelling.ResultsTwo hundred and seventy‐three patients (mean ± SD age: 49.6 ± 8.8 years), with 24.3 ± 4.5 teeth, were included. Mean follow‐up was 18.7 ± 5.7 years. Total treatment costs per patient and per tooth were 6,146 ± 2,236 and 222 ± 98 Euro, respectively. Costs were generated mainly by periodontal therapy and during SPT. Annualized patient‐ and tooth‐level costs were 348 ± 159 and 12.4 ± 5.7 Euro, respectively. Annual costs increased significantly in older patients, regular attenders, those with fewer teeth (<24) at baseline and teeth with higher probing pocket depths or mobility 3 at baseline.ConclusionsAnnual costs for treating CP patients were lower than those found for aggressive periodontitis patients. Regular attendance and having more severe periodontitis came with higher costs per year.
Comparative evaluation of subgingivally‐delivered 1% metformin and Aloe vera gel in the treatment of intrabony defects in chronic periodontitis patients: A randomized, controlled clinical trial
Authors: Kurian Ida G. , Dileep Pankaj , Ipshita Sahu , Pradeep Avani R. 
Published: July 2018

AbstractAimThe aim of the current study was to explore the effectiveness of locally‐delivered 1% metformin (MtF) and Aloe vera (AV) gel as an adjunct to scaling and root planning (SRP) in the treatment of intrabony defects in chronic periodontitis patients.MethodsA total of 90 volunteers were randomly assigned to three treatment groups: (a) SRP + placebo gel; (b) SRP + 1% MtF gel; and (c) SRP + AV gel. Clinical parameters, including gingival index (GI), bleeding on probing (BoP), pocket probing depth (PPD), and clinical attachment level (CAL), were recorded at baseline, and 6 and 12 months. The radiological assessment of bone defect fill was done at 6 and 12 months.ResultsGI, BoP, PPD, and CAL improved in all the groups; however, the mean PPD reduction, CAL gain, and percentage of bone fill was found to be greater in the MtF and AV groups than the placebo group at all visits.ConclusionLocal delivery of 1% MtF and AV gel stimulates a significant PPD reduction, CAL gain, and improved bone fill and regeneration when compared with placebo gel. Results were significantly better with the use of 1% MtF gel than AV gel.